Inflammation Fuels Colicin Ib-Dependent Competition of Salmonella Serovar Typhimurium and E. coli in Enterobacterial Blooms

Nedialkova, Lubov Petkova; Denzler, Remy; Koeppel, Martin B.; Diehl, Manuel; Ring, Diana; Wille, Thorsten; Gerlach, Roman G. und Stecher, Bärbel (2014): Inflammation Fuels Colicin Ib-Dependent Competition of Salmonella Serovar Typhimurium and E. coli in Enterobacterial Blooms.
In: PLOS Pathogens 10(1), e1003844

Abstract

The host's immune system plays a key role in modulating growth of pathogens and the intestinal microbiota in the gut. In particular, inflammatory bowel disorders and pathogen infections induce shifts of the resident commensal microbiota which can result in overgrowth of Enterobacteriaceae (inflammation-inflicted blooms). Here, we investigated competition of the human pathogenic Salmonella enterica serovar Typhimurium strain SL1344 (S. Tm) and commensal E. coli in inflammation-inflicted blooms. S. Tm produces colicin Ib (ColIb),which is a narrow-spectrum protein toxin active against related Enterobacteriaceae. Production of ColIb conferred a competitive advantage to S. Tm over sensitive E. coli strains in the inflamed gut. In contrast, an avirulent S. Tm mutant strain defective in triggering gut inflammation did not benefit from ColIb. Expression of ColIb (cib) is regulated by iron limitation and the SOS response. CirA, the cognate outer membrane receptor of ColIb on colicin-sensitive E. coli, is induced upon iron limitation. We demonstrate that growth in inflammation-induced blooms favours expression of both S. Tm ColIb and the receptor CirA, thereby fuelling ColIb dependent competition of S. Tm and commensal E. coli in the gut. In conclusion, this study uncovers a so-far unappreciated role of inflammation-inflicted blooms as an environment favouring ColIb-dependent competition of pathogenic and commensal representatives of the Enterobacteriaceae family. Author Summary Colicins are bacterial protein toxins which show potent activity against sensitive strains in vitro. Ecological models suggest that colicins play a major role in modulating dynamics of bacterial populations in the gut. However, previous studies could not readily confirm these predictions by respective in vivo experiments. In animal models, colicin-producing strains only show a minor or even absent fitness benefit over sensitive competitors. Here, we propose that the gut environment plays a crucial role in generating conditions for bacterial competition by colicin Ib (ColIb). Gut inflammation favours overgrowth of Enterobacteriaceae (inflammation-inflicted Enterobacterial blooms). We show that a pathogenic Salmonella Typhimurium (S. Tm) strain benefits from ColIb production in competition against commensal E. coli upon growth in inflammation-inflicted blooms. In the absence of gut inflammation, ColIb production did not confer a competitive advantage to S. Tm. In the inflamed gut, the genes for ColIb production in S. Tm and its corresponding ColIb-surface receptor CirA in E. coli were markedly induced, as compared to the non-inflamed gut. Therefore, environmental conditions in inflammation-inflicted blooms favour colicin-dependent competition of Enterobacteriaceae by triggering ColIb production and susceptibility at the same time. Our findings reveal a role of colicins as important bacterial fitness factors in inflammation-induced blooms.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Max-von-Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1553-7374
• Sprache: Englisch