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Title: Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women

Abstract

ABSTRACT Neisseria gonorrhoeaeis a bacterial pathogen responsible for the sexually transmitted infection gonorrhea. Emergence of antimicrobial resistance (AMR) ofN. gonorrhoeaeworldwide has resulted in limited therapeutic choices for this infection. Men who seek treatment often have symptomatic urethritis; in contrast, gonococcal cervicitis in women is usually minimally symptomatic, but may progress to pelvic inflammatory disease. Previously, we reported the first analysis of gonococcal transcriptome expression determined in secretions from women with cervical infection. Here, we defined gonococcal global transcriptional responses in urethral specimens from men with symptomatic urethritis and compared these with transcriptional responses in specimens obtained from women with cervical infections andin vitro-grownN. gonorrhoeaeisolates. This is the first comprehensive comparison of gonococcal gene expression in infected men and women. RNA sequencing analysis revealed that 9.4% of gonococcal genes showed increased expression exclusively in men and included genes involved in host immune cell interactions, while 4.3% showed increased expression exclusively in women and included phage-associated genes. Infected men and women displayed comparable antibiotic-resistant genotypes andin vitrophenotypes, but a 4-fold higher expression of the Mtr efflux pump-related genes was observed in men. These results suggest that expression of AMR genes is programed genotypically and also driven by sex-specific environments. Collectively, our results indicate thatmore » distinctN. gonorrhoeaegene expression signatures are detected during genital infection in men and women. We propose that therapeutic strategies could target sex-specific differences in expression of antibiotic resistance genes. IMPORTANCERecent emergence of antimicrobial resistance ofNeisseria gonorrhoeaeworldwide has resulted in limited therapeutic choices for treatment of infections caused by this organism. We performed global transcriptomic analysis ofN. gonorrhoeaein subjects with gonorrhea who attended a Nanjing, China, sexually transmitted infection (STI) clinic, where antimicrobial resistance ofN. gonorrhoeaeis high and increasing. We found thatN. gonorrhoeaetranscriptional responses to infection differed in genital specimens taken from men and women, particularly antibiotic resistance gene expression, which was increased in men. These sex-specific findings may provide a new approach to guide therapeutic interventions and preventive measures that are also sex specific while providing additional insight to address antimicrobial resistance ofN. gonorrhoeae.« less

Authors:
ORCiD logo; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1503578
Report Number(s):
PNNL-SA-138245
Journal ID: ISSN 2379-5042
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
mSphere
Additional Journal Information:
Journal Volume: 3; Journal Issue: 3; Journal ID: ISSN 2379-5042
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
RNA-seq, human mucosal infection, neisseria gonorrhoeae, antibiotic resistance

Citation Formats

Nudel, Kathleen, McClure, Ryan, Moreau, Matthew, Briars, Emma, Abrams, A. Jeanine, Tjaden, Brian, Su, Xiao-Hong, Trees, David, Rice, Peter A., Massari, Paola, Genco, Caroline A., and D'Orazio, Sarah E. F. Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women. United States: N. p., 2018. Web. doi:10.1128/mSphereDirect.00312-18.
Nudel, Kathleen, McClure, Ryan, Moreau, Matthew, Briars, Emma, Abrams, A. Jeanine, Tjaden, Brian, Su, Xiao-Hong, Trees, David, Rice, Peter A., Massari, Paola, Genco, Caroline A., & D'Orazio, Sarah E. F. Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women. United States. doi:10.1128/mSphereDirect.00312-18.
Nudel, Kathleen, McClure, Ryan, Moreau, Matthew, Briars, Emma, Abrams, A. Jeanine, Tjaden, Brian, Su, Xiao-Hong, Trees, David, Rice, Peter A., Massari, Paola, Genco, Caroline A., and D'Orazio, Sarah E. F. Wed . "Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women". United States. doi:10.1128/mSphereDirect.00312-18.
@article{osti_1503578,
title = {Transcriptome Analysis of Neisseria gonorrhoeae during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women},
author = {Nudel, Kathleen and McClure, Ryan and Moreau, Matthew and Briars, Emma and Abrams, A. Jeanine and Tjaden, Brian and Su, Xiao-Hong and Trees, David and Rice, Peter A. and Massari, Paola and Genco, Caroline A. and D'Orazio, Sarah E. F.},
abstractNote = {ABSTRACT Neisseria gonorrhoeaeis a bacterial pathogen responsible for the sexually transmitted infection gonorrhea. Emergence of antimicrobial resistance (AMR) ofN. gonorrhoeaeworldwide has resulted in limited therapeutic choices for this infection. Men who seek treatment often have symptomatic urethritis; in contrast, gonococcal cervicitis in women is usually minimally symptomatic, but may progress to pelvic inflammatory disease. Previously, we reported the first analysis of gonococcal transcriptome expression determined in secretions from women with cervical infection. Here, we defined gonococcal global transcriptional responses in urethral specimens from men with symptomatic urethritis and compared these with transcriptional responses in specimens obtained from women with cervical infections andin vitro-grownN. gonorrhoeaeisolates. This is the first comprehensive comparison of gonococcal gene expression in infected men and women. RNA sequencing analysis revealed that 9.4% of gonococcal genes showed increased expression exclusively in men and included genes involved in host immune cell interactions, while 4.3% showed increased expression exclusively in women and included phage-associated genes. Infected men and women displayed comparable antibiotic-resistant genotypes andin vitrophenotypes, but a 4-fold higher expression of the Mtr efflux pump-related genes was observed in men. These results suggest that expression of AMR genes is programed genotypically and also driven by sex-specific environments. Collectively, our results indicate that distinctN. gonorrhoeaegene expression signatures are detected during genital infection in men and women. We propose that therapeutic strategies could target sex-specific differences in expression of antibiotic resistance genes. IMPORTANCERecent emergence of antimicrobial resistance ofNeisseria gonorrhoeaeworldwide has resulted in limited therapeutic choices for treatment of infections caused by this organism. We performed global transcriptomic analysis ofN. gonorrhoeaein subjects with gonorrhea who attended a Nanjing, China, sexually transmitted infection (STI) clinic, where antimicrobial resistance ofN. gonorrhoeaeis high and increasing. We found thatN. gonorrhoeaetranscriptional responses to infection differed in genital specimens taken from men and women, particularly antibiotic resistance gene expression, which was increased in men. These sex-specific findings may provide a new approach to guide therapeutic interventions and preventive measures that are also sex specific while providing additional insight to address antimicrobial resistance ofN. gonorrhoeae.},
doi = {10.1128/mSphereDirect.00312-18},
journal = {mSphere},
issn = {2379-5042},
number = 3,
volume = 3,
place = {United States},
year = {2018},
month = {6}
}