Streptococcus pneumoniaeAutolysis Prevents Phagocytosis and Production of Phagocyte-Activating Cytokines

Abstract

Streptococcus pneumoniae is a major pathogen in humans. The pathogenicity of this organism is related to its many virulence factors, the most important of which is the thick pneumococcal capsule that minimizes phagocytosis. Another virulence-associated trait is the tendency of this bacterium to undergo autolysis in stationary phase through activation of the cell wall-bound amidase LytA, which breaks down peptidoglycan. The exact function of autolysis in pneumococcal pathogenesis is, however, unclear. Here, we show the selective and specific inefficiency of wild-type S. pneumoniae for inducing production of phagocyte-activating cytokines in human peripheral blood mononuclear cells (PBMC). Indeed, clinical pneumococcal strains induced production of 30-fold less tumor necrosis factor (TNF), 15-fold less gamma interferon (IFN-␥), and only negligible amounts of interleukin-12 (IL-12) compared with other closely related Streptococcus species, whereas the levels of induction of IL-6, IL-8, and IL-10 production were similar. If pneumococcal LytA was inactivated by mutation or by culture in a medium containing excess choline, the pneumococci induced production of significantly more TNF, IFN-␥, and IL-12 in PBMC, whereas the production of IL-6, IL-8, and IL-10 was unaffected. Further, adding autolyzed pneumococci to intact bacteria inhibited production of TNF, IFN-␥, and IL-12 in a dose-dependent manner but did not inhibit production of IL-6, IL-8, and IL-10 in response to the intact bacteria. Fragments from autolyzed bacteria inhibited phagocytosis of intact bacteria and reduced the in vitro elimination of pneumococci from human blood. Our results suggest that fragments generated by autolysis of bacteria with reduced viability interfere with phagocyte-mediated elimination of live pneumococci.

Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia

“…During transformation, a small subpopulation of pneumococci are initially lysed [26] and the pneumococcal DNA is detected after infecting human lung specimens in vitro , which is accompanied by the increased secretion of inflammatory cytokines [31]. Additionally, the inhibition of autolysis can prevent phagocytosis and cytokine production [32]. However, Pep27 itself does not show any cytotoxicity to human erythrocytes [33].…”

Spermidine Biosynthesis and Transport Modulate Pneumococcal Autolysis

“…LytA may mediate lysis to release other virulence factors, such as pneumolysin (37), or release proteins involved in immune evasion or cell wall components that may modulate the host innate immune response (38). Another theory suggests that murein hydrolases are released to lyse neighboring noncompetent pneumococcal cells in a fratricidal manner, facilitating genetic exchange between naturally competent pneumococcal populations (39).…”

Desenvolvimento e avaliação da resposta imune humoral de uma vacina anti-pneumocócica conjugada: polissacarídeo capsular sorotipo 14 - proteína de superfície pneumocócica A.

“…A autolisina (N-acetil-muramoil-L-alanina amidase) é uma enzima ancorada à parede celular através de interações com resíduos de colina em moléculas de ácidos teicóico e lipoteicóico (KADIOGLU et al, 2008;MARTNER et al, 2009).…”

“…Esse processo de autólise mediado pela autolisina ocorre através da síntese e degradação do peptideoglicano da parede celular mostrando, então, o seu envolvimento na divisão celular do microrganismo (MARTNER et al, 2009;WHATMORE;DOWSON, 1999).…”

“…Sendo assim, a autolisina apresenta um papel direto na patogênese através da liberação de produtos de degradação da parede celular e de membrana, tais como fragmentos de peptideoglicano solúveis e ácido lipoteicóico que induzem a resposta inflamatória, assim como um papel indireto através da lise e liberação de fatores de virulência como a pneumolisina, que não é liberada ativamente da célula (MARTNER et al, 2009;WHATMORE;DOWSON, 1999).…”