Salmonella Typhimurium outer membrane protein A (OmpA) renders protection from nitrosative stress of macrophages by maintaining the stability of bacterial outer membrane

Bacterial porins are highly conserved outer membrane proteins used in the selective transport of charged molecules across the membrane. In addition to their significant contributions to the pathogenesis of Gram-negative bacteria, their role(s) in salmonellosis remains elusive. In this study, we inve...

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Bibliographic Details
Published in:PLoS pathogens 2022-08, Vol.18 (8), p.e1010708-e1010708
Main Authors: Roy Chowdhury, Atish, Sah, Shivjee, Varshney, Umesh, Chakravortty, Dipshikha
Format: Article
Language:English
Subjects:
Bacteria
Biology and Life Sciences
Chemical properties
Cytosol
E coli
Gram-negative bacteria
In vivo methods and tests
Infections
Influence
Intermediates
LAMP-1 protein
Macrophages
Medicine and Health Sciences
Membrane proteins
Membranes
Nitrotyrosine
Outer membrane proteins
Pathogenesis
Permeability
Physical Sciences
Physiological aspects
Porins
Porosity
Protein A
Proteins
Reactive nitrogen species
Salmonella
Salmonella Typhimurium
Salmonellosis
Sensitivity enhancement
Stress
Stress (Physiology)
Virulence
Virulence factors
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Summary:Bacterial porins are highly conserved outer membrane proteins used in the selective transport of charged molecules across the membrane. In addition to their significant contributions to the pathogenesis of Gram-negative bacteria, their role(s) in salmonellosis remains elusive. In this study, we investigated the role of outer membrane protein A (OmpA), one of the major outer membrane porins of Salmonella , in the pathogenesis of Salmonella Typhimurium (STM). Our study revealed that OmpA plays an important role in the intracellular virulence of Salmonella . An ompA deficient strain of Salmonella (STM ΔompA ) showed compromised proliferation in macrophages. We found that the SPI-2 encoded virulence factors such as sifA and ssaV are downregulated in STM ΔompA . The poor colocalization of STM ΔompA with LAMP-1 showed that disruption of SCV facilitated its release into the cytosol of macrophages, where it was assaulted by reactive nitrogen intermediates (RNI). The enhanced recruitment of nitrotyrosine on the cytosolic population of STM ΔompAΔsifA and ΔompAΔssaV compared to STM ΔsifA and ΔssaV showed an additional role of OmpA in protecting the bacteria from host nitrosative stress. Further, we showed that the generation of greater redox burst could be responsible for enhanced sensitivity of STM ΔompA to the nitrosative stress. The expression of several other outer membrane porins such as ompC , ompD , and ompF was upregulated in STM ΔompA . We found that in the absence of ompA , the enhanced expression of ompF increased the outer membrane porosity of Salmonella and made it susceptible to in vitro and in vivo nitrosative stress. Our study illustrates a novel mechanism for the strategic utilization of OmpA by Salmonella to protect itself from the nitrosative stress of macrophages.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1010708