Modelling the in-host dynamics of Neisseria gonorrhoeae infection. Issue 1 (16th February 2019)

• Record Type: Journal Article
• Authors: Jayasundara, Pavithra; Regan, David G; Seib, Kate L; Jayasundara, Duleepa; Wood, James G
• Is Part Of: Pathogens and disease. Volume 77:Issue 1(2019)
• Publication Date: 2019-02-16
• Subjects: Neisseria gonorrhoeae -- dynamic model -- host–pathogen interaction -- urethral infection -- neutrophils -- epithelial cells; Medical microbiology -- Periodicals; Pathogenic microorganisms -- Periodicals; Communicable diseases -- Microbiology -- Periodicals; Communicable diseases -- Pathogenesis -- Periodicals; Host-parasite relationships -- Periodicals; Systems biology -- Periodicals; 616.904105
• DOI: 10.1093/femspd/ftz008
• Languages: English
• ISSNs: 2049-632X

Abstract

ABSTRACT: The bacterial species Neisseria gonorrhoeae (NG) has evolved to replicate effectively and exclusively in human epithelia, with its survival dependent on complex interactions between bacteria, host cells and antimicrobial agents. A better understanding of these interactions is needed to inform development of new approaches to gonorrhoea treatment and prevention but empirical studies have proven difficult, suggesting a role for mathematical modelling. Here, we describe an in-host model of progression of untreated male symptomatic urethral infection, including NG growth and interactions with epithelial cells and neutrophils, informed by in vivo and in vitro studies. The model reproduces key observations on bacterial load and clearance and we use multivariate sensitivity analysis to refine plausible ranges for model parameters. Model variants are also shown to describe mouse infection dynamics with altered parameter ranges that correspond to observed differences between human and mouse infection. Our results highlight the importance of NG internalisation, particularly within neutrophils, in sustaining infection in the human model, with ∼80% of the total NG population internalised from day 25 on. This new mechanistic model of in-host NG infection dynamics should also provide a platform for future studies relating to antimicrobial treatment and resistance and infection at other anatomical sites. Abstract : An in-host mathematical model of gonorrhoea transmission was developed that describes the interaction of bacteria with the host immune response and that replicates the experimentally observed course of infection.