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Klebsiella pneumoniae type VI secretion system-mediated microbial competition is PhoPQ controlled and reactive oxygen species dependent

Storey, Daniel; McNally, Alan; �strand, Mia; sa-Pessoa Graca Santos, Joana; Rodriguez-Escudero, Isabel; Elmore, Bronagh; Palacios, Leyre; Marshall, Helina; Hobley, Laura; Molina, Maria; Cid, Victor J.; Salminen, Tiina A.; Bengoechea, Jose A.

Klebsiella pneumoniae type VI secretion system-mediated microbial competition is PhoPQ controlled and reactive oxygen species dependent Thumbnail


Authors

Daniel Storey

Alan McNally

Mia �strand

Joana sa-Pessoa Graca Santos

Isabel Rodriguez-Escudero

Bronagh Elmore

Leyre Palacios

Helina Marshall

Maria Molina

Victor J. Cid

Tiina A. Salminen

Jose A. Bengoechea



Contributors

Matthew R. Parsek
Editor

Abstract

Copyright: © 2020 Storey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Klebsiella pneumoniae is recognized as an urgent threat to human health due to the increasing isolation of multidrug resistant strains. Hypervirulent strains are a major concern due to their ability to cause life-threating infections in healthy hosts. The type VI secretion system (T6SS) is widely implicated in microbial antagonism, and it mediates interactions with host eukaryotic cells in some cases. In silico search for genes orthologous to T6SS component genes and T6SS effector genes across 700 K. pneumoniae genomes shows extensive diversity in T6SS genes across the K. pneumoniae species. Temperature, oxygen tension, pH, osmolarity, iron levels, and NaCl regulate the expression of the T6SS encoded by a hypervirulent K. pneumoniae strain. Polymyxins and human defensin 3 also increase the activity of the T6SS. A screen for regulators governing T6SS uncover the correlation between the transcription of the T6SS and the ability to kill E. coli prey. Whereas H-NS represses the T6SS, PhoPQ, PmrAB, Hfq, Fur, RpoS and RpoN positively regulate the T6SS. K. pneumoniae T6SS mediates intra and inter species bacterial competition. This antagonism is only evident when the prey possesses an active T6SS. The PhoPQ two component system governs the activation of K. pneumoniae T6SS in bacterial competitions. Mechanistically, PhoQ periplasmic domain, and the acid patch within, is essential to activate K. pneumoniae T6SS. Klebsiella T6SS also mediates anti-fungal competition. We have delineated the contribution of each of the individual VgrGs in microbial competition and identified VgrG4 as a T6SS effector. The DUF2345 domain of VgrG4 is sufficient to intoxicate bacteria and yeast. ROS generation mediates the antibacterial effects of VgrG4, and the antitoxin Sel1E protects against the toxic activity of VgrG4. Our findings provide a better understanding of the regulation of the T6SS in bacterial competitions, and place ROS as an early event in microbial competition.

Citation

Storey, D., McNally, A., Åstrand, M., sa-Pessoa Graca Santos, J., Rodriguez-Escudero, I., Elmore, B., …Bengoechea, J. A. (2020). Klebsiella pneumoniae type VI secretion system-mediated microbial competition is PhoPQ controlled and reactive oxygen species dependent. PLoS Pathogens, 16(3), Article e1007969. https://doi.org/10.1371/journal.ppat.1007969

Journal Article Type Article
Acceptance Date Feb 17, 2020
Online Publication Date Mar 19, 2020
Publication Date Mar 19, 2020
Deposit Date Jul 27, 2020
Publicly Available Date Jul 28, 2020
Journal PLoS Pathogens
Print ISSN 1553-7366
Electronic ISSN 1553-7374
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 16
Issue 3
Article Number e1007969
DOI https://doi.org/10.1371/journal.ppat.1007969
Keywords Immunology; Genetics; Molecular Biology; Microbiology; Parasitology; Virology
Public URL https://nottingham-repository.worktribe.com/output/4176411
Publisher URL https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007969#sec002

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