Antibiotics as intermicrobial signaling agents instead of weapons

Abstract

It has been widely assumed that the ecological function of antibiotics in nature is fighting against competitors. This made them a good example of the Darwinian struggle-for-life in the microbial world. Based on this idea, it also has been believed that antibiotics, even at subinhibitory concentrations, reduce virulence of bacterial pathogens. Herein, using a combination of genomic and functional assays, we demonstrate that specific antibiotics (namely tobramycin, tetracycline, and norfloxacin) at subinhibitory concentrations trigger expression of determinants influencing the virulence of the major opportunistic bacterial pathogen Pseudomonas aeruginosa. All three antibiotics induce biofilm formation; tobramycin increases bacterial motility, and tetracycline triggers expression of P. aeruginosa type III secretion system and consequently bacterial cytotoxicity. Besides their relevance in the infection process, those determinants are relevant for the ecological behavior of this bacterial species in natural, nonclinical environments, either by favoring colonization of surfaces (biofilm, motility) or for fighting against eukaryotic predators (cytotoxicity). Our results support the notion that antibiotics are not only bacterial weapons for fighting competitors but also signaling molecules that may regulate the homeostasis of microbial communities. At low concentrations, they can even be beneficial for the behavior of susceptible bacteria in natural environments. This is a complete change on our vision on the ecological function of antibiotics with clear implications both for the treatment of infectious diseases and for the understanding of the microbial relationships in the biosphere. environment ͉ hormesis ͉ signals ͉ antibiotics ͉ Pseudomonas aeruginosa

Socially mediated induction and suppression of antibiosis during bacterial coexistence

“…Our results on randomly chosen streptomycetes from a single soil sample provide little support for the notion that antibiotics are cooperative signals used to coordinate bacterial behaviors (11,12) and instead support the classic idea that these agents are used to mediate competition (9,31). In addition, our data reveal that the classical dichotomy between killing and resistance used to understand interference competition between microbes is insufficient to describe interactions driven by antibiotics.…”

“…Although the antibiotics they produce have classically been viewed as intermicrobial weapons (6,9), this perspective is increasingly questioned on two grounds (10)(11)(12)(13). First, antibiotic concentrations in soil are believed to be too low to kill or inhibit competing bacteria (9).…”

“…Second, subinhibitory (sub-MIC) concentrations of antibiotics induce responses in exposed organisms, such as increased biofilm formation (14) or expression of virulence genes (11,15) that may benefit these target cells (10). Thus, rather than weapons, these arguments have led to the idea that antibiotics are cooperative signals (16) used for intercellular communication, that they are "collective regulators of the homeostasis of microbial communities" (12).…”

Enzymatic resistance to the lipopeptide surfactin as identified through imaging mass spectrometry of bacterial competition

“…Natural products benefit producing bacteria through signaling and inhibitory functions toward competitor bacteria (7)(8)(9). However, many of these metabolites provide a powerful selection for resistance to emerge within bacterial communities.…”

Antibiotiques et réponse SOS bactérienne

“…Les bactéries dormantes représenteraient au sein d'un biofilm les individus résistants. Bien que plusieurs antibiotiques (CIP, tobramycine et TCN) augmentent la formation de biofilm par Pseudomonas aeruginosa [26], il n'a toutefois pas été clairement démontré à ce jour que la réponse SOS pouvait jouer un rôle dans l'induction de la formation de biofilm bactérien.…”