PNNL

Abstract

Neisseria gonorrhoeae is a sexually transmitted mucosal pathogen responsible for nearly 80 million cases of gonorrhea across the globe each year. N. gonorrhoeae predominately infects the male and female genital tract, however, the clinical manifestation of disease in men and women often diverges, with women suffering from asymptomatic infections that can progress to pelvic inflammatory disease and men showing strong symptomatic response. To understand gender-based differences in infection we expand our first transcriptome study of the gonococcus during natural infection in the female genital tract to include transcriptome analysis from the male genital tract. In these samples from infected males, RNA sequencing analysis revealed enriched expression of gonococcal genes involved in pilin, oxidative stress and gene regulators. The gonococcal transcriptome of the male genital tract was then compared to that of the female genital tract. Nearly 14% of gonococcal genes were differentially regulated between male and female infections, with 9.4% exhibiting higher expression in males and 4.3% exhibiting higher expression in females. Specific gene categories that were regulated via infection include phage associated genes, which were significantly enriched during infection of the female genital tract, and genes involved in host interactions, which were significantly enriched in the male genital tract. Finally, we investigated phenotypic and genotypic antibiotic resistance patterns in male and female subjects in our study as a snapshot of emerging antibiotic resistance in China. Interestingly, strains isolated from male and female subjects exhibit comparable antibiotic resistant genotypes and phenotypes, however, RNA-seq analysis revealed higher expression of the Mtr efflux pump in males. Collectively, we demonstrate that gene expression of N. gonorrhoeae has distinct signatures in the male and female genital tract that dictate disease outcomes. The knowledge gained from these studies will illuminate gender specific disease mechanisms and contribute to the development of effective therapies, a crucial need as antibiotic resistant strains of N. gonorrhoeae emerge worldwide.