Deprivation of the periplasmic chaperone SurA reduces virulence and restores antibiotic susceptibility of multidrug-resistant pseudomonas aeruginosa

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Klein, K, Sonnabend, MS, Frank, L, Leibiger, K, Franz-Wachtel, M, Macek, B, Trunk, T, Leo, JC ORCID: https://orcid.org/0000-0002-7066-7527, Autenrieth, IB, Schütz, M and Bohn, E, 2019. Deprivation of the periplasmic chaperone SurA reduces virulence and restores antibiotic susceptibility of multidrug-resistant pseudomonas aeruginosa. Frontiers in Microbiology, 10: 100. ISSN 1664-302X

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Official URL: http://doi.org/10.3389/fmicb.2019.00100

Abstract

Pseudomonas aeruginosa is one of the main causative agents of nosocomial infections and the spread of multidrug-resistant strains is rising. Therefore, novel strategies for therapy are urgently required. The outer membrane composition of Gram-negative pathogens and especially of Pa restricts the efficacy of antibiotic entry into the cell and determines virulence. For efficient outer membrane protein biogenesis, the β-barrel assembly machinery (BAM) complex in the outer membrane and periplasmic chaperones like Skp and SurA are crucial. Previous studies indicated that the importance of individual proteins involved in outer membrane protein biogenesis may vary between different Gram-negative species. In addition, since multidrug-resistant Pa strains pose a serious global threat, the interference with both virulence and antibiotic resistance by disturbing outer membrane protein biogenesis might be a new strategy to cope with this challenge. Therefore, deletion mutants of the non-essential BAM complex components bamB and bamC, of the skp homolog hlpA as well as a conditional mutant of surA were investigated. The most profound effects for both traits were associated with reduced levels of SurA, characterized by increased membrane permeability, enhanced sensitivity to antibiotic treatment and attenuation of virulence in a Galleria mellonella infection model. Strikingly, the depletion of SurA in a multidrug-resistant clinical bloodstream isolate re-sensitized the strain to antibiotic treatment. From our data we conclude that SurA of Pa serves as a promising target for developing a drug that shows antiinfective activity and re-sensitizes multidrug-resistant strains to antibiotics.

Item Type:	Journal article
Publication Title:	Frontiers in Microbiology
Creators:	Klein, K., Sonnabend, M.S., Frank, L., Leibiger, K., Franz-Wachtel, M., Macek, B., Trunk, T., Leo, J.C., Autenrieth, I.B., Schütz, M. and Bohn, E.
Publisher:	Frontiers Media SA
Date:	21 February 2019
Volume:	10
ISSN:	1664-302X
Identifiers:	Number Type 10.3389/fmicb.2019.00100 DOI
Rights:	Copyright © 2019 Klein, Sonnabend, Frank, Leibiger, Franz-Wachtel, Macek, Trunk, Leo, Autenrieth, Schütz and Bohn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Divisions:	Schools > School of Science and Technology
Record created by:	Jill Tomkinson
Date Added:	17 Jun 2019 14:27
Last Modified:	25 Jun 2019 12:55
URI:	https://irep.ntu.ac.uk/id/eprint/36830