Mechanisms of antimicrobial resistance in biofilms

Abstract

Most bacteria in nature exist in aggregated communities known as biofilms, and cells within a biofilm demonstrate major physiological changes compared to their planktonic counterparts. Biofilms are associated with many different types of infections which can have severe impacts on patients. Infections involving a biofilm component are often chronic and highly recalcitrant to antibiotic therapy as a result of intrinsic physical factors including extracellular matrix production, low growth rates, altered antibiotic target production and efficient exchange of resistance genes. This review describes the biofilm lifecycle, phenotypic characteristics of a biofilm, and contribution of matrix and persister cells to biofilms intrinsic tolerance to antimicrobials. We also describe how biofilms can evolve antibiotic resistance and transfer resistance genes within biofilms. Multispecies biofilms and the impacts of various interactions, including cooperation and competition, between species on tolerance to antimicrobials in polymicrobial biofilm communities are also discussed.

Keywords: Antimicrobial resistance; Bacteriology.

Fig. 1. The lifecycle of a surface attached biofilm.

Biofilm formation starts with the initial attachment of cells to a substrate (a), followed by irreversible attachment of cells (b), micro-colony formation (c) and biofilm maturation (d), and dispersal of cells or aggregates that move on to colonise other substrates (e).

Fig. 2. Components of the matrix that can hinder the absorption of antibiotics into the biofilm.

Positively charged antibiotics (such as aminoglycosides) can bind to negatively charged eDNA found in the matrix, reducing antibiotic penetration, polysaccharides can present a permeability barrier and secreted enzymes can break down antibiotics resulting in a reduced concentration of antibiotics reaching the bacteria cells^,.

Fig. 3. The three main mechanisms of HGT.

Transformation, the taking up of DNA from the environment into the bacterial cell, transduction, the insertion of DNA (red) into the bacteria by bacteriophage, and conjugation, the transfer of genes on a plasmid (white) from a donor to a recipient cell through direct contact via pili^,. The bacterial chromosome is shown in pink or black and the plasmid is shown in green.

Fig. 4. Heterogeneity of susceptibility of cells within a biofilm to antibiotics.

The repopulation of a biofilm infection by persisters (red) after actively growing biofilm cells are killed by stress such as antibiotics.