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Global Network Analysis of Neisseria gonorrhoeae Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection.
mSystems. 2020 Feb 04; 5(1)M

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.

Authors+Show Affiliations

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA.Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA. Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA. Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts, USA caroline.genco@tufts.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32019834

Citation

McClure, Ryan, et al. "Global Network Analysis of Neisseria Gonorrhoeae Identifies Coordination Between Pathways, Processes, and Regulators Expressed During Human Infection." MSystems, vol. 5, no. 1, 2020.
McClure R, Sunkavalli A, Balzano PM, et al. Global Network Analysis of Neisseria gonorrhoeae Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection. mSystems. 2020;5(1).
McClure, R., Sunkavalli, A., Balzano, P. M., Massari, P., Cho, C., Nauseef, W. M., Apicella, M. A., & Genco, C. A. (2020). Global Network Analysis of Neisseria gonorrhoeae Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection. MSystems, 5(1). https://doi.org/10.1128/mSystems.00729-19
McClure R, et al. Global Network Analysis of Neisseria Gonorrhoeae Identifies Coordination Between Pathways, Processes, and Regulators Expressed During Human Infection. mSystems. 2020 Feb 4;5(1) PubMed PMID: 32019834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Global Network Analysis of Neisseria gonorrhoeae Identifies Coordination between Pathways, Processes, and Regulators Expressed during Human Infection. AU - McClure,Ryan, AU - Sunkavalli,Ashwini, AU - Balzano,Phillip M, AU - Massari,Paola, AU - Cho,Christine, AU - Nauseef,William M, AU - Apicella,Michael A, AU - Genco,Caroline A, Y1 - 2020/02/04/ PY - 2020/2/6/entrez PY - 2020/2/6/pubmed PY - 2020/2/6/medline KW - Neisseria gonorrhoeae KW - RNA-seq KW - global regulatory networks KW - human infection KW - network analysis KW - regulatory proteins KW - transcriptomics JF - mSystems VL - 5 IS - 1 N2 - 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. SN - 2379-5077 UR - https://www.unboundmedicine.com/medline/citation/32019834/Global_Network_Analysis_of_Neisseria_gonorrhoeae_Identifies_Coordination_between_Pathways_Processes_and_Regulators_Expressed_during_Human_Infection_ L2 - https://doi.org/10.1128/mSystems.00729-19 DB - PRIME DP - Unbound Medicine ER -
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