The metabolic adaptation in response to nitrate Is critical for Actinobacillus pleuropneumoniae growth and pathogenicity under the regulation of NarQ/P
File(s)
Author(s)
Type
Journal Article
Abstract
Nitrate metabolism is an adaptation mechanism used by many bacteria for survival in anaerobic environments. As a by-product of inflammation, nitrate is used by the intestinal bacterial pathogens to enable gut infection. However, the responses of bacterial respiratory pathogens to nitrate are less well understood. Actinobacillus pleuropneumoniae is an important bacterial respiratory pathogen of swine. Previous studies have suggested that adaptation of A. pleuropneumoniae to anaerobiosis is important for infection. In this work, A. pleuropneumoniae growth and pathogenesis in response to the nitrate were investigated. Nitrate significantly promoted A. pleuropneumoniae growth under anaerobic conditions in vitro and lethality in mice. By using narQ and narP deletion mutants and single-residue-mutated complementary strains of ΔnarQ, the two-component system NarQ/P was confirmed to be critical for nitrate-induced growth, with Arg50 in NarQ as an essential functional residue. Transcriptome analysis showed that nitrate upregulated multiple energy-generating pathways, including nitrate metabolism, mannose and pentose metabolism, and glycerolipid metabolism via the regulation of NarQ/P. Furthermore, narQ, narP, and its target gene encoding the nitrate reductase Nap contributed to the pathogenicity of A. pleuropneumoniae. The Nap inhibitor tungstate significantly reduced the survival of A. pleuropneumoniae in vivo, suggesting that Nap is a potential drug target. These results give new insights into how the respiratory pathogen A. pleuropneumoniae utilizes the alternative electron acceptor nitrate to overcome the hypoxia microenvironment, which can occur in the inflammatory or necrotic infected tissues.
Date Issued
2022-08-08
Date Acceptance
2022-07-18
Citation
Infection and Immunity, 2022, 90 (9), pp.1-17
ISSN
0019-9567
Publisher
American Society for Microbiology
Start Page
1
End Page
17
Journal / Book Title
Infection and Immunity
Volume
90
Issue
9
Copyright Statement
© 2022 American Society for
Microbiology. All Rights Reserved.
Microbiology. All Rights Reserved.
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000838140000001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
nitrate
Actinobacillus pleuropneumoniae
growth
pathogenicity
regulation
NarP
NarQ
ENTERICA SEROVAR TYPHIMURIUM
ESCHERICHIA-COLI
GENE-EXPRESSION
NITRIC-OXIDE
REDUCTASE
VIRULENCE
IDENTIFICATION
INFLAMMATION
NARX
COLONIZATION
Publication Status
Published
Date Publish Online
2022-08-08