ArticlePDF Available

Abstract

Antibiotics have been effective in treatment of infectious diseases, but resistance to these drugs has led to the severe infectious diseases. In recent years, medicinal herbals have been used for the prevention and protection against infectious diseases. Thymol and carvacrol are active ingredients of family lamiaceae. These components have antibacterial and antifungal effects. In this review, we survey antimicrobial properties of, carvacrol and thymol. Available data from different studies (microbiological, retrieve from PubMed and Scopus databases) about antimicrobial affects carvacrol and thymol was evaluated. carvacrol and thymol can inhibit growth of both Gram positive and Gram negative bacteria. These compounds have antifungal and antibiofilm effects. Thymol and carvacrol can be applied as an alternative antimicrobial agent against antibiotic-resistant pathogenic bacteria. Thus, it is recommended potential medical use of thymol and carvacrol, but more research must be done on toxicity and side effects issue.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
Carvacrol and thymol: strong antimicrobial agents
against resistant isolates
Mohammad Y. Memar
a,b
, Parisa Raei
c
, Naser Alizadeh
b,d
,
Masoud Akbari Aghdam
a
and Hossein Samadi Kafil
d
Antibiotics have been effective in treatment of infectious diseases, but resistance to
these drugs has led to the severe consequences. In recent years, medicinal herbs have
been used for the prevention and protection against infectious diseases. Thymol and
carvacrol are active ingredients of family Lamiaceae; these components have anti-
bacterial and antifungal effects. In this review, we survey antimicrobial properties of
carvacrol and thymol. Available data from different studies (microbiological, retrieve
from PubMed, and Scopus databases) about antimicrobial affects carvacrol and thymol
was evaluated. Carvacrol and thymol can inhibit the growth of both gram-positive and
gram-negative bacteria. These compounds have antifungal and antibiofilm effects.
Thymol and carvacrol can also be applied as an alternative antimicrobial agent against
antibiotic-resistant pathogenic bacteria. Thus, thymol and carvacrol are recom-
mended for potential medical use; however, more research is required on toxicity
and side-effects of the compounds.
Copyright ß2017 Wolters Kluwer Health, Inc. All rights reserved.
Reviews in Medical Microbiology 2017, 28:6368
Keywords: antibacterial, antibiofilm, antifungal, carvacrol, thymol
Introduction
Infectious diseases are common reasons of morbidity and
mortality in the world [1]. Introduction of antibiotics
have had a consequence not only on the management of
infections but also on society by changing morbidity and
mortality [2]. However, the abuse of these compounds has
led to the emergence and increasing of multidrug-
resistant pathogens [3]. The situation is deteriorated by
the increasing the number of antibiotic-resistant patho-
gens and potential to endure after exposure to
antimicrobial agents [4]. As no new drugs have been
introduced to manage antibiotic-resistant pathogens, and
as it seems doubtful that any novel agents will be
established presently, clinicians may become obliged to
administrate some drugs regardless of their complications
[5]. Hence, antibiotic-resistant pathogens are public
health crisis and the need to explore and identify new
compounds with antibacterial properties without toxic
effects on human cells is obvious [6].
Plants are one source of the compounds with anti-
microbial activity that provides options of novel
alternative drugs for microbial disease [7]. Essential oils
derived from plants are one of the most important
agricultural products with antimicrobial property [8].
About 3000 essential oils produced by at least 2000 plant
species, which about 300 of them are significant from the
marketing viewpoint [9]. Essential oils and their
constituent small molecules exhibit excellent medicinal
properties and hence may be used against infectious and
noninfectious diseases [10]. Essential oils are definite as
any volatile oil(s) that have strong aromatic components
and that give characteristic odor, flavor, or smell to a
plant. These are the byproducts of plant metabolism and
are frequently referred to as volatile plant secondary
metabolites. Essential oils are found in glandular hairs or
secretory cavities of plant-cell wall and are present as
droplets of juice in the leaves, stems, bark, flowers, roots,
and/or fruits in different plants [11]. Carvacrol and
thymol are the major constituents of the essential oils,
a
Infectious and Tropical Disease Research Center,
b
Student Research Committee,
c
Drug Applied Research Center, and
d
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Correspondence to Hossein Samadi Kafil, PhD, Assistant Professor, Drug Applied Research Center, Tabriz University of Medical
Sciences, Tabriz, Iran.
Tel: +98 9127184735; fax: +98 4133364661; e-mail: Kafilhs@tbzmed.ac.ir
Received: 21 October 2016; revised: 2 February 2017; accepted: 7 February 2017
DOI:10.1097/MRM.0000000000000100
ISSN 0954-139X Copyright Q2017 Wolters Kluwer Health, Inc. All rights reserved. 63
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
which belong to the Lamiaceae family of plants including
oregano and thyme [12]. In this study, we review
antimicrobial effects of carvacrol and thymol.
Traditional application
The ancient Egyptians used thymol and carvacrol as
protective agents to preserve the mummies [13]. They
were also used as an active additive in food flavoring,
perfumes, cosmetics, mouthwash, and some of them have
been made for massaging the joints and to treat nail fungi
as topical ointments. Drugs formulated from these
compounds were administered to care for infections of
the mouth and throat and prevent of gingivitis [14].
Thymol
Thymol (also known as 2-isopropyl-5-methylphenol)
(Fig. 1), a phenolic compound present in essential oils, is a
natural monoterpene and carvacrol isomer that extracted
from thyme and the other kinds of plants [15]. Thymol is
less water soluble at neutral pH, but it is as well soluble in
some organic solvents and alcohols [16]. It has been
observed its antioxidant, antispasmodic, antimicrobial,
and anti-inflammatory property [17]. It is a p-cymene
derivative compound and is also identified for the
antiseptic and antimicrobial effects [18]. Some studies
have reported the usage of thymol for anticancer property
[19]. The antioxidant effects of thymol and carvacrol have
been confirmed in several studies, suggesting their
administration as nutritious elements in the improvement
of novel functional foods [20]. Thymol protective
nature against caries and plaques allures the field of
dental drugs [21].
Carvacrol
Carvacrol (5-isopropyl-2-methylphenol), (Fig. 1), is also
monoterpene that found in many plant species such as
thyme and with greater amount in oregano [22].
Carvacrol is significant component of essential oils and
recently has attracted much attention as a result of its
biological properties, such as a wide spectrum of
antimicrobial activity. Because carvacrol exhibits strong
antioxidative properties and both hydrophobic properties
associated with the substituted aromatic ring and
hydrophilic properties associated with the phenolic
OH group, numerous studies report its antioxidative,
anti-inflammatory, antibacterial, antifungal, antiproto-
zoal, anticarcinogenic, antidiabetic, antinociceptive,
cardioprotective, and neuroprotective properties [23].
Antibacterial effect of thymol and
carvacrol
Several studies were reported antibacterial effects of
thymol alone or in combination with other substance
such as carvacrol [24]. These compounds can inhibit
growth of both gram-positive and gram-negative bacteria
[24]. Low toxicity and pleasant smell as well as taste of
thymol show that this material can be used as an additive
to prevent bacterial spoilage [25]. Trombetta et al. [26]
report the antimicrobial efficacy of thymol against
Staphylococcus aureus and Escherichia coli. Some researchers
speculated that the antibacterial mechanism of thymol
may consequence, at least partly, from a perturbation of
the lipid fraction of the bacterial plasma membrane,
resulting in changes of membrane permeability and in the
escape of intracellular content [27,28]. Lambert, et al.
exhibited antibacterial effect of thymol and carvacrol
against Pseudomonas aeruginosa and S. aureus as a result of
disruption in membrane integrity, which further affects
the pH homeostasis and balance of inorganic ions [27].
