Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance

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.

Antimicrobial Activity of Non-steroidal Anti-inflammatory Drugs on Biofilm: Current Evidence and Potential for Drug Repurposing

“…Biofilm formation is a common mechanism that promotes the survival and persistence of medically important bacteria in different abiotic and biotic niches. Approximately 80% of chronic and recurrent bacterial infections in humans are related to biofilms, some of which associated with high mortality and morbidity ( Banerjee et al, 2020 ; Uruén et al, 2020 ). Biofilms are defined as a community of sessile microbes held together by a secreted matrix of polysaccharides, proteins, and extracellular DNA, adherent to a surface, interface, or other cells.…”

An Antisense yycF RNA Modulates Biofilm Organization of Methicillin-Resistant Staphylococcus aureus and Pathogenicity in a Rat Model of Osteomyelitis

“…In our results, the growth rates, biofilm formation, and bacterial viability were significantly inhibited by overexpressing antisense yycF in the ASyycF ATCC29213 and ASyycF MRSA strains (Figures 2 and 3A,B). Biofilms are constructed with microorganisms embedded in a self-produced extracellular matrix [21]. As shown in the SEM observations, biofilm accumulation was obviously decreased in antisense yycF-overexpressing strains, which indicated that antisense yycF could negatively regulate biofilm metabolism (Figure 2C).…”

“…As shown in the SEM observations, biofilm accumulation was obviously decreased in antisense yycF-overexpressing strains, which indicated that antisense yycF could negatively regulate biofilm metabolism (Figure 2C). Indeed, biofilms are usually supposed to decrease the sensitivity of biofilm cells to various antimicrobial agents up to 1000-fold when compared with their planktonic forms [10,21,22]. Vancomycin, as the "gold standard" of treatment, has been applied clinically for serious MRSA infections [23].…”

“…As a major pathogen for most chronic and recurrent microbial infections in humans, S. aureus biofilms are involved in a wide range of infections. Some S. aureus infections are caused by multidrug-resistant bacteria and even cause high mortality and morbidity rates [21,25]. In addition to antibiotic resistance, biofilms can evade host immune clearance mechanisms and adhere to medical devices such as orthopedic prostheses [24,26].…”

Carboxy-Terminal Processing Protease Controls Production of Outer Membrane Vesicles and Biofilm in Acinetobacter baumannii

“…The P. aeruginosa ctpA mutant was also reported to attach robustly to glass surfaces [ 10 ]. eDNA, which is an essential constituent of biofilms, is secreted through active secretion or cell lysis [ 29 ]. Autolysis-dependent eDNA release has been shown to promote biofilm formation in several bacterial species [ 30 , 31 , 32 ].…”