The Rcs Stress Response System Regulator GumB Modulates Serratia marcescens-Induced Inflammation and Bacterial Proliferation in a Rabbit Keratitis Model and Cytotoxicity In Vitro

In this study, we tested the hypothesis that the conserved bacterial IgaA-family protein, GumB, mediates microbial pathogenesis associated with Serratia marcescens ocular infections through regulation of the Rcs stress response system. The role of the Rcs system and bacterial stress response systems...

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Bibliographic Details
Published in:Infection and immunity 2021-07, Vol.89 (8), p.e0011121-e0011121
Main Authors: Romanowski, Eric G, Stella, Nicholas A, Romanowski, John E, Yates, Kathleen A, Dhaliwal, Deepinder K, St Leger, Anthony J, Shanks, Robert M Q
Format: Article
Language:English
Subjects:
Animals
Bacterial Infections
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Gene Expression Regulation, Bacterial
Host-Pathogen Interactions
Keratitis - microbiology
Mutation
Rabbits
Serratia Infections - microbiology
Serratia marcescens - physiology
Stress, Physiological - genetics
Virulence
Virulence Factors - genetics
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Summary:In this study, we tested the hypothesis that the conserved bacterial IgaA-family protein, GumB, mediates microbial pathogenesis associated with Serratia marcescens ocular infections through regulation of the Rcs stress response system. The role of the Rcs system and bacterial stress response systems for microbial keratitis is not known, and the role of IgaA proteins in mammalian pathogenesis models has only been tested with partial-function allele variants of Salmonella. Here, we observed that an Rcs-activated mutant had a >50-fold reduction in proliferation compared to the wild type within rabbit corneas at 48 h and demonstrated a notable reduction in inflammation based on inflammatory signs, including the absence of hypopyons, and proinflammatory markers measured at the RNA and protein levels. The mutant phenotypes could be complemented by wild-type on a plasmid. We observed that bacteria with an inactivated Rcs stress response system induced high levels of ocular inflammation and restored corneal virulence to the mutant. The high virulence of the Δ mutant was dependent upon the ShlA cytolysin transporter ShlB. Similar results were found for testing the cytotoxic effects of wild-type and mutant bacteria on a human corneal epithelial cell line . Together, these data indicate that GumB regulates virulence factor production through the Rcs system, and this overall stress response system is a key mediator of a bacterium's ability to induce vision-threatening keratitis.
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00111-21