Therefore, antibacterial property of carvacrol and thymol
is dependent to their capability to permeabilize,
depolarize, and disruption of the cytoplasmic membrane.
Gas chromatographic mass spectrometric examination
indicated thymol is major essential oil of Monarda punctata.
The results of study carried by Li et al. [29] indicated that
Streptococcus pyogenes,E. coli, and Streptococcus pneumonia
were the most susceptible to thymol, whereas methicillin-
resistant S. aureus was reported to be the most resistant
to the essential oil with relatively higher Minimum
Inhibitory Concentration (MIC) and Minimum
bactericidal concentration (MBC) values. The disk
diffusion method data show thymol is most effective
against Brochothrix thermosphacta (Inhibition Zone:
39.7 mm) followed by Listeria monocytogenes and Salmo-
nella thyphimurium (Inhibition Zone: 35.6 and 33.3 mm,
respectively). The MIC and MBC values (0.25 and
0.5 mg/ml, respectively) were the same for L. mono-
cytogenes,S. thyphimurium, and E. coli O157:H7.
Pseudomonas fluorescens was the least inhibited by thymol
(MIC and MBC ranging from 1 to 1.5 mg/ml). These
components could be probable options to be applied as
64 Reviews in Medical Microbiology 2017, Vol 28 No 2
Fig. 1. Chemical structure of thymol and carvacrol.
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
natural alternatives for further usage in food conservation
to hold up or inhibit the bacterial increase and for
protection and to expand the shelf existence of the food
products. However, the verification of antibacterial
effects and organoleptic impact of these essential oils in
foodstuffs require assessing [30]. Results of several studies
were confirmed bactericidal effects of thymol and
carvacrol against of pathogens and food spoilage bacteria
(Table 1) [24,3139].
The antibacterial efficacy of carvacrol and thymol in
combination with other antibacterial compounds on
gram-negative and gram-positive organism were eval-
uated in some studies. The results of these studies will be
affected by the methods for detection of synergy effects.
For example Hamoud et al. [40], reported checkerboard
data indicate indifferent interaction against gram-positive
and synergy against gram-negative bacteria, whereas
time-kill analyses advocate synergistic achievement in
diverse combinations against both types of bacteria.
Combinations of thymol and carvacrol with antibacterial
(azithhromycin, clarithromycin, minocycline, and tige-
cycline) using checkerboard indicted achievement a
synergism in the great majority of cases [41]. Thymol and
carvacrol were found to be highly efficient in increasing
the susceptibility of S. typhimurium to ampicillin,
tetracycline, penicillin, bacitracin, erythromycin, and
novobiocin and resistance of S. pyogenes to erythromycin
[24]. On the basis of these data, the authors recommended
that thymol in combination with specific antimicrobial
drugs may be an efficient alternative option to treat
infections.
Effect of thymol and carvacrol on biofilm
formation
Biofilm biomass is a mixture of exopolysaccharides,
proteins, DNA, and extracellular matrix that has the
stabilizing role of biofilm construction [42]. Bacteria in a
biofilm are much more resistant to antibiotics than to
planktonic status [43]. The plant derivatives can effect on
microbial biofilms [44]. Several studies described thymol
and carvacrol inhibited growth of preformed biofilm and
interfered with biofilm formation during planktonic
growth [45,46]. Nostro et al. [46] reported carvacrol and
thymol attenuated biofilm formation of S. aureus and
Staphylococcus epidermidis strains on polystyrene microtitre
plates and they suggested these oils repressed expansion of
Carvacrol and thymol: strong antimicrobial agents Memar et al. 65
Table 1. Results of varies study that assessed antimicrobial effects of thymol and carvacrol.
Compound Microorganism Main findings References
Thymol, carvacrol,
cinnamaldehyde, and
eugenol alone or
combined
Streptococcus mutans
ATCC25175
Use of eugenol and thymol or eugenol and carvacrol
combinations would be suitable in the management of
oral infections
[31]
S. sanguis,S. mitis, and S. milleri
Peptostreptococcus anaerobius
ATCC 4956, Prevotella buccae,
P. oris, and P. intermedia
Cinnamaldehyde,
thymol, and carvacrol
alone or their
combinations
S. typhimurium MIC of cinnamaldehyde, thymol, and carvacrol for
S. typhimurium were 200, 400, and 400 mg/l,
respectively. By their paired combinations, MIC of
cinnamaldehyde, thymol and carvacrol could be
decreased from 200, 400, and 400 mg/l to 100, 100, and
100 mg/l, respectively
[32]
Oregano oil, carvacrol,
and thymol
Methicillin-susceptible and
methicillin-resistant
staphylococci (MSS and MRS)
All S. aureus and S. epidermidis strains reported susceptible
to these compound with no significant difference
between MRS and MSS strains
[33]
Carvacrol and thymol E. coli Carvacrol and thymol could inhibit the growth of E. coli.
The antibacterial property was related to their capacity to
permeabilize and depolarize the bacterial membrane
[34]
Lippia sidoides and
thymol
Enterococcus faecalis Thymol kill microorganisms present in biofilms [35]
Thymol L. monocytogenes Thymol could potentially be applied to control L.
monocytogenes biofilms in food processing
[36]
Carvacrol and thymol Shigella sonnei and S. flexneri Antibacterial effects of thymol and carvacrol against
Sheigella spp.
[37]
Thymol C. albicans Thymol may be used as a potential antifungal therapy in the
future
[38]
Carvacrol and thymol P. digitatum and P. italicum The application of these essential oils in the citrus packing
lines could be considered as appropriate alternatives to
reduce the use of synthetic fungicides
[39]
Eugenol, carvacrol,
thymol and
cinnamaldehyde
Tetracycline-resistant S.
Typhimurium and E. coli,
penicillin-resistant S. aureus
and erythromycin-resistant S.
pyogenes
Natural antimicrobials were able to significantly reduce the
MIC of antibiotics in a different group of resistant bacteria
[24]
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
preformed biofilm and obstructed with the biofilm
development during planktonic phase. El Abed et al. [47]
also described anti-adherence and antibiofilm effects of
terpenes and pointed out the excellent effectiveness of
eugenol, carvone, and carveol, which could characterize
candidates in the management of P. aeruginosa biofilm.
Thymol can also prevent the first stages of biofilm
formation and interfering with the formation of mature
biofilms as a result of the inhabitation of metabolic
activity for biofilms. All of these events may lead to major
membrane and blockage the production of viable
filamentous forms during the early steps of biofilm
formation. As biofilms are multifactorial event, the several
mechanisms of thymol (terpenes) perhaps effect on
diverse stages in their development [48].
Antifungal effect by thymol and carvacrol
Direct antifungal agents resistance is still a chief unease
when antifungal treatment failure is considered [49].
