Anatomical site-specific contributions of pneumococcal virulence determinants

Abstract

Streptococcus pneumoniae is an opportunistic pathogen globally associated with significant morbidity and mortality. It is capable of causing a wide range of diseases including sinusitis, conjunctivitis, otitis media, pneumonia, bacteraemia, sepsis, and meningitis. While its capsular polysaccharide is indispensible for invasive disease, and opsonising antibodies against the capsule are the basis for the current vaccines, a long history of biomedical research indicates that other components of this Gram-positive bacterium are also critical for virulence. Herein we review the contribution of pneumococcal virulence determinants to survival and persistence in the context of distinct anatomical sites. We discuss how these determinants allow the pneumococcus to evade mucociliary clearance during colonisation, establish lower respiratory tract infection, resist complement deposition and opsonophagocytosis in the bloodstream, and invade secondary tissues such as the central nervous system leading to meningitis. We do so in a manner that highlights both the critical role of the capsular polysaccharide and the accompanying and necessary protein determinants. Understanding the complex interplay between host and pathogen is necessary to find new ways to prevent pneumococcal infection. This review is an attempt to do so with consideration for the latest research findings.

Keywords: Host-pathogen interactions; Pathogenesis; Pneumococcus; Streptococcus pneumoniae; Virulence.

Fig. 1

Streptococcus pneumoniae virulence determinants and host immune responses associated with pneumococcal infection in an anatomical site-specific manner. S. pneumoniae virulence factors known to play a major role in pneumococcal colonisation and infection of the respiratory mucosa, systemic circulation, and the brain, are listed in the left panel with the respective site-specific anti-pneumococcal host responses displayed in the right panel. The role of host–pathogen molecular interaction in pneumococcal migration across the respiratory epithelial–endothelial barrier and the blood–brain barrier is also highlighted in anatomical context. PrtA, serine protease; PspA, pneumococcal surface protein A; AMPs, antimicrobial peptides; PdgA, N-acetylglucosamine deacetylase; Adr, O-acetyl transferase; IgA, immunoglobulin A; CbpA, choline binding protein A; ChoP, cell wall phosphorylcholine; PsrP, pneumococcal serine rich repeat protein; MSCRAMMs, microbial surface components recognising adhesive matrix molecules; PavA, pneumococcal adhesion and virulence A; PavB, pneumococcal adhesion and virulence B; CAZymes, carbohydrate-active enzymes; NanA, neuraminidase; BgaA, beta-galactosidase; StrH, beta-N-acetylgucosaminidase; Hyl, hyaluronate lysase; PhpA, histidine triad protein A; LytA, pneumococcal autolysin; Ply, pneumolysin; SpxB, pneumococcal pyruvate oxidase; EndA, endonuclease; sIgA, secretory IgA; CRP, C-Reactive protein; NETs, neutrophil extracellular traps; PAFR, platelet activating factor receptor; pIgR, polymeric immunoglobulin receptor; LR, laminin receptor