Global Network Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection

ABSTRACT Neisseria gonorrhoeae is a Gram-negative diplococcus that is responsible for the sexually transmitted infection gonorrhea, a high-morbidity disease in the United States and worldwide. Over the past several years, N. gonorrhoeae strains resistant to antibiotics used to treat this infection h...

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Autores principales:	Ryan McClure, Ashwini Sunkavalli, Phillip M. Balzano, Paola Massari, Christine Cho, William M. Nauseef, Michael A. Apicella, Caroline A. Genco
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	RNA-seq Neisseria gonorrhoeae network analysis regulatory proteins transcriptomics global regulatory networks Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/28124aedf0a14ab78f9eacb2420e21da
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spelling	oai:doaj.org-article:28124aedf0a14ab78f9eacb2420e21da2021-12-02T19:47:34ZGlobal Network Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection10.1128/mSystems.00729-192379-5077https://doaj.org/article/28124aedf0a14ab78f9eacb2420e21da2020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00729-19https://doaj.org/toc/2379-5077ABSTRACT Neisseria gonorrhoeae is a Gram-negative diplococcus that is responsible for the sexually transmitted infection gonorrhea, a high-morbidity disease in the United States and worldwide. Over the past several years, N. gonorrhoeae strains resistant to antibiotics used to treat this infection have begun to emerge across the globe. Thus, new treatment strategies are needed to combat this organism. Here, we utilized N. gonorrhoeae transcriptomic data sets, including those obtained from natural infection of the human genital tract, to infer the first global gene coexpression network of this pathogen. Interrogation of this network revealed genes central to the network that are likely critical for gonococcal growth, metabolism, and virulence, including genes encoding hypothetical proteins expressed during mucosal infection. In addition, network analysis revealed overlap in the response of N. gonorrhoeae to incubation with neutrophils and exposure to hydrogen peroxide stress in vitro. Network analysis also identified new targets of the gonococcal global regulatory protein Fur, while examination of the network neighborhood of genes allowed us to assign additional putative categories to several proteins. Collectively, the characterization of the first gene coexpression network for N. gonorrhoeae described here has revealed new regulatory pathways and new categories for proteins and has shown how processes important to gonococcal infection in both men and women are linked. This information fills a critical gap in our understanding of virulence strategies of this obligate human pathogen and will aid in the development of new treatment strategies for gonorrhea. IMPORTANCE Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection (STI) gonorrhea, a disease with high morbidity worldwide with an estimated 87 million cases annually. Current therapeutic and pharmacologic approaches to treat gonorrhea have been compromised by increased antibiotic resistance worldwide, including to the most recent FDA-approved antibiotic. New treatment strategies are urgently needed to combat this organism. In this study, we used network analysis to interrogate and define the coordination of pathways and processes in N. gonorrhoeae. An analysis of the gonococcal network was also used to assign categories to genes and to expand our understanding of regulatory strategies. Network analysis provides important insights into pathogenic mechanisms of this organism that will guide the design of new strategies for disease treatment.Ryan McClureAshwini SunkavalliPhillip M. BalzanoPaola MassariChristine ChoWilliam M. NauseefMichael A. ApicellaCaroline A. GencoAmerican Society for MicrobiologyarticleRNA-seqNeisseria gonorrhoeaenetwork analysisregulatory proteinstranscriptomicsglobal regulatory networksMicrobiologyQR1-502ENmSystems, Vol 5, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	RNA-seq Neisseria gonorrhoeae network analysis regulatory proteins transcriptomics global regulatory networks Microbiology QR1-502
spellingShingle	RNA-seq Neisseria gonorrhoeae network analysis regulatory proteins transcriptomics global regulatory networks Microbiology QR1-502 Ryan McClure Ashwini Sunkavalli Phillip M. Balzano Paola Massari Christine Cho William M. Nauseef Michael A. Apicella Caroline A. Genco Global Network Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection
description	ABSTRACT Neisseria gonorrhoeae is a Gram-negative diplococcus that is responsible for the sexually transmitted infection gonorrhea, a high-morbidity disease in the United States and worldwide. Over the past several years, N. gonorrhoeae strains resistant to antibiotics used to treat this infection have begun to emerge across the globe. Thus, new treatment strategies are needed to combat this organism. Here, we utilized N. gonorrhoeae transcriptomic data sets, including those obtained from natural infection of the human genital tract, to infer the first global gene coexpression network of this pathogen. Interrogation of this network revealed genes central to the network that are likely critical for gonococcal growth, metabolism, and virulence, including genes encoding hypothetical proteins expressed during mucosal infection. In addition, network analysis revealed overlap in the response of N. gonorrhoeae to incubation with neutrophils and exposure to hydrogen peroxide stress in vitro. Network analysis also identified new targets of the gonococcal global regulatory protein Fur, while examination of the network neighborhood of genes allowed us to assign additional putative categories to several proteins. Collectively, the characterization of the first gene coexpression network for N. gonorrhoeae described here has revealed new regulatory pathways and new categories for proteins and has shown how processes important to gonococcal infection in both men and women are linked. This information fills a critical gap in our understanding of virulence strategies of this obligate human pathogen and will aid in the development of new treatment strategies for gonorrhea. IMPORTANCE Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection (STI) gonorrhea, a disease with high morbidity worldwide with an estimated 87 million cases annually. Current therapeutic and pharmacologic approaches to treat gonorrhea have been compromised by increased antibiotic resistance worldwide, including to the most recent FDA-approved antibiotic. New treatment strategies are urgently needed to combat this organism. In this study, we used network analysis to interrogate and define the coordination of pathways and processes in N. gonorrhoeae. An analysis of the gonococcal network was also used to assign categories to genes and to expand our understanding of regulatory strategies. Network analysis provides important insights into pathogenic mechanisms of this organism that will guide the design of new strategies for disease treatment.
format	article
author	Ryan McClure Ashwini Sunkavalli Phillip M. Balzano Paola Massari Christine Cho William M. Nauseef Michael A. Apicella Caroline A. Genco
author_facet	Ryan McClure Ashwini Sunkavalli Phillip M. Balzano Paola Massari Christine Cho William M. Nauseef Michael A. Apicella Caroline A. Genco
author_sort	Ryan McClure
title	Global Network Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection
title_short	Global Network Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection
title_full	Global Network Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection
title_fullStr	Global Network Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection
title_full_unstemmed	Global Network Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection
title_sort	global network analysis of <named-content content-type="genus-species">neisseria gonorrhoeae</named-content> identifies coordination between pathways, processes, and regulators expressed during human infection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/28124aedf0a14ab78f9eacb2420e21da
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Global Network Analysis of <named-content content-type="genus-species">Neisseria gonorrhoeae</named-content> Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection

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