There are limits antifungal drugs available for treatment,
drug-resistant strains are also evidence of biofilm
infections and side-effects of prescription drugs will have
problems in the prevention and treatment of fungal
infections [50]. Several studies described antifungal effects
of thymol and carvacrol against fungal pathogens.
Antifungal effect of thymol and carvacrol investigated
against Penicillium digitatum and Penicillum italicum. Both
essential oils were effective in inhibiting fungal growth;
thymol was more effective than carvacrol [39].
Guo et al. [51] indicated antifungal activity of thymol
against clinical isolates of fluconazole susceptible and
nonsusceptible Candida albicans and high percentage of
synergism effects of thymol in combination with
amphotericin B.
Thymol and carvacrol because of the restrain of ergosterol
biosynthesis and the disturbance of membrane totality
shows potent fungicidal efficacy against Candida isolates
[52]. Effective fungicidal properties of carvacrol and
thymol against different plant pathogens were also
formerly reported by Kordali et al. [53].
Development of herbicides helps reduce factors such as
pollution and environmental degradation; in this regard,
natural herbicides can be effective. Essential oils and
monoterpenes compounds showed antifungal activity in
the treatment of mucormycosi [54,55].
Thymol is lipophilic compound, that alone or with
carvacrol, can change the cell membrane fluidity and
permeability [56]. In addition to this, the compound can
changes the cell membrane in fungi such as C. albicans by
the affect the function of the cell membrane enzymes that
catalyzes the synthesis of the cell wall polysaccharide
compounds such as b-glucan and inhibit the growth of
cells [57,58]. The results of electron microscopy showed
that thymol and carvacrol change the morphogenesis of
the envelope of C. albicans [58].
Carvacrol was also effective in reducing the growth of
Botrytis cinerea in berry and grapes; in grapes, 97%
inhibition was related to the higher doses of carvacrol
[59,60]. In addition to this, carvacrol was effective in
reducing the spore germinates and mycelium growth of
B. cinerea inoculated in grapes [59].
Other researchers showed the effect of monoterpenoid-
son the conidial germination and mycelial growth of B.
cinerea [61]. Also, Tsao and Zhou [61] reported that
0.25 mg/ml of thymol had an inhibitory effect on the
increase of mycelium of Monilinia fructicola, also on the
solid media, was 100% inhibited conidial germination of
the bacteria.
Toxicity issue
Essential oils affect the various active molecules in the cell
for different purposes, that, main purpose is the
cytoplasmic membrane [62]. Disruption of the per-
meability of the cell membrane leads to the loss of cell
function such as the electron transport chain, also affected
the eukaryotic cells [63]. Toxicity to eukaryotic cells is
responsible for undesirable side-effects for a host, such as
inflammation, corrosion, cell sensitivity, acute toxicity to
organs, and limits the use of essential oils as medicinal use
[52]. It is difficult to detect the toxicity of essential oils
because the toxicity varies based on the compounds and
depends on various factors [64]. A study showed that
thymol and carvacrol had the most toxic in concen-
trations of 36 –49 mg/l, which are less toxic than some
combination of essential oils [65]. There is less risk of
accumulation of body tissues. Therefore, it is suggested
possible medical use thymol and carvacrol, but more
research must be done on this issue.
Conclusion
Several studies have shown antibacterial and antifungal
property of the thymol and carvacrol. Thymol and
carvacrol can be applied as an alternative antimicrobial
agent against antibiotic-resistant pathogenic bacteria and
C. albicans. It is necessary for further precise detection of
thymol and carvacrol safety to determine the optimal dose
of these substances for human cells. Results of various
studies proposed replace of traditional medicines instead
of synthetic drugs, which has more side-effects. In this
review, reported information about the effects of
antibacterial, antifungal, and antibiofilm thymol and
66 Reviews in Medical Microbiology 2017, Vol 28 No 2
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
carvacrol that provides a better view about the thymol and
carvacrol. More studies using bacterial strains isolated
from patients treated with these compounds needs to
be done.
Acknowledgements
This study was supported by Drug Applied Research
Center, Tabriz University of Medical Sciences, Tabriz,
Iran.
Conflicts of interest
The authors declare no conflicts of interest.
References
1. World Health Organization. World health statistics 2010.
Geneva, Switzerland: World Health Organization; 2010.
2. Zaffiri L, Gardner J, Toledo-Pereyra LH. History of antibiotics. From
salvarsan to cephalosporins. J Investig Surg 2012; 25:67–77.
3. English BK, Gaur AH. The use and abuse of antibiotics and the
development of antibiotic resistance. Hot topics in infection
and immunity in children VI.Springer; 2010. pp. 73–82.
4. Norrby SR, Nord CE, Finch R. Lack of development of new
antimicrobial drugs: a potential serious threat to public health.
Lancet Infect Dis 2005; 5:115–119.
5. Falagas ME, Kasiakou SK, Saravolatz LD. Colistin: the revival of
polymyxins for the management of multidrug-resistant gram-ne-
gative bacterial infections. Clin Infect Dis 2005; 40:1333–1341.
6. Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon
BP, et al.A new antibiotic kills pathogens without detectable
resistance. Nature 2015; 517:455–459.
7. Basri DF, Xian LW, Abdul Shukor NI, Latip J. Bacteriostatic
antimicrobial combination: antagonistic interaction between
epsilon-viniferin and vancomycin against methicillin-resistant
Staphylococcus aureus.BioMed Res Int 2014; 2014: Article
ID 461756.
8. Oke F, Aslim B, Ozturk S, Altundag S. Essential oil composition,
antimicrobial and antioxidant activities of Satureja cuneifolia
Ten. Food Chem 2009; 112:874–879.
9. Hussain AI. Characterization and biological activities of essen-
tial oils of some species of Lamiaceae. Faisalabad: University of
Agriculture; 2009.
10. Raut JS, Karuppayil SM. A status review on the medicinal
properties of essential oils. Industrial Crops Products 2014;
62:250–264.
11. Koul O, Walia S, Dhaliwal G. Essential oils as green pesticides:
potential and constraints. Biopestic Int 2008; 4:63–84.
12. Daferera DJ, Tarantilis PA, Polissiou MG. Characterization of
essential oils from Lamiaceae species by Fourier transform
Raman spectroscopy. J Agric Food Chem 2002; 50:5503–5507.
13. Venu S, Naik D, Sarkar S, Aravind UK, Nijamudheen A,
Aravindakumar C. Oxidation reactions of thymol: a pulse radi-
olysis and theoretical study. JPhysChemA2013; 117:291–299.
14. Szyszkowska A, Koper J, Szczerba J, Pulawska M, Zajdel D. The
use of medicinal plants in dental treatment. Structure 2010;
56:97–107.
15. Wattanasatcha A, Rengpipat S, Wanichwecharungruang S.
Thymol nanospheres as an effective antibacterial agent. Int J
Pharm 2012; 434:360–365.
16. Darre M, Kollanoor-Johny A, Venkitanarayanan K, Upadhyaya
I. Practical implications of plant-derived antimicrobials in
poultry diets for the control of Salmonella enteritidis.J Appl
Poultry Res 2014; 23:340–344.
17. Deb DD, Parimala G, Devi SS, Chakraborty T. Effect of thymol
on peripheral blood mononuclear cell PBMC and acute pro-
myelotic cancer cell line HL-60. Chem Biol Interact 2011;
193:97–106.
