Current concepts in host–microbe interaction leading to pneumococcal pneumonia

Abstract

Purpose of review Infection with Streptococcus pneumoniae (pneumococcus) results in colonization, which can lead to local or invasive disease, of which pneumonia is the most common manifestation. Despite the availability of pneumococcal vaccines, pneumococcal pneumonia is the leading cause of community and in-hospital pneumonia in the United States and globally. This article discusses new insights into the pathogenesis of pneumococcal disease. Recent findings The host-microbe interactions that determine whether pneumococcal colonization will result in clearance or invasive disease are highly complex. This paper focuses on new information in three areas that bear on the pathogenesis of pneumococcal disease: 1) factors that govern colonization, the prelude to invasive disease, including effects on colonization and invasion of capsular serotype, pneumolysin, surface proteins that regulate complement deposition, biofilm formation and agglutination; 2) the effect of co-infection with other bacteria and viruses on pneumococcal growth and virulence, including the synergistic effect of influenza; and 3) the contribution of the host inflammatory response to the pathogenesis of pneumococcal pneumonia, including the effects of pattern recognition molecules, cells that enhance and modulate inflammation, and therapies that modulate inflammation, such as statins. Summary Recent research on pneumococcal pathogenesis reveals new mechanisms by which microbial factors govern the ability of pneumococcus to progress from the state of colonization to disease and host inflammatory responses contribute to the development of pneumonia. These mechanisms suggest that therapies which modulate the inflammatory response could hold promise for ameliorating damage due to the inflammatory response in pneumococcal disease.

Minimal Peptidoglycan (PG) Turnover in Wild-Type and PG Hydrolase and Cell Division Mutants of Streptococcus pneumoniae D39 Growing Planktonically and in Host-Relevant Biofilms

“…pneumoniae is a human commensal bacterium that colonizes the nasopharynx as a biofilm and that can become an opportunistic pathogen in individuals recovering from influenza or with compromised immune systems, causing a number of serious respiratory and invasive diseases, such as pneumonia (26)(27)(28). Alterations in PG biosynthesis have strong effects on the efficiency of pneumococcal colonization and infection.…”

Pneumococcal Vaccination Strategies. An Update and Perspective

“…Studies in innate immunity have shed light on the importance of complement, surfactant proteins, antimicrobial peptides, and several classes of pattern recognition receptors that recognize pathogenassociated molecular patterns and bacterial virulence factors on the pneumococci, which include the antiphagocytic polysaccharide capsule (27,32,(34)(35)(36)(37)(38)(39). Other important bacterial determinants include the pili, various adhesions, and toxins, including pneumolysin and autolysin (40).…”

Review: Current and new generation pneumococcal vaccines

“…121,122 A Ply export mechanism has also been described, which may account for the presence of the toxin on the cell wall of the 20 Ply, which is produced by all clinical isolates of the pneumococcus, is also considered to be a priority candidate antigen for inclusion in pneumococcal vaccines. 80 These various pneumococcal protein adhesin and invasin vaccine candidates are summarised in Table 1.…”