Transcriptome Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women
ABSTRACT 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 u...
Guardado en:
| Autores principales: | , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
American Society for Microbiology
2018
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/355c292415414e6387a0346fd195fb2b |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:355c292415414e6387a0346fd195fb2b |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:355c292415414e6387a0346fd195fb2b2021-11-15T15:24:22ZTranscriptome Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women10.1128/mSphereDirect.00312-182379-5042https://doaj.org/article/355c292415414e6387a0346fd195fb2b2018-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00312-18https://doaj.org/toc/2379-5042ABSTRACT 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. IMPORTANCE Recent emergence of antimicrobial resistance of Neisseria gonorrhoeae worldwide has resulted in limited therapeutic choices for treatment of infections caused by this organism. We performed global transcriptomic analysis of N. gonorrhoeae in subjects with gonorrhea who attended a Nanjing, China, sexually transmitted infection (STI) clinic, where antimicrobial resistance of N. gonorrhoeae is high and increasing. We found that N. gonorrhoeae transcriptional 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 of N. gonorrhoeae.Kathleen NudelRyan McClureMatthew MoreauEmma BriarsA. Jeanine AbramsBrian TjadenXiao-Hong SuDavid TreesPeter A. RicePaola MassariCaroline A. GencoAmerican Society for MicrobiologyarticleNeisseria gonorrhoeaeRNA-seqantibiotic resistancehuman mucosal infectionMicrobiologyQR1-502ENmSphere, Vol 3, Iss 3 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Neisseria gonorrhoeae RNA-seq antibiotic resistance human mucosal infection Microbiology QR1-502 |
| spellingShingle |
Neisseria gonorrhoeae RNA-seq antibiotic resistance human mucosal infection Microbiology QR1-502 Kathleen Nudel Ryan McClure Matthew Moreau Emma Briars A. Jeanine Abrams Brian Tjaden Xiao-Hong Su David Trees Peter A. Rice Paola Massari Caroline A. Genco Transcriptome Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women |
| description |
ABSTRACT 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. IMPORTANCE Recent emergence of antimicrobial resistance of Neisseria gonorrhoeae worldwide has resulted in limited therapeutic choices for treatment of infections caused by this organism. We performed global transcriptomic analysis of N. gonorrhoeae in subjects with gonorrhea who attended a Nanjing, China, sexually transmitted infection (STI) clinic, where antimicrobial resistance of N. gonorrhoeae is high and increasing. We found that N. gonorrhoeae transcriptional 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 of N. gonorrhoeae. |
| format |
article |
| author |
Kathleen Nudel Ryan McClure Matthew Moreau Emma Briars A. Jeanine Abrams Brian Tjaden Xiao-Hong Su David Trees Peter A. Rice Paola Massari Caroline A. Genco |
| author_facet |
Kathleen Nudel Ryan McClure Matthew Moreau Emma Briars A. Jeanine Abrams Brian Tjaden Xiao-Hong Su David Trees Peter A. Rice Paola Massari Caroline A. Genco |
| author_sort |
Kathleen Nudel |
| title |
Transcriptome Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women |
| title_short |
Transcriptome Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women |
| title_full |
Transcriptome Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women |
| title_fullStr |
Transcriptome Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women |
| title_full_unstemmed |
Transcriptome Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> during Natural Infection Reveals Differential Expression of Antibiotic Resistance Determinants between Men and Women |
| title_sort |
transcriptome analysis of <named-content content-type="genus-species">neisseria gonorrhoeae</named-content> during natural infection reveals differential expression of antibiotic resistance determinants between men and women |
| publisher |
American Society for Microbiology |
| publishDate |
2018 |
| url |
https://doaj.org/article/355c292415414e6387a0346fd195fb2b |
| work_keys_str_mv |
AT kathleennudel transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen AT ryanmcclure transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen AT matthewmoreau transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen AT emmabriars transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen AT ajeanineabrams transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen AT briantjaden transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen AT xiaohongsu transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen AT davidtrees transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen AT peterarice transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen AT paolamassari transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen AT carolineagenco transcriptomeanalysisofnamedcontentcontenttypegenusspeciesneisseriagonorrhoeaenamedcontentduringnaturalinfectionrevealsdifferentialexpressionofantibioticresistancedeterminantsbetweenmenandwomen |
| _version_ |
1718427939917266944 |