18. Shapiro S, Guggenheim B. The action of thymol on oral bac-
teria. Oral Microbiol Immunol 1995; 10:241–246.
19. An dersen A. Final report on the safety assessment of sodium p-
chloro-m-cresol, p-chloro-m-cresol, chlorothymol, mixed
cresols, m-cresol, o-cresol, p-cresol, isopropyl cresols,
thymol, o-cymen-5-ol, and carvacrol. Int J Toxicol 2005;
25:29–127.
20. Rubio
´L, Motilva M-J, Romero M-P. Recent advances in biolo-
gically active compounds in herbs and spices: a review of the
most effective antioxidant and anti-inflammatory active prin-
ciples. Crit Rev Food Sci Nutr 2013; 53:943–953.
21. Chauhan AK, Jakhar R, Paul S, Kang SC. Potentiation of macro-
phage activity by thymol through augmenting phagocytosis. Int
Immunopharmacol 2014; 18:340–346.
22. Burt S. Essential oils: their antibacterial properties and poten-
tial applications in foods: a review. Int J Food Microbiol 2004;
94:223–253.
23. Friedman M. Chemistry and multibeneficial bioactivities of
carvacrol (4-isopropyl-2-methylphenol), a component of es-
sential oils produced by aromatic plants and spices. J Agric
Food Chem 2014; 62:7652–7670.
24. Palaniappan K, Holley RA. Use of natural antimicrobials to
increase antibiotic susceptibility of drug resistant bacteria. Int J
Food Microbiol 2010; 140:164–168.
25. Tisserand R, Young R. Essential oil safety: a guide for healthcare
professionals.Elsevier Health Sciences; 2013.
26. Trombetta D, Castelli F, Sarpietro MG, Venuti V, Cristani M,
Daniele C, et al.Mechanisms of antibacterial action of three
monoterpenes. Antimicrob Agents Chemother 2005; 49:2474–
2478.
27. Lambert R, Skandamis PN, Coote PJ, Nychas GJ. A study of the
minimum inhibitory concentration and mode of action of
oregano essential oil, thymol and carvacrol. J Appl Microbiol
2001; 91:453–462.
28. de Souza EL, de Barros JC, de Oliveira CEV, da Conceic¸a
˜oML.
Influence of Origanum vulgare L. essential oil on enterotoxin
production, membrane permeability and surface characteris-
tics of Staphylococcus aureus.Int J Food Microbiol 2010;
137:308–311.
29. Li H, Yang T, Li F-Y, Yao Y, Sun Z-M. Antibacterial activity
and mechanism of action of Monarda punctata essential oil
and its main components against common bacterial patho-
gens in respiratory tract. Int J Clin Exp Pathol 2014; 7:7389–
7398.
30. Mith H, Dure R, Delcenserie V, Zhiri A, Daube G, Clinquart A.
Antimicrobial activities of commercial essential oils and their
components against food-borne pathogens and food spoilage
bacteria. Food Sci Nutr 2014; 2:403–416.
31. Didry N, Dubreuil L, Pinkas M. Activity of thymol, carvacrol,
cinnamaldehyde and eugenol on oral bacteria. Pharma Acta
Helv 1994; 69:25–28.
32. Zhou F, Ji B, Zhang H, Jiang H, Yang Z, Li J, et al.The
antibacterial effect of cinnamaldehyde, thymol, carvacrol
and their combinations against the foodborne pathogen Sal-
monella typhimurium.J Food Safety 2007; 27:124–133.
33. Nostro A, Blanco AR, Cannatelli MA, Enea V, Flamini G, Morelli
I, et al.Susceptibility of methicillin-resistant staphylococci to
oregano essential oil, carvacrol and thymol. FEMS Microbiol
Lett 2004; 230:191–195.
34. Xu J, Zhou F, Ji BP, Pei RS, Xu N. The antibacterial mechanism
of carvacrol and thymol against Escherichia coli.Lett Appl
Microbiol 2008; 47:174–179.
35. Veras H, Rodrigues F, Botelho MA, Menezes I, Coutinho H, da
Costa J. Antimicrobial effect of Lippia sidoides and thymol on
Enterococcus faecalis biofilm of the bacterium isolated from
root canals. Sci World J 20142014.
36. Upadhyay A, Upadhyaya I, Kollanoor-Johny A, Venkitanaraya-
nan K. Antibiofilm effect of plant derived antimicrobials on
Listeria monocytogenes.Food Microbiol 2013; 36:79–89.
37. Bagamboula C, Uyttendaele M, Debevere J. Inhibitory effect of
thyme and basil essential oils, carvacrol, thymol, estragol,
linalool and p-cymene towards Shigella sonnei and S. flexneri.
Food Microbiol 2004; 21:33–42.
38. Shu C, Sun L, Zhang W. Thymol has antifungal activity against
Candida albicans during infection and maintains the innate
immune response required for function of the p38 MAPK
signaling pathway in Caenorhabditis elegans.Immunol Res
2016:1–12.
Carvacrol and thymol: strong antimicrobial agents Memar et al. 67
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
39. Pe
´rez-Alfonso C, Martı´nez-Romero D, Zapata P, Serrano M, Valero
D, Castillo S. The effects of essential oils carvacrol and thymol on
growth of Penicillium digitatum and P. italicum involved in lemon
decay. Int J Food Microbiol 2012; 158:101–106.
40. Hamoud R, Zimmermann S, Reichling J, Wink M. Synergistic
interactions in two-drug and three-drug combinations (thymol,
EDTA and vancomycin) against multi drug resistant bacteria
including E. coli.Phytomedicine 2014; 21:443–447.
41. Jesus F, Ferreiro L, Bizzi K, Loreto E, Pilotto M, Ludwig A, et al.In
vitro activity of carvacrol and thymol combined with antifun-
gals or antibacterials against Pythium insidiosum.J Med Mycol
2015; 25:e89–e93.
42. Davey ME, O’toole GA. Microbial biofilms: from ecology to
molecular genetics. Microbiol Molec Biol Rev 2000; 64:847–
867.
43. Mah T-FC, O’Toole GA. Mechanisms of biofilm resistance to
antimicrobial agents. Trends Microbiol 2001; 9:34–39.
44. Nuryastuti T, van der Mei HC, Busscher HJ, Iravati S, Aman AT,
Krom BP. Effect of cinnamon oil on icaA expression and biofilm
formation by Staphylococcus epidermidis.Appl Environ Micro-
biol 2009; 75:6850–6855.
45. Koraichi Saad I, Hassan L, Ghizlane Z, Hind M, Adnane R.
Carvacrol and thymol components inhibiting Pseudomonas
aeruginosa adherence and biofilm formation. Afr J Microbiol
Res 2011; 5:3229–3232.
46. Nostro A, Roccaro AS, Bisignano G, Marino A, Cannatelli MA,
Pizzimenti FC, et al.Effects of oregano, carvacrol and thymol
on Staphylococcus aureus and Staphylococcus epidermidis
biofilms. J Med Microbiol 2007; 56:519–523.
47. El Abed S, Houari A, Latrache H, Remmal A, Koraichi SI. In vitro
activity of four common essential oil components against
biofilm-producing Pseudomonas aeruginosa.Res J Microbiol
2011; 6:394.
