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Science against microbial pathogens: photodynamic therapy approaches.
Abstract and Figures
There is an emerging area of research to identify the application of photodynamic therapy (PDT) as a means to kill microbial pathogens. In fact, the first recorded observation in more than 100 years ago of photodynamic processes was inactivation of microorganism. In this volume of the Formatex Microbiology book titled: Science against microbial pathogens: communicating current research and technological advances, this chapter will focus on the use of
photosensitizer and light as anti-microbial agent against various microbes in different settings. The mechanism of action of PDT inactivating microorganisms, anti-microbial photosensitizing agents and light sources used for eliminating microorganisms will be covered. The success and challenges of using PDT to eradicate bacteria including antibiotic resistant bacteria will be discussed.
Free full-text is available at http://www.formatex.info/microbiology3/book/668-674.pdf
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... That membrane forms a protective barrier for the cells [25] thus the structure of the cell wall plays an important role in susceptibility to singlet oxygen [24]. Due to the negative charge of the cell membrane in G (-) bacteria, PS with positive charge are preferred for effective antimicrobial activity [26]. ...
Abstract
In times of multidrug resistance of bacteria, photodynamic therapy (PDT) seems to be promising in many fields of medicine, including endodontics, especially in the case of previous failures of root canal treatment and periapical lesions formation. PDT is based on the use of a light source and photosensitizers (PSs). Irradiation caused by the appropriately selected wavelength of light initiates the formation of singlet oxygen and/or free radicals, which provides the antimicrobial activity responsible for effective disinfection. In this manuscript, we compare the findings from all available papers of authors who perform their research in vivo. Despite the fact that they conducted their research in various ways, the results obtained in the course of these studies indicated an effective antibacterial effect of PDT in endodontic treatment. The second part of our work focuses on the perspectives of finding the best PSs that are used in PDT method with great expectations for materials based on graphene oxide as those which are not only carriers but also factors influencing the increase in the efficiency of the particles attached to them.
... In contrast, Gram-negative bacteria are less susceptible to this treatment, due to their more conjugate cell wall structure and additional negatively charged outer membrane. They require a higher concentration of PS and light dose [91]. It is better to use cationic PSs or supplementation of API with permeabilizing agents to achieve a significant cell death of Gram-negative bacteria [90]. ...
A spacecraft is a confined system that is inhabited by a changing microbial consortium, mostly originating from life-supporting devices, equipment collected in pre-flight conditions, and crewmembers. Continuous monitoring of the spacecraft's bioburden employing culture-based and molecular methods has shown the prevalence of various taxa, with human skin-associated microorganisms making a substantial contribution to the spacecraft microbiome. Microorganisms in spacecraft can prosper not only in planktonic growth mode but can also form more resilient biofilms that pose a higher risk to crewmembers' health and the material integrity of the spacecraft's equipment. Moreover, bacterial biofilms in space conditions are characterized by faster formation and acquisition of resistance to chemical and physical effects than under the same conditions on Earth, making most decontamination methods unsafe. There is currently no reported method available to combat biofilm formation in space effectively and safely. However, antibacterial photodynamic inactivation based on natural photosensitizers, which is reviewed in this work, seems to be a promising method.
Photodynamic therapy (PDT) is a clinically approved method of tumor treatment. Its unique mechanism of action results from minimal invasiveness and high selectivity towards transformed cells. However, visible light used to excite most photosensitizers has rather limited ability to penetrate tissues resulting in insufficient destruction of deeply seated malignant cells. Therefore, novel strategies for further potentiation of the anticancer effectiveness of PDT have been developed. These include combined treatments with surgery, chemo-and radiotherapy, strategies targeting cytoprotective mechanisms induced in PDT-treated cells, as well as attempts aimed at enhancement of PDT-mediated antitumor immune response. Moreover, new photosensitizers and novel light sources are being developed. Impressive progress in nanotechnology and understanding of tumor cell biology rise hopes for further improvements in this elegant and promising method of cancer treatment.
