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

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.

doi:10.1128/mspheredirect.00312-18

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

Journal Article · Wed Jun 27 00:00:00 EDT 2018 · mSphere

DOI:https://doi.org/10.1128/mspheredirect.00312-18· OSTI ID:1773095

^[1]; McClure, Ryan ^[2]; Moreau, Matthew ^[1]; Briars, Emma ^[3]; Abrams, A. Jeanine ^[4]; Tjaden, Brian ^[5]; Su, Xiao-Hong ^[6]; Trees, David ^[4]; Rice, Peter A. ^[7]; Massari, Paola ^[1]; Genco, Caroline A. ^[1]

Tufts Univ., Boston, MA (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Boston Univ., MA (United States)
Centers for Disease Control and Prevention (CDC), Atlanta, GA (United States)
Wellesley College, MA (United States)
Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing (China). Nanjing STD Clinic
Univ. of Massachusetts Medical School, Worcester, MA (United States)

Neisseria gonorrhoeae is a bacterial pathogen responsible for the sexually transmitted infection gonorrhea. Emergence of antimicrobial resistance (AMR) of N. gonorrhoeae worldwide 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 and in vitro-grown N. gonorrhoeae isolates. 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 and in vitro phenotypes, 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 distinct N. gonorrhoeae gene 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.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1773095

Alternate ID(s):: OSTI ID: 1503578

Report Number(s):: PNNL-SA--127453

Journal Information:: mSphere, Journal Name: mSphere Journal Issue: 3 Vol. 3; ISSN 2379-5042

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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