Pneumolysin: Pathogenesis and Therapeutic Target.

Andrew T Nishimoto,Elaine I Tuomanen,Jason W Rosch

doi:10.3389/fmicb.2020.01543

Andrew T Nishimoto, Elaine I Tuomanen + Show 1 more

Open Access

https://doi.org/10.3389/fmicb.2020.01543

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Abstract

Streptococcus pneumoniae is an opportunistic pathogen responsible for widespread illness and is a major global health issue for children, the elderly, and the immunocompromised population. Pneumolysin (PLY) is a cholesterol-dependent cytolysin (CDC) and key pneumococcal virulence factor involved in all phases of pneumococcal disease, including transmission, colonization, and infection. In this review we cover the biology and cytolytic function of PLY, its contribution to S. pneumoniae pathogenesis, and its known interactions and effects on the host with regard to tissue damage and immune response. Additionally, we review statins as a therapeutic option for CDC toxicity and PLY toxoid as a vaccine candidate in protein-based vaccines.

Highlights

Streptococcus pneumoniae is a commensal organism responsible for a wide array of disease and is the source of considerable morbidity and mortality
The observed interaction of PLY with the phagocytic receptor, mannose receptor C type 1 (MRC-1), which is highly expressed in dendritic cells compared to neutrophils or GM-CSF derived macrophages, suggests that this dose-dependent inhibition of inflammatory cytokines aids in allowing S. pneumoniae to establish intracellular residency within the dendritic cells (Subramanian et al, 2019)
The cholesterol-dependent cytolysin (CDC) PLY has multiple interactions with the host leading to extensive spread of disease, intense inflammation and abundant cell damage

Summary

Introduction

Streptococcus pneumoniae is a commensal organism responsible for a wide array of disease and is the source of considerable morbidity and mortality. PLY’s effects in the body are numerous and diverse – contributing to inflammation and bacterial penetration, causing direct damage to cells through pore-forming cytolytic activity, aiding bacterial escape through blocking complement activation, and being a key factor in host-to-host pneumococcal transmission (Berry et al, 1989b; Rayner et al, 1995; Berry and Paton, 2000; Alcantara et al, 2001; Rogers et al, 2003; Mitchell and Dalziel, 2014; Zafar et al, 2017).

Results

Conclusion