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ROLE OF VOLATILE COMPOUNDS IN BACTERIAL COMMUNITY BIOLOGY

Biogenic ammonia modifies antibiotic resistance at a distance

We showed that aerial exposure to volatile and diffusible gaseous ammonia modifies the antibiotic resistance pattern of distant recipient Gram-negative and Gram-positive bacteria, including Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus subtillis. We demonstrated that ammonia uptake enhance the intracellular production of polyamines, which subsequently led to transient, non-inherited modification of metabolism and modifications in antibiotic and oxidative stress resistance profiles in all tested, aerially exposed recipient bacteria (Fig.5). Ammonia therefore constitutes the first characterized volatile signal involved in long-range inter-bacterial chemical communication perception and could constitute a biotic cue allowing not only to modulate antibiotic resistance, but also to acquire competitive abilities in densely populated environments.

Volatile compounds are potentially ideal “infochemicals” able to be diffused in heterogeneous environments (soil, gut, etc.) colonized by bacteria. Our study demonstrates that volatile compounds can modify bacterial metabolism and affect bacterial biology and ecology in physically separated bacteria.

Bernier, S.; Létoffé, S. ; Delepierre, M and Ghigo J.M.. (2011)Biogenic ammonia modifies antibiotic resistance at a distance in physically separated bacteria. Molecular Microbiology 81:705-716.

"IN BIOFILM" METABOLISM AND ITS CONSEQUENCES

The amino-acid valine is secreted in continuous-flow bacterial biofilms.

Biofilms are structured communities characterized by distinctive gene expression patterns and profound physiological changes compared to those of planktonic cultures. Here, we show that many gram-negative bacterial biofilms secrete high levels of a small-molecular-weight compound, which inhibits the growth of only Escherichia coli K-12 and a rare few other natural isolates. We demonstrate both genetically and biochemically that this molecule is the amino acid valine, and we provide evidence that valine production within biofilms results from metabolic changes occurring within high-density biofilm communities when carbon sources are not limiting. This finding identifies a natural environment in which bacteria can encounter high amounts of valine, and we propose that in-biofilm valine secretion may be the long-sought reason for widespread but unexplained valine resistance found in most enterobacteria. Our results experimentally validate the postulated production of metabolites that is characteristic of the conditions associated with some biofilm environments. The identification of such molecules may lead to new approaches for biofilm monitoring and control.

Valle, J., Da Re, S., Schmid, S., Skurnik, D., D'Ari, R. and Ghigo, J. M. (2008) The amino acid valine is secreted in continuous-flow bacterial biofilms  J Bacteriol.190:264-74.

Identification of new anti-biofilm polysaccharides.

We hypothesisized that the biofilm lifestyle could trigger metabolic adjustments potentially leading to the production of biofilm-associated molecules involved in competitive or cooperative behaviors affecting population dynamics. We screened a large collection of natural strains representative of E. coli species biodiversity and we showed that anti-adhesion compounds, which are not detected in non-concentrated planktonic supernatants, are frequently found in mature biofilm extracts (Fig.4). One of these compounds corresponds to a new type of released high-molecular weight polysaccharide, which induces increased surface hydrophilicity and confers a competitive advantage to the producing strain against clinically relevant Gram-positive bacterial pathogens such as Staphylococus aureus. This study showed that bacterial biofilms constitute untapped sources of natural bioactive molecules antagonizing adhesion or biofilm formation of other bacteria. The exploration of the biofilm environment could therefore provide a better understanding of bacterial interactions within complex communities and could lead to the identification of compounds permitting improved control of pathogen colonization. A structure function analysis of the identified anti-biofilm polysaccharides is under way.

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• Rendueles, O. ; Travier, L. ; Latour-Lambert, P. ; Fontaine, T. ; Magnus, J. ; Denamur, E.  and Ghigo J.M. (2011) Screening Escherichia coli species biodiversity reveals new biofilm-associated anti-adhesion polysaccharides. mBio 00043-11.

Biofilm-specific LPS modifications in P. aeruginosa.

In collaboration with JM Cavaillon (IP- and Martine Caroff (Orsay, U. Paris XI), we compared the cytokine induction by planktonic and biofilm Pseudomonas aeruginosa bacteria and showed that biofilm-forming P. aeruginosa induced a higher production of tumor necrosis factor and interleukin-6 than their planktonic counterpart. We showed that the switch between planktonic to biofilm lifestyles caused several reversible LPS structure modifications affecting the lipid A and polysaccharide moieties inducing increase in inflammatory cytokines responses.

This study shows that, in addition to known phenotypes associated with the biofilm lifestyle, biofilm formation also induces LPS and lipid A structural modifications, which contribute to an increased inflammatory response caused by P. aeruginosa biofilms infections.

Ciornei, C. D., Novikov, A., Beloin, C., Fitting, C., Caroff, M., Ghigo, J. M., Cavaillon, J. M. and Adib-Conquy, M. (2010) Biofilm-forming Pseudomonas aeruginosa bacteria undergo lipopolysaccharide structural modifications and induce enhanced inflammatory cytokine response in human monocytes Innate Immun.16:288-301.