Abstract
Multidrug resistant bacteria are a global threat for human and animal health. However, they are only part of the problem of antibiotic failure. Another bacterial strategy that contributes to their capacity to withstand antimicrobials is the formation of biofilms. Biofilms are associations of microorganisms embedded a self-produced extracellular matrix. They create particular environments that confer bacterial tolerance and resistance to antibiotics by different mechanisms that depend upon factors such as biofilm composition, architecture, the stage of biofilm development, and growth conditions. The biofilm structure hinders the penetration of antibiotics and may prevent the accumulation of bactericidal concentrations throughout the entire biofilm. In addition, gradients of dispersion of nutrients and oxygen within the biofilm generate different metabolic states of individual cells and favor the development of antibiotic tolerance and bacterial persistence. Furthermore, antimicrobial resistance may develop within biofilms through a variety of mechanisms. The expression of efflux pumps may be induced in various parts of the biofilm and the mutation frequency is induced, while the presence of extracellular DNA and the close contact between cells favor horizontal gene transfer. A deep understanding of the mechanisms by which biofilms cause tolerance/resistance to antibiotics helps to develop novel strategies to fight these infections.
Highlights
During the last few decades, a significant increase in the number of clinical and environmental multidrug-resistant (MDR) bacteria, called superbugs, has been reported. problematic in this respect are the major human pathogens, e.g., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp
The proportion of people infected with MDR bacteria varies among countries, with higher levels of resistance to those drugs more widely utilized for treating infections [2], and many pathogens have developed mechanisms to survive to practically all of the antibiotic families available on the market, for example K. pneumoniae
About 80% of the chronic and recurrent microbial infections in humans are caused by biofilms, some of which result in high mortality and morbidity rates [11,12], those caused by MDR bacteria
Summary
During the last few decades, a significant increase in the number of clinical and environmental multidrug-resistant (MDR) bacteria, called superbugs, has been reported Problematic in this respect are the major human pathogens, e.g., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. The proportion of people infected with MDR bacteria varies among countries, with higher levels of resistance to those drugs more widely utilized for treating infections (e.g., ciprofloxacin) [2], and many pathogens have developed mechanisms to survive to practically all of the antibiotic families available on the market, for example K. pneumoniae. Patients with cystic fibrosis or with assisted ventilation are susceptible to chronic infections by biofilm-forming P. aeruginosa [13] and A. baumannii [14], respectively These bacteria are well-known for acquiring MDR, and the resulting biofilms are almost impossible to treat [15]. We will describe the mechanisms responsible for recalcitrance and the currently proposed solutions to treat or prevent biofilm infections
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