PNNL

Abstract

Neisseria gonorrhoeae is a Gram-negative diplococcus that is responsible for the sexually transmitted infection gonorrhea, a high morbidity disease both in the United States and worldwide. Over the last 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 several N. gonorrhoeae transcriptomic data sets that have recently been generated to infer the first global gene co-expression network of this pathogen. These included data sets obtained from N. gonorrhoeae grown under a variety of in vitro growth conditions including infection of human PMNs, from the examination of bacterial mutants and from natural human mucosal infection in men and women. 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 significant overlap in the response of N. gonorrhoeae to infection of the male genital tract and exposure to hydrogen peroxide stress in vitro. Network analysis also identified new targets of the gonococcal global regulatory protein Fur. Finally, examination of the network neighborhood of uncharacterized proteins allowed us to assign putative functions to several hypothetical proteins, including those responding to infection. Collectively, the characterization of the first gene co-expression network for N. gonorrhoeae described here has revealed new regulatory pathways, functions for uncharacterized hypothetical proteins and shown how processes critical to gonococcal infection in both men and women are linked to each other. 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.