48. Braga PC, Culici M, Alfieri M, Dal Sasso M. Thymol inhibits
Candida albicans biofilm formation and mature biofilm. Int J
Antimicrob Agents 2008; 31:472–477.
49. Tseng H-K, Perfect JR. Strategies to manage antifungal drug
resistance. Expert Opin Pharmacother 2011; 12:241–256.
50. Gonzales FP, Maisch T. Photodynamic inactivation for control-
ling Candida albicans infections. Fungal Biol 2012; 116:1–10.
51. Guo N, Liu J, Wu X, Bi X, Meng R, Wang X, et al.Antifungal
activity of thymol against clinical isolates of fluconazole-sen-
sitive and-resistant Candida albicans.J Med Microbiol 2009;
58:1074–1079.
52. Ahmad A, Khan A, Akhtar F, Yousuf S, Xess I, Khan L, et al.
Fungicidal activity of thymol and carvacrol by disrupting
ergosterol biosynthesis and membrane integrity against Can-
dida. Eur J Clin Microbiol Infect Dis 2011; 30:41–50.
53. Kordali S, Aslan I, C¸ almas¸ur O, Cakir A. Toxicity of essential oils
isolated from three Artemisia species and some of their major
components to granary weevil, Sitophilus granarius (L.) (Co-
leoptera: Curculionidae). Industrial Crops Products 2006;
23:162–170.
54. Kordali S, Cakir A, Ozer H, Cakmakci R, Kesdek M, Mete E.
Antifungal, phytotoxic and insecticidal properties of essential
oil isolated from Turkish Origanum acutidens and its three
components, carvacrol, thymol and p-cymene. Bioresource
Technol 2008; 99:8788–8795.
55. Poonpaiboonpipat T, Pangnakorn U, Suvunnamek U, Teerarak
M, Charoenying P, Laosinwattana C. Phytotoxic effects of
essential oil from Cymbopogon citratus and its physiological
mechanisms on barnyardgrass (Echinochloa crus-galli). Indus-
trial Crops Products 2013; 41:403–407.
56. Yanishlieva NV, Marinova EM, Gordon MH, Raneva VG. Anti-
oxidant activity and mechanism of action of thymol and
carvacrol in two lipid systems. Food Chem 1999; 64:59–66.
57. Vasconcelos LCd, Sampaio FC, Albuquerque AdJdR, Vascon-
celos LCdS. Cell viability of Candida albicans against
the antifungal activity of thymol. Braz Dent J 2014; 25:277–
281.
58. Bennis S, Chami F, Chami N, Bouchikhi T, Remmal A. Surface
alteration of Saccharomyces cerevisiae induced by thymol and
eugenol. Lett Appl Microbiol 2004; 38:454–458.
59. Martı´nez-Romero D, Guille
´n F, Valverde JM, Baile
´n G, Zapata
P, Serrano M, et al.Influence of carvacrol on survival of Botrytis
cinerea inoculated in table grapes. Int J Food Microbiol 2007;
115:144–148.
60. Navarro D, Dı´az-Mula HM, Guille
´n F, Zapata PJ, Castillo S,
Serrano M, et al.Reduction of nectarine decay caused by
Rhizopus stolonifer,Botrytis cinerea and Penicillium digitatum
with aloe vera gel alone or with the addition of thymol. Int J
Food Microbiol 2011; 151:241–246.
61. Tsao R, Zhou T. Antifungal activity of monoterpenoids against
postharvest pathogens Botrytis cinerea and Monilinia fructi-
cola.J Essential Oil Res 2000; 12:113–121.
62. Sikkema J, De Bont J, Poolman B. Mechanisms of membrane
toxicity of hydrocarbons. Microbiol Rev 1995; 59:201–222.
63. Tait SW, Green DR. Mitochondria and cell death: outer mem-
brane permeabilization and beyond. Nat Rev Molec Cell Biol
2010; 11:621–632.
64. Vigan M. Essential oils: renewal of interest and toxicity. Eur J
Dermatol 2010; 20:685–692.
65. Kohlert C, Schindler G, Ma
¨rz RW, Abel G, Brinkhaus B,
Derendorf H, et al.Systemic availability and pharmacokinetics
of thymol in humans. J Clin Pharmacol 2002; 42:731–737.
68 Reviews in Medical Microbiology 2017, Vol 28 No 2
... Besides films and coatings, the application of several plant-based compounds as additives in food products has been increasingly regarded as a safe alternative to the conventional synthetic compounds used to preserve food products and extend their shelf life [71]. Due to their antimicrobial activity and functional properties, various essential oils and compounds such as limonene, thymol, oleuropein, and carvacrol have been the focus of several studies [54,72,73]. ...
... Ozogul et al. [74] reported that the antibacterial activity of thyme essential oil was remarkably efficient against foodborne pathogenic bacteria and fish spoilage bacteria; its minimal inhibitory concentration was lower than that observed for tetracycline, streptomycin, and neomycin. Memar et al. [71] detected identical antibacterial and antifungal activity in carvacrol. This may result from the similarity of conformation and origin of these compounds since both are extracted from the Lamiaceae family of plants [75]. ...
... This may result from the similarity of conformation and origin of these compounds since both are extracted from the Lamiaceae family of plants [75]. Antimicrobial, antioxidant, anti-inflammatory, cardioprotective, and neuroprotective properties have been reported for carvacrol [71]. Limonene has also been commonly used in the food industry due to its aromatic and flavor-inducing properties [11]. ...
Article
Seafood is essential to a healthy and varied diet due to its highly nutritious characteristics. However, seafood products are highly perishable, which results in financial losses and quality concerns for consumers and the industry. Due to changes in consumer concerns, demand for healthy products has increased. New trends focusing on reducing synthetic preservatives require innovation and the application of additional or alternative strategies to extend the shelf life of this type of product. Currently, refrigeration and freezing storage are the most common methods for fish preservation. However, refrigeration alone cannot provide long shelf-life periods for fish, and freezing worsens sensorial characteristics and consumer interest. Therefore, the need to preserve seafood for long periods without exposing it to freezing temperatures exists. This review focuses on the application of other approaches to seafood products, such as biodegradable films and coating technology; superchilling; irradiation; high-pressure processing; hyperbaric storage; and biopreservation with lactic acid bacteria, bacteriocins, or bacteriophages. The efficiency of these techniques is discussed based on their impact on microbiological quality, sensorial degradation, and overall preservation of the product's nutritional properties. Although these techniques are already known, their use in the industrial processing of seafood is not widespread. Thus, the novelty of this review is the aggregation of recent studies on shelf life extension approaches, which provide useful information for the selection of the most appropriate technology and procedures and industrial innovation. Despite the fact that all techniques inhibit or delay bacterial proliferation and product decay, an undesirable sensory impact may occur depending on the treatment conditions. Although no technique appears to replace refrigeration, the implementation of additional treatments in the seafood processing operation could reduce the need for freezing, extending the shelf life of fresh unfrozen products.
... [ [154][155][156][157][158][159][160][161][162][163] α-terpineol Essential oils of pine and petitgrain. ...
