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Comparative Study
. 2006 Dec 19;103(51):19484-9.
doi: 10.1073/pnas.0608949103. Epub 2006 Dec 5.

Antibiotics as intermicrobial signaling agents instead of weapons

J F Linares  1 , I Gustafsson, F Baquero, J L Martinez
Affiliations
Comparative Study

Antibiotics as intermicrobial signaling agents instead of weapons

J F Linares et al. Proc Natl Acad Sci U S A. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Effect of antibiotics on biofilm formation and motility of P. aeruginosa. (a) The effects of different concentrations of antibiotics (tobramycin, Left; tetracycline, Center; ciprofloxacin; Right) on the formation of static biofilms was measured as described in ref. . Red, planktonic growth; black, growth-forming biofilm. The mean value and standard deviations of eight different replicates are shown. Standard deviation bar is not shown when its size was lower than the size of the symbol in the graph. The arrows indicate the concentrations of antibiotics used for the experiments with microarrays. (b) Effect of antibiotics in P. aeruginosa motility. Swarming (Upper) and swimming (Lower) motility was measured as described in ref. . Growth culture media were different as the one used in the biofilm assay and the experiments with microarrays, and thus antibiotic concentrations also were different. The concentrations used were 0.015 mg/liter ciprofloxacin, 0.5 mg/liter tetracycline, and 0.25 mg/liter tobramycin.
Fig. 2.
Fig. 2.
Effect of tetracycline on the expression of T3SS and the cytotoxicity of P. aeruginosa. (a) The effect of tetracycline on the expression of the T3SS genes exsA and exoS was estimated by semiquantitative RT-PCR as described in ref. , by using rpsL as a control of RNA load. (b) The effect of tetracycline on the cytotoxicity of P. aeruginosa on a macrophage cell line was measured as described in ref. . Three experiments, each one consisting of eight replicates are shown. For each assay, median values and standard deviations are presented. White, cytotoxicity of P. aeruginosa without antibiotics; gray, cytotoxicity of P. aeruginosa in the presence of tetracycline.
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References

    1. Waksman SA, Woodruff HB. J Bacteriol. 1940;40:581–600. - PMC - PubMed
    1. Hoffman LR, D'Argenio DA, MacCoss MJ, Zhang Z, Jones RA, Miller SI. Nature. 2005;436:1171–1175. - PubMed
    1. Gibson RL, Burns JL, Ramsey BW. Am J Respir Crit Care Med. 2003;168:918–951. - PubMed
    1. Zielenski J, Tsui LC. Annu Rev Genet. 1995;29:777–807. - PubMed
    1. Govan JR, Deretic V. Microbiol Rev. 1996;60:539–574. - PMC - PubMed

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