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


Blodkamp, Stefanie; Kadlec, Kristina; Gutsmann, Thomas; Quiblier, Chantal; Naim, Hassan Y; Schwarz, Stefan; von Köckritz-Blickwede, Maren (2017). Effects of SecDF on the antimicrobial functions of cathelicidins against Staphylococcus aureus. Veterinary Microbiology, 200:52-58.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2017
Deposited On:15 Dec 2016 10:46
Last Modified:22 Feb 2017 02:02
Publisher:Elsevier
ISSN:0378-1135
Publisher DOI:https://doi.org/10.1016/j.vetmic.2016.03.021
PubMed ID:27062479

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