The health-promoting properties of sunlight have long been recognized, and there is evidence that a form of photochemotherapy was practised in some ancient civilizations. Modern phototherapy, however, commenced with the report by Finsen in 1901 that sunlight could be used to treat lupus vulgaris; in the wake of this discovery came the phototherapy of rickets, certain dermatological conditions, neonatal hyperbilirubinaemia and, most recently, cancer. In the latter case, the treatment requires, in addition to visible light, a photosensitizer and oxygen (photodynamic therapy, PDT): it is now widely held that singlet oxygen is the prime toxic agent in bringing about the death of cancer cells in PDT. The first generation of photosensitizers was characterized by haematoporphyrin, haematoporphyrin derivative (HpD), and various commercial extensions of HpD, particularly Photofrin. From 1980 onwards, the second generation photosensitimers began to appear, their development being in response to various disadvantages of HpD; the new sensitizers include porphyrins (and various isomers and analogues of porphyrins), chlorins, bacteriochlorins, and phthalocyanines. Future developments in PDT will certainly include the discovery of new photosensitizers and a broadening of the applications of the treatment by various means. For example, it may be possible to target tumour cells by attaching a photosensitizer to a monoclonal antibody; the development of a photosensitizer with a photobleaching propensity could help to reduce generalized photosensitization; and different photosensitizers may be designed for specific diagnostic or therapeutic functions. It is concluded that PDT is likely to play an increasingly important role in clinical medicine.
Abstract— The photodynamic inactivation by illuminated Rose Bengal of a number of bacterial species was compared. The gram-positive species, Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis and Streptococcus salivarius, were inactivated about 200x more quickly (99% inactivation) than a Salmonella typhimurium wildtype strain. The Salmonella inactivation curve exhibited an initial lag time during which bacteria were not significantly inactivated. The lag time for inactivation of a derivative of the wildtype Salmonella strain that is deficient in a large portion of its cell wall lipopolysaccharide coat was approximately half of the lag time for the wildtype strain but the subsequent rate of inactivation was approximately the same for the two strains. Dark preincubation of both Salmonella strains with Rose Bengal before illumination shortened the lag time, but did not increase the final rate of inactivation. Dark preincubation prior to illumination did not measurably change the inactivation curve of the gram-positive species. The lag time observed in the inactivation curves for Salmonella bacteria may reflect the time required for penetration of the Rose Bengal anion through the outer portion of the gram-negative cell wall to a critical location within the cell for effective photosensitization.
Abstract— The binding of hematoporphyrin derivated (Hpd) to lipid vesicles and bacterial membranes was determined by fluorescence spectroscopy. The fluorescence measurements of Hpd in aqueous solutions showed two bands at 613 and 677 nm. In lipid environments of lecithin vesicles the fluorescence spectrum was shifted to 631 and 692 nm, respectively. Hpd was rapidly bound to the cell membrane of Staphylococcus aureus while much less binding occurred in the presence of Escherichia coli. At the same time, spheroplasts of both bacteria were shown to bind Hpd to a similar extent. These results are well correlated with the photoinactivation of the gram positive bacteria with Hpd while the gram negative cells were shown to be resistant. The pH dependence of both Hpd binding to S. aureus as well as the photodynamic inhibitory effect of the same bacteria are similar. It is concluded that the segregation of Hpd to the cell membrane is a prerequisite for its photodynamic effect.
The photodynamic effects of deuteroporphyrin (DP), hematoporphyrin derivative (HPD), hematoporphyrin (HP), or protoporphyrin (PP) on a variety of anaerobic microorganisms were examined in this study. The majority of the species, among the 350 strains tested, were inhibited by concentrations of 2.5 g/ml of light-activated DP. Species found to be resistant to this treatment includedBilophila wadsworthia, Fusobacterium mortiferum, Fusobacterium varium, andBacteroides gracilis. These species were inhibited by concentrations of >60 g/ml of DP. The porphyrin-producing species,Porphyromonas andPrevotella spp, were all inhibited by 2.5 g/ml DP and light. Comparing the photodynamic activity of the porphyrins used onPorphyromonas strains resulted in the following pattern: DP>HPD>HP>PP.Porphyromonas spp., Gram-positive cocci, and many Gram-positive rods (excluding clostridia) were inactivated by hemin (a metal-containing porphyrin) at 10–20 g/ml. Hemin inhibitory action was not affected by light. Binding and insertion of DP into bacteria (both inactivated and non-inactivated strains by DP and light) were monitored by the characteristic fluorescence band of bound DP at 622 nm.Porphyromonas spp. bound DP tightly, whereas only low binding was seen withB. wadsworthia and other DP-resistant species. High binding of DP toB. wadsworthia can be achieved by pretreatment of the bacteria with imipenem or cefoxitin, -lactam agents known to interfere with the integrity of the cell wall. If cell wall integrity is disturbed (e.g., by these agents), inactivation ofB. wadsworthia by DP can occur.