Role of HtrA in the Virulence and Competence of Streptococcus pneumoniae

Abstract

HtrA is a major virulence factor of Streptococcus pneumoniae (the pneumococcus). Deletion of the gene for HtrA from strain D39 of the pneumococcus completely abolished its virulence in mouse models of pneumonia and bacteremia, while the virulence of a second strain (TIGR4) was dramatically reduced. HtrA-negative mutants induced much less inflammation in the lungs during pneumonia than the wild type. HtrA is involved in the ability of the pneumococcus to grow at high temperatures, to resist oxidative stress, and to undergo genetic transformation. The expression and cellular location of several known virulence factors of the pneumococcus were not affected by the lack of HtrA.

The HtrA Protease from Streptococcus pneumoniae Digests Both Denatured Proteins and the Competence-stimulating Peptide

“…This activity against unfolded proteins resembles what has been characterized for DegP but, when combined with activity against CSP, generates the potential for cell signaling that is responsive to protein folding stress. The ability of HtrA to digest denatured proteins is also consistent with previous reports that pneumococcal htrA mutants have a reduced ability to tolerate thermal or oxidative stresses (45) and show a greater reduction in growth rate with subinhibitory concentrations of the antibiotic streptomycin, which causes ribosomal errors (8).…”

HtrA in Porphyromonas gingivalis can regulate growth and gingipain activity under stressful environmental conditions

“…Consistent with reports of other organisms (Ibrahim et al, 2004;Mutunga et al, 2004;Wonderling et al, 2004), our data also suggest that the htrA-defective mutant is more susceptible to hydrogen peroxide than the wild-type. This was also observed in a similar study by L. Yuan & A. ProgulskeFox (unpublished).…”

Alveolar macrophages in pulmonary host defence – the unrecognized role of apoptosis as a mechanism of intracellular bacterial killing

“…S. pneumoniae has evolved to cope with the resultant oxidative stress in several ways; sodA encodes the manganese superoxide dismutase (MnSOD) that removes superoxide, the NADH oxidase encoded by nox removes O2 to H2O, preventing its conversion to superoxide, SpxB enables acetyl phosphate to be converted to adenosine triphosphate (ATP), preventing ATP depletion during oxidative stress, psaA encodes a manganese permease and psaD a putative glutathione reductase, which together alter redox status and limit hydrogen peroxide production via SpxB, while AdhC is an alcohol dehydrogenase that generates the reduced glutathione required for PsaD [55][56][57][58][59][60]. Other factors contributing to resistance to oxidative stress include the heat shock-induced protease HtrA, a putative alkylhydroperoxidase AhpD, the ClpP protease, a putative transcriptional regulator Rgg and a putative thioredoxin-like protein TlpA [61][62][63][64][65]. Although arising primarily as a mechanism by which S. pneumoniae can withstand the ROS generated by their own metabolism, the range of strategies employed to withstand oxidative stress suggest that the bacteria should be relatively more resistant to the ROS, produced by macrophages after ingestion of bacteria, than bacteria that lack these adaptations.…”