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Vet Microbiol. 2017 Feb;200:52-58. doi: 10.1016/j.vetmic.2016.03.021. Epub 2016 Mar 31.

Effects of SecDF on the antimicrobial functions of cathelicidins against Staphylococcus aureus.

Author information

1
Department of Physiological Chemistry, University of Veterinary Medicine, Hannover, Germany; Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Neustadt-Mariensee, Germany.
2
Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Neustadt-Mariensee, Germany.
3
Research group Biophysics, Research Centre Borstel, Borstel, Germany.
4
Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland.
5
Department of Physiological Chemistry, University of Veterinary Medicine, Hannover, Germany.
6
Institute of Farm Animal Genetics, Friedrich-Loeffler-Institut, Neustadt-Mariensee, Germany. Electronic address: stefan.schwarz@fli.bund.de.
7
Department of Physiological Chemistry, University of Veterinary Medicine, Hannover, Germany; Research Centre for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine, Hannover, Germany. Electronic address: mkoeckbl@tiho-hannover.de.

Abstract

Antimicrobial peptides (AMPs) represent an important part of the innate host immune system. Although they are active against a broad range of pathogens, bacteria have evolved different resistance mechanisms to avoid killing by AMPs. Since not much is known about the impact of efflux pumps on the susceptibility of Gram-positive bacteria to AMPs, especially to the cathelicidins, the aim of this study was to analyze whether Staphylococcus aureus can use efflux pumps to resist the antimicrobial effects of cathelicidins derived from different animal species (human, mouse, rabbit or cattle). For this purpose the minimal inhibitory concentrations (MICs) of S. aureus field isolates for the cathelicidins LL-37, mCRAMP, CAP18, BMAP-27 and BMAP-28 in the presence and absence of different efflux pump inhibitors were determined. Furthermore, the MICs of mutants lacking SecDF, a member of the RND efflux pump family, were determined and compared to the MICs of their respective wildtype and complemented strains. The data demonstrated that after blocking RND-type efflux pumps with 1-(1-naphthylmethyl)-piperazine, the MICs for CAP18, but not those for the other cathelicidins tested, were significantly decreased. In good correlation with these data, significantly decreased MICs for CAP18 and also BMAP-27 have been observed for SecDF knockout mutants as compared to their isogenic wildtype strains. In addition, the MIC values increased again after re-introducing a cloned secDF via plasmid complementation. These results indicated an involvement of SecDF in a reduced efficacy of species-specific cathelicidins against S. aureus.

KEYWORDS:

Antimicrobial peptides; Efflux pump inhibitors; Minimal inhibitory concentration (MIC); RND efflux pumps

PMID:
27062479
DOI:
10.1016/j.vetmic.2016.03.021
[Indexed for MEDLINE]

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