Abstract

Antimicrobial peptides (APs) belong to the arsenal of weapons of the innate immune system against infections. In the case of gram-negative bacteria, APs interact with the anionic lipid A moiety of the lipopolysaccharide (LPS). In yersiniae most virulence factors are temperature regulated. Studies from our laboratory demonstrated that Yersinia enterocolitica is more susceptible to polymyxin B, a model AP, when grown at 37°C than at 22°C (J. A. Bengoechea, R. Díaz, and I. Moriyón, Infect. Immun. 64:4891-4899, 1996), and here we have extended this observation to other APs, not structurally related to polymyxin B. Mechanistically, we demonstrate that the lipid A modifications with aminoarabinose and palmitate are downregulated at 37°C and that they contribute to AP resistance together with the LPS O-polysaccharide. Bacterial loads of lipid A mutants in Peyer's patches, liver, and spleen of orogastrically infected mice were lower than those of the wild-type strain at 3 and 7 days postinfection. PhoPQ and PmrAB two-component systems govern the expression of the loci required to modify lipid A with aminoarabinose and palmitate, and their expressions are also temperature regulated. Our findings support the notion that the temperature-dependent regulation of loci controlling lipid A modifications could be explained by H-NS-dependent negative regulation alleviated by RovA. In turn, our data also demonstrate that PhoPQ and PmrAB regulate positively the expression of rovA, the effect of PhoPQ being more important. However, rovA expression reached wild-type levels in the phoPQ pmrAB mutant background, hence indicating the existence of an unknown regulatory network controlling rovA expression in this background.

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Authors

Reinés M, Llobet E, Llompart CM, Moranta D, Pérez-Gutiérrez C, Bengoechea JA

Institution

Laboratory Microbial Pathogenesis, Fundació d'Investigació Sanitària de les Illes Balears (FISIB), Recinto Hospital Joan March, Bunyola, Spain.

Source

Journal of bacteriology 194:12 2012 Jun pg 3173-88

MeSH

Animals
Antimicrobial Cationic Peptides
Arabinose
Bacterial Load
Bacterial Proteins
DNA-Binding Proteins
Disease Models, Animal
Drug Resistance, Bacterial
Gene Expression Regulation, Bacterial
Lipid A
Liver
Mice
O Antigens
Palmitates
Peyer's Patches
Polymyxin B
Spleen
Temperature
Transcription Factors
Yersinia Infections
Yersinia enterocolitica

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22505678