Sökning: L773:2161 2129 >
Gonococcal Clinical...
Gonococcal Clinical Strains Bearing a Common gdhR Single Nucleotide Polymorphism That Results in Enhanced Expression of the Virulence Gene lctP Frequently Possess a mtrR Promoter Mutation That Decreases Antibiotic Susceptibility
-
- Ayala, Julio C. (författare)
- Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA
-
- Schmerer, Matthew W. (författare)
- STD Laboratory Reference and Research Branch, Division of STD Prevention, NCHHSTP, Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA
-
- Kersh, Ellen N. (författare)
- STD Laboratory Reference and Research Branch, Division of STD Prevention, NCHHSTP, Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA
-
visa fler...
-
- Unemo, Magnus, 1970- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology
-
- Shafer, William M. (författare)
- Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; Emory Antibiotic Resistance Center, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center, Decatur, Georgia, USA
-
visa färre...
-
Department of Microbiology and Immunology, Emory University School of Medicinegrid471395.d, Atlanta, Georgia, USA STD Laboratory Reference and Research Branch, Division of STD Prevention, NCHHSTP, Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA (creator_code:org_t)
- American Society for Microbiology, 2022
- 2022
- Engelska.
-
Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 13:2
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- GdhR is a transcriptional repressor of the virulence factor gene lctP, which encodes a unique l-lactate permease that has been linked to pathogenesis of Neisseria gonorrhoeae, and loss of gdhR can confer increased fitness of gonococci in a female mouse model of lower genital tract infection. In this work, we identified a single nucleotide polymorphism (SNP) in gdhR, which is often present in both recent and historical gonococcal clinical strains and results in a proline (P)-to-serine (S) change at amino acid position 6 (P6S) of GdhR. This mutation (gdhR6) was found to reduce GdhR transcriptional repression at lctP in gonococcal strains containing the mutant protein compared to wild-type GdhR. By using purified recombinant proteins and in vitro DNA-binding and cross-linking experiments, we found that gdhR6 impairs the DNA-binding activity of GdhR at lctP without an apparent effect on protein oligomerization. By analyzing a panel of U.S. (from 2017 to 2018) and Danish (1928 to 2013) clinical isolates, we observed a statistical association between gdhR6 and the previously described adenine deletion in the promoter of mtrR (mtrR-P A-del), encoding the repressor (MtrR) of the mtrCDE operon that encodes the MtrCDE multidrug efflux pump that can export antibiotics, host antimicrobials, and biocides. The frequent association of gdhR6 with the mtrR promoter mutation in these clinical isolates suggests that it has persisted in this genetic background to enhance lctP expression, thereby promoting virulence. IMPORTANCE We report the frequent appearance of a novel SNP in the gdhR gene (gdhR6) possessed by Neisseria gonorrhoeae. The resulting amino acid change in the GdhR protein resulted in enhanced expression of a virulence gene (lctP) that has been suggested to promote gonococcal survival during infection. The mutant GdhR protein expressed by gdhR6 had a reduced ability to bind to its target DNA sequence upstream of lctP. Interestingly, gdhR6 was found in clinical gonococcal strains isolated in the United States and Denmark at a high frequency and was frequently associated with a mutation in the promoter of the gene encoding a repressor (MtrR) of both the mtrCDE antimicrobial efflux pump operon and gdhR. Given this frequent association and the known impact of these regulatory mutations, we propose that virulence and antibiotic resistance properties are often phenotypically linked in contemporary gonococcal strains.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- Neisseria gonorrhoeae
- antibiotic resistance
- gdhR
- lctP
- mtrR
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
-
mBio
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas