Article

The role of bacterial biofilms in chronic infections

Københavns Universitet, København N, Denmark.
APMIS. Supplementum 05/2013; 121(136):1-58. DOI: 10.1111/apm.12099
Source: PubMed

ABSTRACT Acute infections caused by pathogenic bacteria have been studied extensively for well over 100 years. These infections killed millions of people in previous centuries, but they have been combated effectively by the development of modern vaccines, antibiotics and infection control measures. Most research into bacterial pathogenesis has focused on acute infections, but these diseases have now been supplemented by a new category of chronic infections caused by bacteria growing in slime-enclosed aggregates known as biofilms. Biofilm infections, such as pneumonia in cystic fibrosis patients, chronic wounds, chronic otitis media and implant- and catheter-associated infections, affect millions of people in the developed world each year and many deaths occur as a consequence. In general, bacteria have two life forms during growth and proliferation. In one form, the bacteria exist as single, independent cells (planktonic) whereas in the other form, bacteria are organized into sessile aggregates. The latter form is commonly referred to as the biofilm growth phenotype. Acute infections are assumed to involve planktonic bacteria, which are generally treatable with antibiotics, although successful treatment depends on accurate and fast diagnosis. However, in cases where the bacteria succeed in forming a biofilm within the human host, the infection often turns out to be untreatable and will develop into a chronic state. The important hallmarks of chronic biofilm-based infections are extreme resistance to antibiotics and many other conventional antimicrobial agents, and an extreme capacity for evading the host defences. In this thesis, I will assemble the current knowledge on biofilms with an emphasis on chronic infections, guidelines for diagnosis and treatment of these infections, before relating this to my previous research into the area of biofilms. I will present evidence to support a view that the biofilm lifestyle dominates chronic bacterial infections, where bacterial aggregation is the default mode, and that subsequent biofilm development progresses by adaptation to nutritional and environmental conditions. I will make a series of correlations to highlight the most important aspects of biofilms from my perspective, and to determine what can be deduced from the past decades of biofilm research. I will try to bridge in vitro and in vivo research and propose methods for studying biofilms based on this knowledge. I will compare how bacterial biofilms exist in stable ecological habitats and opportunistically in unstable ecological habitats, such as infections. Bacteria have a similar lifestyle (the biofilm) in both habitats, but the fight for survival and supremacy is different. On the basis of this comparison, I will hypothesize how chronic biofilm infections are initiated and how bacteria live together in these infections. Finally, I will discuss different aspects of biofilm infection diagnosis. Hopefully, this survey of current knowledge and my proposed guidelines will provide the basis and inspiration for more research, improved diagnostics, and treatments for well-known biofilm infections and any that may be identified in the future.