... Thymol is a monoterpene phenol with multiple biological activities. Studies on human neutrophils show that, besides antimicrobial [154][155][156] and antioxidant effects, thymol also provides anti-inflammatory activity [157]. Thymol's antioxidant effects are exerted by positively influencing docosahexaenoic acid (DHA) concentration in the brain [158]. ...
Article
Full-text available
Chronic inflammation is one of the hallmarks of chronic wounds and is tightly coupled to immune regulation. The dysregulation of the immune system leads to continuing inflammation and impaired wound healing and, subsequently, to chronic skin wounds. In this review, we discuss the role of the immune system, the involvement of inflammatory mediators and reactive oxygen species, the complication of bacterial infections in chronic wound healing, and the still-underexplored potential of natural bioactive compounds in wound treatment. We focus on natural compounds with antioxidant, anti-inflammatory, and antibacterial activities and their mechanisms of action, as well as on recent wound treatments and therapeutic advancements capitalizing on nanotechnology or new biomaterial platforms.
... This type of stress could eventually be responsible for many human disorders, such as cancer, atherosclerosis, ischemiaÀreperfusion damage, neurodegenerative injury and the aging process (Cho and Kleeberger 2007). In addition, antioxidants may also have antibacterial (Memar et al., 2017) and antifungal effects (Rahmouni et al., 2019) and they can be used as insecticides (Oulebsir et al. 2018). In particular, Phenolics can be used as an alternative antimicrobial agent against antibioticÀresistant pathogenic bacteria (Memar et al., 2017). ...
... In addition, antioxidants may also have antibacterial (Memar et al., 2017) and antifungal effects (Rahmouni et al., 2019) and they can be used as insecticides (Oulebsir et al. 2018). In particular, Phenolics can be used as an alternative antimicrobial agent against antibioticÀresistant pathogenic bacteria (Memar et al., 2017). It has been demonstrated that, whole faba bean seeds decrease insulin and cholesterol levels in hyper-cholesterolemic patients (Weck et al., 1983). ...
Article
The effects of dehulling and milling of seeds on the volatiles of two Vicia faba L. cultivars were evaluated using headspace-solid phase micro-extraction (HS-SPME) coupled to gas chromatography�mass spectrome�try (GC-MS). The phenolic constituents and antioxidants activities were also estimated on the same kind of samples. A total of 36 volatiles belonging to six different chemical classes were identified. Among them, 11 compounds were determined in the emission profile of whole faba bean seeds, 19 from dehulled legume seeds, 14 from whole seed flours, and 24 from dehulled seed flours. A difference in term of volatiles was observed between whole and dehulled seeds and flours. Additionally, the evaluation of phenolic compounds and antioxidant activities showed significant differences between dehulled seeds in comparison to the corre�sponding whole ones, in terms of total antioxidant capacity, DPPH radical scavenging activity, b-carotene bleaching test, and iron reducing power. Nevertheless, the dehulling effect did not affect the total phenols, flavonoids, and tannins contents. Besides phenolic compounds in whole and dehulled faba bean flours, ascor�bic acid was detected by HPLC-UV-DAD in both cultivars.
... Several studies have described that thymol and carvacrol are able to inhibit the growth of preformed biofilm and interfere with biofilm formation during planktonic growth. Memar et al., (49) reported that carvacrol and thymol attenuated biofilm formation in S. aureus and S. epidermidis on polystyrene microplates. Thymol can prevent the early stages of biofilm formation and interfere with the formation of mature biofilms due to metabolic activity in biofilms. ...
Article
Full-text available
Background: The altitudinal and geographical variability of the Aurès mountains of Algeria favored the existence of some endemic and rare varieties of medicinal plants. The aim of the present work is to determine the chemical composition, antimicrobial and antibiofilm properties of the essential oils (EOs) from aerial parts of four medicinal plants from Aurès region of Algeria; Juniperus thurifera L., Juniperus oxycedrus L., Salvia officinalis L. and Thymus ciliatus ssp. munbyanus (Boiss. & Reut.) Batt. on coagulase negative staphylococci (CoNS) isolates. Methodology: Extraction of EOs from the four plant materials was carried out by hydro-distillation, and the EO yield expressed in gram of the distillate per 100 grams of dry matter. The chemical composition of the EOs was analyzed by gas chromatography-mass spectrometry (GC-MS) method. In vitro antibacterial and antibiofilm activities of the EOs were evaluated against CoNS previously isolated at the Anti-Cancer Center of Batna, Algeria using the agar disc diffusion assay and biofilm inhibition study, respectively. Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) of the EOs of S. officinalis L. and T. ciliatus ssp. munbyanus were determined by the dilution method. Results: Twenty-seven and 41 compounds rich in monoterpene hydrocarbons were identified from J. oxycedrus and J. thurifera plants respectively, while 45 and 32 compounds, constituted mainly by oxygenated mono-terpenes, were identified from S. officinalis L. and T. ciliatus ssp. munbyanus, respectively. The EOs of T. ciliatus ssp. munbyanus showed the most inhibitory activity of all the four plants on CoNS isolates (n=66) with mean inhibition zone diameter of 24.99±6.29mm, and mean MIC and MBC values of 2.65±3.77mg/ml and 5.31±7.41mg/ml respectively, followed by S. officinalis L., with mean inhibition zone diameter of 13.38± 6.52mm, and mean MIC and MBC values of 27.53±28.2 mg/ml and 31.97±33.19 mg/ml respectively (p<0.0001 by one-way ANOVA). Also, percentage biofilm inhibition of CoNS isolates (n=59) was high for EOs of T. ciliatus ssp. munbyanus (65.63±10.71%) and S. officinalis L. (53.13±5.83%), although was significantly higher for T. ciliatus ssp. munbyanus compared to S. officinalis L. (p<0.0001, t=7.874). Conclusion: Essential oils from T. ciliatus ssp. munbyanus and S. officinalis L. could represent an alternative to classical antibiotics against planktonic cells and biofilms of CoNS.
... Ces deux composés liquides, insolubles dans l'eau et toxiques pour les cellules microbiennes, peuvent être utilisés pour obtenir des systèmes aqueux biphasiques dans lesquels les huiles phytochimiques sont utilisées comme solvants organiques du bromure de miconazoctylium (Figure 3.6). 344,345 Ces systèmes eau/huile en présence de β-CD peuvent être utilisés pour construire des plateformes d'administration de médicaments basées sur des émulsions de Pickering en utilisant le concept de tectonique colloïdale. Dans ces milieux, les interactions hôte-invité entre les tectons polaires et phytochimiques (CD et huile) conduisent à des particules structurées "amphiphiles" qui s'adsorbent à l'interface eau/huile, conduisant à des émulsions de Pickering. ...
