Aminoglycoside antibiotics induce bacterial biofilm formation

Abstract

Biofilms are adherent aggregates of bacterial cells that form on biotic and abiotic surfaces, including human tissues. Biofilms resist antibiotic treatment and contribute to bacterial persistence in chronic infections. Hence, the elucidation of the mechanisms by which biofilms are formed may assist in the treatment of chronic infections, such as Pseudomonas aeruginosa in the airways of patients with cystic fibrosis. Here we show that subinhibitory concentrations of aminoglycoside antibiotics induce biofilm formation in P. aeruginosa and Escherichia coli. In P. aeruginosa, a gene, which we designated aminoglycoside response regulator (arr), was essential for this induction and contributed to biofilm-specific aminoglycoside resistance. The arr gene is predicted to encode an inner-membrane phosphodiesterase whose substrate is cyclic di-guanosine monophosphate (c-di-GMP)-a bacterial second messenger that regulates cell surface adhesiveness. We found that membranes from arr mutants had diminished c-di-GMP phosphodiesterase activity, and P. aeruginosa cells with a mutation changing a predicted catalytic residue of Arr were defective in their biofilm response to tobramycin. Furthermore, tobramycin-inducible biofilm formation was inhibited by exogenous GTP, which is known to inhibit c-di-GMP phosphodiesterase activity. Our results demonstrate that biofilm formation can be a specific, defensive reaction to the presence of antibiotics, and indicate that the molecular basis of this response includes alterations in the level of c-di-GMP.

Defining Genetic Fitness Determinants and Creating Genomic Resources for an Oral Pathogen

“…Biofilm formation is a common stress response in many bacteria (55), and we hypothesized that a similar response was occurring in A. actinomycetemcomitans when exposed to erythromycin. A few factors that mediate antibiotic-induced attachment have been characterized (56,57). However, to our knowledge such factors have not been explored systematically.…”

“…This clinically relevant behavior could prime A. actinomycetemcomitans for higher, more lethal antibiotic concentrations during infection. In other bacteria, similar phenomena are mediated by cyclic di-GMP signaling (56) and extracellular DNA release (57). To discover factors that mediate this process in A. actinomycetemcomitans, we developed a novel Tn-seq-based screen (Fig.…”

Bacterial adaptation to sublethal antibiotic gradients can change the ecological properties of multitrophic microbial communities

“…Gentamicin is an aminoglycoside bactericidal antibiotic that inhibits translation, meaning that it kills bacterial cells and therefore reduces bacterial abundance [26]. Gentamicin was chosen because it is widely used in clinical environments and because it affects bacterial evolution even at sublethal concentrations [1,24,27]. Preliminary assays of the gentamicin antibiotic on axenic protist cultures indicated that gentamicin did not directly affect protist growth (electronic supplementary material, figure S2).…”

The antimicrobial and antibiofilm activities of copper(II) complexes

“…Often the resistance of biofilms towards antibiotics may be as much as 100-1000 fold higher than that of planktonic cells [4], and sub-inhibitory concentrations of certain antibiotics may even induce biofilm formation [5]. Several factors play a role in this including an altered physiological state, slow growth rate of bacteria in biofilms [3] and a limited penetration of antibiotics through biofilms [6,7].…”