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Title: Global Network Analysis of Neisseria gonorrhoeae 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 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 processesmore » 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.« less

Authors:
 [1];  [2];  [2];  [2];  [3];  [3];  [3];  [2]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  2. Tufts Univ., Medford, MA (United States)
  3. Univ. of Iowa, Iowa City, IA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1600632
Report Number(s):
PNNL-SA-144073
Journal ID: ISSN 2379-5077
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
mSystems
Additional Journal Information:
Journal Volume: 5; Journal Issue: 1; Journal ID: ISSN 2379-5077
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; RNA-seq; neisseria gonorrhoeae; network analysis; regulators

Citation Formats

McClure, Ryan S., Sunkavalli, Ashwini, Balzano, Phillip, Massari, Paola, Cho, Christine, Nauseef, William M., Apicella, Michael A., and Genco, Caroline. Global Network Analysis of Neisseria gonorrhoeae Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection. United States: N. p., 2020. Web. doi:10.1128/mSystems.00729-19.
McClure, Ryan S., Sunkavalli, Ashwini, Balzano, Phillip, Massari, Paola, Cho, Christine, Nauseef, William M., Apicella, Michael A., & Genco, Caroline. Global Network Analysis of Neisseria gonorrhoeae Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection. United States. doi:10.1128/mSystems.00729-19.
McClure, Ryan S., Sunkavalli, Ashwini, Balzano, Phillip, Massari, Paola, Cho, Christine, Nauseef, William M., Apicella, Michael A., and Genco, Caroline. Tue . "Global Network Analysis of Neisseria gonorrhoeae Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection". United States. doi:10.1128/mSystems.00729-19. https://www.osti.gov/servlets/purl/1600632.
@article{osti_1600632,
title = {Global Network Analysis of Neisseria gonorrhoeae Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection},
author = {McClure, Ryan S. and Sunkavalli, Ashwini and Balzano, Phillip and Massari, Paola and Cho, Christine and Nauseef, William M. and Apicella, Michael A. and Genco, Caroline},
abstractNote = {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.},
doi = {10.1128/mSystems.00729-19},
journal = {mSystems},
number = 1,
volume = 5,
place = {United States},
year = {2020},
month = {2}
}

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