Elucidation of the RamA Regulon in Reveals a Role in LPS Regulation

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Bacteria can rapidly evolve under antibiotic pressure to develop resistance, which occurs when target genes mutate, or when resistance-encoding genes are transferred. Alternatively, microbes can simply alter the levels of intrinsic proteins that allow the organism to “buy” time to resist antibiotic pressure. Klebsiella pneumoniae is a pathogen that causes significant blood stream or respiratory infections, but more importantly is a bacterium that is increasingly being reported as multidrug resistant. Our data demonstrate that RamA can trigger changes on the bacterial surface that allow Klebsiella to survive both antibiotic challenge, degradation by host immune peptides and resist phagocytosis. We demonstrate that the molecular basis of increased survival of ramA overexpressing K. pneumoniae, against host-derived factors is associated with RamA-driven alterations of the lipid A moiety of Klebsiella LPS. This modification is likely to be linked to Klebsiella’s ability to resist the host response so that it remains undetected by the immune system. The relevance of our work extends beyond RamA in Klebsiella as other pathogens such as Enterobacter spp and Salmonella spp. also produce this protein. Thus our overarching conclusion is that the intrinsic regulator, RamA perturbs host-microbe and microbe-drug interactions.

Vyšlo v časopise: Elucidation of the RamA Regulon in Reveals a Role in LPS Regulation. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004627
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004627

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