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    • "Many chronic infections are associated with the biofilm formation capability of the pathogenic bacteria (Von Rosenvinge et al., 2013). Examples of biofilm-associated infections include Pseudomonas aeruginosa (Mulcahy et al., 2013) and M. tuberculosis (Bjarnsholt, 2013). The capability to form biofilm is demonstrated to be the main strategy that the pathogenic bacteria like Pseudomonas use to survive against the host immune defense (Rybtke et al., 2011). "
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    • "Among opportunistic pathogenic bacteria, P. aeruginosa , which produces several virulence factors, is known to be an important human and plant pathogen, responsible for various infections, particularly in immunocompromised persons [10]. Besides this, the remarkable ability of P. aeruginosa to form biofilms in many environments renders antibiotic treatments inefficient and therefore promotes chronic infectious diseases [5] [11]. Three global nonmicrobicidal strategies have been proposed to struggle against pathogenic bacteria with biofilm formation ability by (i) avoiding microbial attachment to a surface; (ii) disrupting biofilm development and/or affecting biofilm architecture in order to enhance the penetration of antimicrobials; and (iii) affecting biofilm maturation and/or inducing its dispersion and degradation [8] [12] [13]. "
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    ABSTRACT: P. aeruginosa is an opportunistic pathogenic bacterium responsible for both acute and chronic infections. Beyond its natural resistance to many drugs, its ability to form biofilm, a complex biological system, renders ineffective the clearance by immune defense systems and antibiotherapy. The objective of this report is to provide an overview (i) on P. aeruginosa biofilm lifestyle cycle, (ii) on the main key actors relevant in the regulation of biofilm formation by P. aeruginosa including QS systems, GacS/GacA and RetS/LadS two-component systems and C-di-GMP-dependent polysaccharides biosynthesis, and (iii) finally on reported natural and synthetic products that interfere with control mechanisms of biofilm formation by P. aeruginosa without affecting directly bacterial viability. Concluding remarks focus on perspectives to consider biofilm lifestyle as a target for eradication of resistant infections caused by P. aeruginosa.
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    ABSTRACT: 1. Wstęp Problem zakażeń okołowszczepowych, zwanych rów nież zakażeniami związanymi z biomateriałem (BAIs – Biomaterial Associated Infections) nie został do końca poznany. Tytan, współcześnie stosowany w implantowanych wyrobach medycznych, w porówna-niu z innymi materiałami takimi jak lateks, poli(chlorek winylu) (PVC), teflon czy stal nierdzewna, wykazuje najmniejszą podatność na adhezję bakterii [21, 24, 99]. Ponadto unikatowa cecha tego pierwiastka sprawia, że materiały tytanowe mogą uzyskać funkcjonalne połą-czenie z żywą tkanką kostną w procesie zwanym osteo-integracją [16, 32]. Jednym z czynników, które mogą zakłócić ten proces jest kolonizacja powierzchni przez bakterie inicjujące rozwój zakażenia [42, 57]. Powsta-nie stanu zapalnego zapoczątkowuje proces resorpcji tkanki kostnej wokół wszczepu. Tym samym zaburzona zostaje stabilizacja wszczepu prowadząc do jego oblu-zowania na skutek mikro-ruchów. Postępująca rucho-mość implantu upośledza prawidłowe przenoszenie sił mechanicznych, co w konsekwencji prowadzi do jego utraty [11, 12]. Zakażenia okołowszczepowe mogą być przyczyną nieprawidłowego zrostu lub braku zrostu odłamów kostnych, zapalenia skóry lub błon śluzowych, zakażeń systemowych, wydłużenia czasu hospitalizacji i obniżenia jakości życia pacjenta [103]. Dodatkowo, zakażenia te niosą ryzyko groźnych dla życia powikłań na skutek bakteriemii u pacjentów poddanych leczeniu immunosupresyjnemu bądź z wszczepionymi sztucz-nymi zastawkami serca [37, 60]. Zakażenia okołowszczepowe są inicjowane przez drobnoustroje, które przyłączając się do powierzchni implantu żyją w postaci biofilmu [56]. Procedury lecznicze obejmujące chirurgiczne oczyszczenie po-wierzchni implantu oraz antybiotykoterapię (miejs-cową bądź ogólnoustrojową) nie zawsze są skuteczne [107, 110]. Przyczyną tego zjawiska jest fakt, że bakterie żyjące w biofilmie wykazują prawie 1000-krotnie wyż-szą oporność na większość środków bakteriobójczych niż formy planktonowe tych samych szczepów bak terii [29, 80]. Dodatkową przyczyną małej skuteczności antybiotykoterapii jest fakt, że penetracja leku do tka-nek zmienionych zapalnie, niedotlenionych, niekiedy martwiczych, jest znacznie obniżona [27]. Bakterie odpowiedzialne za większość zakażeń okołowszczepo-wych należą do gatunków oportunistycznych, co ma bezpośredni związek z faktem, że tkanki w okolicy oko-łowszczepowej charakteryzują się obniżoną odpornoś-cią na zakażenie. Strefa ta nazywana jest locus minoris Abstract: Bacterial infections accompanying implanted medical devices create serious clinical problems. Using titanium implants may reduce the rate of there infections. Physicochemical properties of titanium allow using it as implantable biomaterial to maintain osseointegration, phenomenon described as " biological and functional connection of the implant with the living bone ". One of the most important factors which can affect osseointegration is bacterial colonization of the implant surface and development of Biomaterial Associated Infection (BAI). Impaired osseointegration can increase the risk of subsequent loosening due to micromotion. BAI's in orthopaedics and maxillofacial surgery are serious complications, which ultimately lead to osteomyelitis with consequent devastating effects on bone and surrounding soft tissues. Implant associated infections are caused by microorganisms which adhere to the implant surface and then live clustered together in a highly hydrated extracellular matrix attached to the surface, known as bacterial biofilm. Simple debridement procedures with retention of prosthesis and chemotherapy with antimicrobial agents are the treatments not always effective against infections already established.
    Postepy Mikrobiologii 01/2014; 53(2):123-134. · 0.27 Impact Factor
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