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Ferrous iron-binding protein Omb of Salmonella enterica serovar Choleraesuis promotes resistance to hydrophobic antibiotics and contributes to its virulence

¹ Department of Biotechnology, Chia-Nan University of Pharmacy and Science. 2Department of Life Scienc;
² Department of Medical Research, Chi Mei Medical Center;
³ Department of Internal Medicine, National Cheng-Kung University Hospital;
⁴ Department of Life Science, College of Bioscience and Biotechnology, National Cheng-Kung University;
⁵ Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng-Kung Universit

ABSTRACT

Salmonella enterica serovar Choleraesuis (SC) is an important enteric pathogen that causes serious systemic infections in swine and humans. To identify the genes required for resistance to antimicrobial peptides, we constructed a bank of SC transposon mutants and screened them for hypersensitivity to the cationic peptide polymyxin B. Here we report one isolated polymyxin B-susceptible mutant that also exhibited increased sensitivity toward human neutrophil peptide alpha-defensin 1 (HNP-1) and hydrophobic antibiotics including erythromycin and novobiocin. The mutant had a mutation in an open reading frame identified as outer membrane β-barrel protein gene, omb. The purified recombinant Omb protein was characterized as a ferrous iron-binding protein. The constructed omb isogenic mutant grew slower in iron-limiting conditions than the wild-type (WT) parent strain. In addition, compared to the WT strain, the omb mutant exhibited an increase in net negative charge upon the cell surface and was more easily killed by polymyxin B, HNP-1, and by hydrophobic antibiotics. The omb gene was transcribed, regardless of the iron content within the growth medium, and the Omb protein appeared exclusively in the outer membrane fraction. The infection experiments demonstrated virulence attenuation when this mutant was administered orally or intraperitoneally to mice. This study indicates that Omb is a previously unrecognized ferrous iron-binding protein. In vivo, Omb may be involved in the acquisition of ferrous iron during the initial stages of SC infection and appears to be an important virulence factor for SC in mice.

⁶ E-mail: mcchang{at}mail.ncku.edu.tw