ReviewAntibiotic resistance of bacteria in biofilms
Section snippets
Resistance mechanisms
The familiar mechanisms of antibiotic resistance, such as efflux pumps, modifying enzymes, and target mutations,12 do not seem to be responsible for the protection of bacteria in a biofilm. Even sensitive bacteria that do not have a known genetic basis for resistance can have profoundly reduced susceptibility when they form a biofilm. For example, a β-lactamase-negative strain of Klebsiella pneumoniae had a minimum inhibitory concentration of 2 μg/mL ampicillin in aqueous suspension.13 The same
Multicellular nature of biofilm defence
All three main hypotheses of biofilm resistance to antibiotics depend on the multicellular nature of biofilms.37 An antimicrobial agent cannot slowly or incompletely penetrate the biofilm unless the micro-organisms form aggregates that affect its diffusion. Local variations in the concentrations of microbial substrates and products develop only when a cluster of cells reaches a critical size and the bacteria exert their combined metabolic activity. The small population of cells that
Potential for new therapies
More work is needed to fully elucidate antibiotic resistance mechanisms in biofilms and develop new therapeutic strategies, but we have enough evidence to make some observations and suggestions. Clearly, there are multiple resistance mechanisms that can act together. Antibiofilm therapies might have to thwart more than one mechanism simultaneously to be clinically effective. Heterogeneity is a common theme of these resistance mechanisms; micro-organisms in a biofilm exist in a broad spectrum of
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