Thesis
Les émulsions sont des systèmes micro-dispersés classiquement stabilisés par des molécules tensioactives. En raison de leur impact potentiellement négatif sur l’environnement, les tensioactifs tendent à être remplacés par des particules colloïdales conduisant ainsi aux émulsions de Pickering. Elles, bénéficient aujourd’hui d’un regain d’intérêt notamment dans le domaine de la catalyse. En effet, l’usage de particules répondant à certains stimuli comme le pH ou la température permet de contrôler le type d’émulsion voire sa déstabilisation, ce qui peut présenter un avantage indéniable en fin de réaction. L’objectif de ce travail était donc de développer de nouveaux systèmes d’émulsions de Pickering à base de particules réactives. Dans un premier temps, nous nous sommes intéressés à deux types de particules polymériques : la poly(4-vinylpyridine) (P4VP), sensible au pH et au sel, et la polyéthylèneimine (PEI), sensible au pH et à la température. Les émulsions ainsi obtenues en présence de différentes huiles ont été caractérisées et les effets du pH, de la température et de l’ajout de sel ont été étudiés démontrant la réversibilité des systèmes sous l’action de ces stimuli. Dans un second temps, des émulsions aux propriétés antibactériennes, antifongiques et antibiofilms ont été élaborées à partir de l’auto-assemblage de cyclodextrines et d’huile phytochimiques par le biais de complexes d’inclusion insolubles. Ces émulsions se sont révélées très efficaces dans la lutte contre les agents pathogènes. Finalement, la catalyse interfaciale de Pickering a été appliquée avec succès en vue de la synthèse des acides adipique et subérique en associant le phosphotungstate de tri(dodécyltriméthylammonium) [C12]3[PW12O40], de la silice greffée avec des groupements alkyles et sulfoniques, C18/C3SO3H@SiO2, et des sels de phosphate acides en tant que co-catalyseurs. Dans les conditions optimales, une conversion quantitative des oléfines associée à des rendements en acide boostés à 70 et 65 % en présence de Na2HPO4 et (C12)H2PO4, respectivement. Ces additifs potentialisent l’auto-assemblage des particules. L’existence de ces systèmes repose sur l’adaptabilité des particules aux environnements particuliers et montre que leurs propriétés physicochimiques peuvent être modulées afin de leur conférer les caractéristiques souhaitées.
... Studies on the mechanistic details of the antimicrobial activity of carvacrol are available [26,[41][42][43][44][45]; however, among these only Chueca et al. [44] and Pesingi et al. [45] have reported its relation to efflux pumps to a certain extent. Chueca et al. [44] have analyzed the transcriptional response of Escherichia coli MG1655 under carvacrol treatment and reported a relation with genes encoding AcrAB-TolC multidrug efflux system in aiding the cells to cope with carvacrol stress. ...
Article
Full-text available
The essential oil carvacrol from oregano displays a wide range of biological activities among which is found the inhibition of efflux pumps. Thus, using carvacrol, the current work undertook the effort to potentiate the antimicrobial activity of berberine, a natural product with limited antimicrobial efficacy due to its efflux. Following the selection of concentrations for the combinatorial treatments, guided by checkerboard microtiter plate assay and growth experiments, ethidium bromide accumulation assay was used to find that 25 μg mL⁻¹ carvacrol displayed a weak efflux pump inhibitor character in Bacillus subtilis. Scanning electron microscopy images and cellular material leakage assays showed that carvacrol at this concentration neither altered the morphology nor the permeability of the membrane alone but when combined with 75 μg mL⁻¹ berberine. Among the efflux pumps of different families found in B. subtilis, except for BmrA and Mdr, the increase in the expressional changes was striking, with Blt displaying ~ 4500-fold increase in expression under the combination treatment. Overall, the findings demonstrated that carvacrol potentiated the effect of berberine; however, not only multiple pumps but also different targets may be responsible for the observed activity.
... These results can be explained by the richness of the hydrosols of this thyme in thymol and carvacrol as we mentioned earlier. These two compounds are active molecules of Lamiaceae family and they possess an antimicrobial effect [36]. Besides, they have been reported to have the capacity to permeabilize and depolarize the bacterial membrane [37-38]. ...
Chapter
Much recent progress has been achieved in delivering medications to our bodies. Drug delivery system development has grown exponentially. Some medications have a hurdle of low bioavailability; to counter this, hydrogels have been used as a tool to delimit low bioavailability and side effects. Nanoparticle (NP) and hydrogel composite (NPH) nanoformulations play a significant role in the site-specific or targeted and regulated supply of medicinal products. The field of nanotechnology comprises intracells and particles of 100 nm in size along with devices. Nanoformulations can cross the bloodebrain barrier, improving safety, effectiveness, and patient conformity. These formulations have the following properties: drug loading capability, drug stability, drug release rates, and targeting capacity. Hydrogels are made of cross-connected polymers that can swell out when in contact with water or aqueous media.
Article
Full-text available
Enterococcus faecalis is a leading causative pathogen of recalcitrant infections affecting heart valves, urinary tract, surgical wounds and dental root canals. Its robust biofilm formation, production of virulence factors and antibiotic resistance contribute significantly to its pathogenicity in persistent infections. The decreased effectiveness of most of antibiotics in preventing and/or eradicating E. faecalis biofilms mandates the discovery of alternative novel antibiofilm agents. Phytochemicals are potential sources of antibiofilm agents due to their antivirulence activity, diversity of chemical structure and multiple mechanisms of action. In this review, we describe the phenotypic and genetic attributes that contribute to antimicrobial tolerance of E. faecalis biofilms. We illuminate the benefits of implementing the phytochemicals to tackle microbial pathogens. Finally, we report the antibiofilm activity of phytochemicals against E. faecalis, and explain their mechanisms of action. These compounds belong to different chemical classes such as terpenes, phenylpropenes, flavonoids, curcuminoids and alkaloids. They demonstrate the ability to inhibit the formation of and/or eradicate E. faecalis biofilms. However, the exact mechanisms of action of most of these compounds are not fully understood. Therefore, the future studies should elucidate the underlying mechanisms in detail.
Article
A novel antimicrobial chitosan-gelatin based edible coating fortified with thyme and papaya leaves extract was prepared for improving the quality and shelf-life of chicken fillets and Kareish cheese during chilled storage at 4 ± 1 °C. The samples were dipped for 10 min. in distilled water (control), chitosan-gelatin (CG), chitosan-gelatin +2% papaya leaves extract (CG + P) and chitosan-gelatin +2% thyme extract (CG + Th). The coated and uncoated samples were examined periodically for sensory attributes, pH, TBARs, total aerobic mesophilic (TAM), total Enterobacteriaceae (TE), and total yeasts and molds counts (TYM). Sensory evaluation revealed that chicken fillet and cheese samples coated with CG + P were the best in terms of tenderness, juiciness, body & texture and flavor. CG + Th exhibited the highest antimicrobial and antioxidant effect, followed by CG + P. The results of microbiological, physicochemical and sensory analysis of this study demonstrated that the application of CG + P or CG + Th could be a promising method for increasing the shelf life and improving the quality of chicken fillet and Kareish cheese.
Article
Full-text available
The Caenorhabditis elegans model can be used to study Candida albicans virulence and host immunity, as well as to identify plant-derived natural products to use against C. albicans. Thymol is a hydrophobic phenol compound from the aromatic plant thyme. In this study, the in vitro data demonstrated concentration-dependent thymol inhibition of both C. albicans growth and biofilm formation during different developmental phases. With the aid of the C. elegans system, we performed in vivo assays, and our results further showed the ability of thymol to increase C. elegans life span during infection, inhibit C. albicans colony formation in the C. elegans intestine, and increase the expression levels of host antimicrobial genes. Moreover, among the genes that encode the p38 MAPK signaling pathway, mutation of the pmk-1 or sek-1 gene decreased the beneficial effects of thymol's antifungal activity against C. albicans and thymol's maintenance of the innate immune response in nematodes. Western blot data showed the level of phosphorylation of pmk-1 was dramatically decreased against C. albicans. In nematodes, treatment with thymol recovered the dysregulation of pmk-1 and sek-1 gene expressions, the phosphorylation level of PMK-1 caused by C. albicans infection. Therefore, thymol may act, at least in part, through the function of the p38 MAPK signaling pathway to protect against C. albicans infection and maintain the host innate immune response to C. albicans. Our results indicate that the p38 MAPK signaling pathway plays a crucial role in regulating the beneficial effects observed after nematodes infected with C. albicans were treated with thymol.
