Loss of rpoE Encoding the δ-Factor of RNA Polymerase Impacts Pathophysiology of the Streptococcus pyogenes M1T1 Strain 5448

dc.contributor.authorRom, Joseph S.
dc.contributor.authorLe Breton, Yoann
dc.contributor.authorIslam, Emrul
dc.contributor.authorBelew, Ashton T.
dc.contributor.authorEl-Sayed, Najib M.
dc.contributor.authorMcIver, Kevin S.
dc.date.accessioned2023-10-19T17:33:24Z
dc.date.available2023-10-19T17:33:24Z
dc.date.issued2022-08-22
dc.description.abstractStreptococcus pyogenes, also known as the Group A Streptococcus (GAS), is a Gram-positive bacterial pathogen of major clinical significance. Despite remaining relatively susceptible to conventional antimicrobial therapeutics, GAS still causes millions of infections and hundreds of thousands of deaths each year worldwide. Thus, a need for prophylactic and therapeutic interventions for GAS is in great demand. In this study, we investigated the importance of the gene encoding the delta (δ) subunit of the GAS RNA polymerase, rpoE, for its impact on virulence during skin and soft-tissue infection. A defined 5448 mutant with an insertionally-inactivated rpoE gene was defective for survival in whole human blood and was attenuated for both disseminated lethality and lesion size upon mono-culture infection in mouse soft tissue. Furthermore, the mutant had reduced competitive fitness when co-infected with wild type (WT) 5448 in the mouse model. We were unable to attribute this attenuation to any observable growth defect, although colony size and the ability to grow at higher temperatures were both affected when grown with nutrient-rich THY media. RNA-seq of GAS grown in THY to late log phase found that mutation of rpoE significantly impacted (>2-fold) the expression of 429 total genes (205 upregulated, 224 downregulated), including multiple virulence and “housekeeping” genes. The arc operon encoding the arginine deiminase (ADI) pathway was the most upregulated in the rpoE mutant and this could be confirmed phenotypically. Taken together, these findings demonstrate that the delta (δ) subunit of RNA polymerase is vital in GAS gene expression and virulence.
dc.description.urihttps://doi.org/10.3390/microorganisms10081686
dc.identifierhttps://doi.org/10.13016/dspace/15xd-4ozy
dc.identifier.citationRom, J.S.; Le Breton, Y.; Islam, E.; Belew, A.T.; El-Sayed, N.M.; McIver, K.S. Loss of rpoE Encoding the δ-Factor of RNA Polymerase Impacts Pathophysiology of the Streptococcus pyogenes M1T1 Strain 5448. Microorganisms 2022, 10, 1686.
dc.identifier.urihttp://hdl.handle.net/1903/31075
dc.language.isoen_US
dc.publisherMDPI
dc.relation.isAvailableAtCell Biology & Molecular Geneticsen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtCollege of Computer, Mathematical & Natural Sciencesen_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.subjectstreptococcus pyogenes
dc.subjectGAS
dc.subjectrpoE
dc.subjectvirulence
dc.subjectRNA-seq
dc.subjectarcA
dc.titleLoss of rpoE Encoding the δ-Factor of RNA Polymerase Impacts Pathophysiology of the Streptococcus pyogenes M1T1 Strain 5448
dc.typeArticle
local.equitableAccessSubmissionNo

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