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Both MisR (CpxR) and MisS (CpxA) Are Required for Neisseria gonorrhoeae Infection in a Murine Model of Lower Genital Tract Infection
- Source :
- Infection and immunity. 85(9)
- Publication Year :
- 2017
-
Abstract
- During infection, Neisseria gonorrhoeae senses and responds to stress; such responses may be modulated by MisRS (NGO0177 and NGO0176), a two-component system that is a homolog of CpxRA. In Escherichia coli , CpxRA senses and responds to envelope stress; CpxA is a sensor kinase/phosphatase for CpxR, a response regulator. When a cpxA mutant is grown in medium containing glucose, CpxR is phosphorylated by acetyl phosphate but cannot be dephosphorylated, resulting in constitutive activation. Kandler and coworkers (J. L. Kandler, C. L. Holley, J. L. Reimche, V. Dhulipala, J. T. Balthazar, A. Muszyński, R. W. Carlson, and W. M. Shafer, Antimicrob Agents Chemother 60:4690–4700, 2016, https://doi.org/10.1128/AAC.00823-16 ) showed that MisR (CpxR) is required for the maintenance of membrane integrity and resistance to antimicrobial peptides, suggesting a role in gonococcal survival in vivo . Here, we evaluated the contributions of MisR and MisS (CpxA) to gonococcal infection in a murine model of cervicovaginal colonization and identified MisR-regulated genes using RNA sequencing (RNA-Seq). The deletion of misR or misS severely reduced the capacity of N. gonorrhoeae to colonize mice or maintain infection over a 7-day period and reduced microbial fitness after exposure to heat shock. Compared to the wild type (WT), the inactivation of misR identified 157 differentially regulated genes, most of which encoded putative envelope proteins. The inactivation of misS identified 17 differentially regulated genes compared to the WT and 139 differentially regulated genes compared to the misR mutant, 111 of which overlapped those differentially expressed in the comparison of the WT versus the misR mutant. These data indicate that an intact MisRS system is required for gonococcal infection of mice. Provided the MisR is constitutively phosphorylated in the misS mutant, the data suggest that controlled but not constitutive activation is required for gonococcal infection in mice.
- Subjects :
- 0301 basic medicine
Virulence Factors
030106 microbiology
Immunology
Mutant
Phosphatase
Cervix Uteri
Biology
medicine.disease_cause
Microbiology
Regulon
Reproductive Tract Infections
03 medical and health sciences
Gonorrhea
Bacterial Proteins
medicine
Animals
Gene
Escherichia coli
Mice, Inbred BALB C
Kinase
Sequence Analysis, RNA
Gene Expression Profiling
Wild type
Gene Expression Regulation, Bacterial
Molecular Pathogenesis
Neisseria gonorrhoeae
Response regulator
Disease Models, Animal
Infectious Diseases
Vagina
Parasitology
Female
Protein Kinases
Gene Deletion
Signal Transduction
Subjects
Details
- ISSN :
- 10985522
- Volume :
- 85
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Infection and immunity
- Accession number :
- edsair.doi.dedup.....6c72ca728f803726ac890c6a51ea9fc5