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 CiaR/H two-component system is involved in regulating virulence and competence in Streptococcus pneumoniae. The system is known to regulate many genes, including that for high-temperature requirement A (HtrA). This gene has been implicated in the ability of the pneumococcus to colonize the nasopharynx of infant rats. We reported previously that deletion of the gene for HtrA made the pneumococcal strains much less virulent in mouse models, less able to grow at higher temperatures, and more sensitive to oxidative stress. In this report, we show that the growth phenotype as well as sensitivity to oxidative stress of ⌬ciaR mutant was very similar to that of a ⌬htrA mutant and that the expression of the HtrA protein was reduced in a ciaR-null mutant. Both the in vitro phenotype and the reduced virulence of ⌬ciaR mutant could be restored by increasing the expression of HtrA.Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. This gram-positive organism is a major cause of a variety of diseases such as pneumonia, bacteremia, meningitis, otitis media, and sinusitis in both adults and children all over the world (40,43). The nasopharynx is the major reservoir of pneumococci, from which they can spread to other sites such as bloodstream or lung tissues (44).Pathogenic bacteria encounter a number of environmental stresses during their life cycle such as temperature shifts, variations in osmolarity, changes in pH, and nutrient deprivation (45). The pneumococcus responds to these stresses, particularly heat stress, by mediating a cascade of events leading to the synthesis of a unique group of proteins called heat shock proteins (HSPs) (7). The production of these proteins represents a protective cellular response to cope with the stressinduced damage of proteins (26). HSPs are molecular chaperones or proteases that take part in protein quality control during normal growth and under stress-inducing conditions (6,12).Recent studies have demonstrated the role of bacterial twocomponent signal-transducing systems in mediating adaptive responses to environmental signals (30, 38). The pneumococcal CiaR/H two-component system consists of a sensor histidine kinase, CiaH, anchored in the cell membrane and a cytoplasmic response regulator, CiaR, which is a DNA-binding protein involved in the regulation of genes in response to environmental signals sensed by CiaH (15). This system was identified as 1 of 13 two-component signal-transducing systems in two genomic screens (24, 42). Pleotropic effects caused by cia mutations in the pneumococcus include sensitivity to cefotaxime, an ability to form protoplast, susceptibility to lysis by deoxycholate (11), and a tendency to early lysis (24). CiaH mutants also have transformation deficiency (8,11,16). In vivo, CiaR/H has been shown to contribute to colonization of the mouse lung (42) and the nasopharynx of infant rats (35) and to be involved in systemic infection in mice (27). Previous studies have shown that the CiaR/H regulon contains many genes, including the hig...

The ATP-dependent caseinolytic proteases (Clp) are fundamental for stress tolerance and virulence in many pathogenic bacteria. The role of ClpC in the autolysis and virulence of Streptococcus pneumoniae is controversial. In this study, we tested the role of ClpC in a number of S. pneumoniae strains and found that the contribution of ClpC to autolysis is strain dependent. ClpC is required for the release of autolysin A and pneumolysin in serotype 2 S. pneumoniae strain D39. In vivo, ClpC is required for the growth of the pneumococcus in the lungs and blood in a murine model of disease, but it does not affect the overall outcome of pneumococcal disease. We also report the requirement of ClpP for the growth at elevated temperature and virulence of serotype 4 strain TIGR4 and confirm its contribution to the thermotolerance, oxidative stress resistance, and virulence of D39.

Social media is becoming a major development in electronic commerce among a wide range of sectors, for example, education, government, health care, and business. In Saudi Arabia, a major movement toward social media has taken place, especially among small business entrepreneurs, due to its low cost and the powerful role it can play in globalization.The goal of this paper is to add to the theoretical knowledge base regarding the adoption of social media among Saudi small businesses, by applying the Unified Theory of Acceptance and Use of Technology (UTAUT) model to examine the influences of Saudi small businesses’ social media adoption. An empirical study was carried out using online survey research among 73 Saudi business entrepreneurs. The major findings of the paper are that Saudi small business entrepreneurs tend to use social media for the major constructs of performance expectancy, effort expectancy, social influence, and facilitating conditions. However, although the moderator of gender proved to be effective on the construct of effort expectancy, the effects of the moderators of age, gender, and experience on the other major constructs were not salient.It is believed that the findings will be useful for understanding adoption phenomena better, to help business entrepreneurs to make superior decisions based on them.

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