Elsevier

The Lancet

Volume 358, Issue 9276, 14 July 2001, Pages 135-138
The Lancet

Review
Antibiotic resistance of bacteria in biofilms

https://doi.org/10.1016/S0140-6736(01)05321-1Get rights and content

Summary

Bacteria that adhere to implanted medical devices or damaged tissue can encase themselves in a hydrated matrix of polysaccharide and protein, and form a slimy layer known as a biofilm. Antibiotic resistance of bacteria in the biofilm mode of growth contributes to the chronicity of infections such as those associated with implanted medical devices. The mechanisms of resistance in biofilms are different from the now familiar plasmids, transposons, and mutations that confer innate resistance to individual bacterial cells. In biofilms, resistance seems to depend on multicellular strategies. We summarise the features of biofilm infections, review emerging mechanisms of resistance, and discuss potential therapies.

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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