Article
Full-text available
Pseudomonas aeruginosa has a high propensity to develop biofilms that are resistant to exogenous deleterious agents. The aim of this study was to investigate whether carvacrol and thymol can interfere with adherence phenomena as well as acting on biofilm formation. Tests of P. aeruginosa strains showed that carvacrol and thymol interferes with the starting phases of adherence as well as with P. aeruginosa biofilms. Carvacrol and thymol (2MIC) inhibition was 97±8.5 and 89±6.3% for P. aeruginosa (ATCC 27853) and 72±4.6 and 69±6.8% for P. aeruginosa (CIP A22) adherence respectively. Carvacrol (2MIC) inhibition exceeds 90% for P. aeruginosa (ATCC 27853) and P. aeruginosa (IL5) biofilm. Thymol (2MIC) inhibition is 86±2.1, 54±5.9 and 70±4.3% for P. aeruginosa (ATCC 27853) P. aeruginosa (CIP A22), P. aeruginosa (IL5), respectively.
Article
Full-text available
Pseudomonas aeruginosa has a high propensity to develop biofilms that are resistant to exogenous deleterious agents. The aim of this study was to investigate whether carvacrol and thymol can interfere with adherence phenomena as well as acting on biofilm formation. Tests of P. aeruginosa strains showed that carvacrol and thymol interferes with the starting phases of adherence as well as with P. aeruginosa biofilms. Carvacrol and thymol (2MIC) inhibition was 97 +/- 8.5 and 89 +/- 6.3% for P. aeruginosa (ATCC 27853) and 72 +/- 4.6 and 69 +/- 6.8% for P. aeruginosa (CIP A22) adherence respectively. Carvacrol (2MIC) inhibition exceeds 90% for P. aeruginosa (ATCC 27853) and P. aeruginosa (IL5) biofilm. Thymol (2MIC) inhibition is 86 +/- 2.1, 54 +/- 5.9 and 70 +/- 4.3% for P. aeruginosa (ATCC 27853) P. aeruginosa (CIP A22), P. aeruginosa (IL5), respectively.
Article
Full-text available
Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.
Article
Microbial transformations of cyclic hydrocarbons have received much attention during the past three decades. Interest in the degradation of environmental pollutants as well as in applications of microorganisms in the catalysis of chemical reactions has stimulated research in this area. The metabolic pathways of various aromatics, cycloalkanes, and terpenes in different microorganisms have been elucidated, and the genetics of several of these routes have been clarified. The toxicity of these compounds to microorganisms is very important in the microbial degradation of hydrocarbons, but not many researchers have studied the mechanism of this toxic action. In this review, we present general ideas derived from the various reports mentioning toxic effects. Most importantly, lipophilic hydrocarbons accumulate in the membrane lipid bilayer, affecting the structural and functional properties of these membranes. As a result of accumulated hydrocarbon molecules, the membrane loses its integrity, and an increase in permeability to protons and ions has been observed in several instances. Consequently, dissipation of the proton motive force and impairment of intracellular pH homeostasis occur. In addition to the effects of lipophilic compounds on the lipid part of the membrane, proteins embedded in the membrane are affected. The effects on the membrane-embedded proteins probably result to a large extent from changes in the lipid environment; however, direct effects of lipophilic compounds on membrane proteins have also been observed. Finally, the effectiveness of changes in membrane lipid composition, modification of outer membrane lipopolysaccharide, altered cell wall constituents, and active excretion systems in reducing the membrane concentrations of lipophilic compounds is discussed. Also, the adaptations (e.g., increase in lipid ordering, change in lipid/protein ratio) that compensate for the changes in membrane structure are treated.
Article
Microbial transformations of cyclic hydrocarbons have received much attention during the past three decades. Interest in the degradation of environmental pollutants as well as in applications of microorganisms in the catalysis of chemical reactions has stimulated research in this area. The metabolic pathways of various aromatics, cycloalkanes, and terpenes in different microorganisms have been elucidated, and the genetics of several of these routes have been clarified. The toxicity of these compounds to microorganisms is very important in the microbial degradation of hydrocarbons, but not many researchers have studied the mechanism of this toxic action. In this review, we present general ideas derived from the various reports mentioning toxic effects. Most importantly, lipophilic hydrocarbons accumulate in the membrane lipid bilayer, affecting the structural and functional properties of these membranes. As a result of accumulated hydrocarbon molecules, the membrane loses its integrity, and an increase in permeability to protons and ions has been observed in several instances. Consequently, dissipation of the proton motive force and impairment of intracellular pH homeostasis occur. In addition to the effects of lipophilic compounds on the lipid part of the membrane, proteins embedded in the membrane are affected. The effects on the membrane-embedded proteins probably result to a large extent from changes in the lipid environment; however, direct effects of lipophilic compounds on membrane proteins have also been observed. Finally, the effectiveness of changes in membrane lipid composition, modification of outer membrane lipopolysaccharide, altered cell wall constituents, and active excretion systems in reducing the membrane concentrations of lipophilic compounds is discussed. Also, the adaptations (e.g., increase in lipid ordering, change in lipid/protein ratio) that compensate for the changes in membrane structure are treated.
Article
The aim of the current research work was to study the chemical composition of the essential oil of Monarda punctata along with evaluating the essential oil and its major components for their antibacterial effects against some frequently encountered respiratory infection causing pathogens. Gas chromatographic mass spectrometric analysis revealed the presence of 13 chemical constituents with thymol (75.2%), p-cymene (6.7%), limonene (5.4), and carvacrol (3.5%) as the major constituents. The oil composition was dominated by the oxygenated monoterpenes. Antibacterial activity of the essential oil and its major constituents (thymol, p-cymene, limonene) was evaluated against Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Haemophilus influenzae and Escherichia coli. The study revealed that the essential oil and its constituents exhibited a broad spectrum and variable degree of antibacterial activity against different strains. Among the tested strains, Streptococcus pyogenes, Escherichia coli and Streptococcus pneumoniae were the most susceptible bacterial strain showing lowest MIC and MBC values. Methicillin-resistant Staphylococcus aureus was the most resistant bacterial strain to the essential oil treatment showing relatively higher MIC and MBC values. Scanning electron microscopy revealed that the essential oil induced potent and dose-dependent membrane damage in S. pyogenes and MRSA bacterial strains. The reactive oxygen species generated by the Monarda punctata essential oil were identified using 2', 7'-dichlorofluorescein diacetate (DCFDA).This study indicated that the Monarda punctata essential oil to a great extent and thymol to a lower extent triggered a substantial increase in the ROS levels in S. pyogenes bacterial cultures which ultimately cause membrane damage as revealed by SEM results.