Temporal Expression of Adhesion Factors and Activity of Global Regulators during Establishment ofStaphylococcus aureusNasal Colonization

Abstract

The human pathogen Staphylococcus aureus successfully colonizes its primary reservoir, the nasal cavity, most likely by regulatory adaptation to the nose environment. Cotton rats represent an excellent model for the study of bacterial gene expression in the initial phases of colonization. To gain insight into the expression profile necessary for the establishment of colonization, we performed direct transcript analysis by quantitative real-time reverse-transcription polymerase chain reaction on cotton rat noses removed from euthanized animals on days 1, 4, or 10 after instillation of 2 human S. aureus nose isolates. Global virulence regulators (agr, sae) were not active in this early phase, but the essential 2-component regulatory system WalKR seems to play an important role. Accordingly, an elevated expression of walKR target genes (sak, sceD) could be detected. In agreement with previous studies that demonstrated the essential role played by wall teichoic acid (WTA) polymers in nasal colonization, we detected a strongly increased expression of WTA-biosynthetic genes. The expression profile switched to production of the adhesive proteins ClfB and IsdA at later stages of the colonization process. These data underscore the temporal differences in the roles of WTA and surface proteins in nasal colonization, and they provide the first evidence for a regulation of WTA biosynthesis in vivo.

Proteomic and Transcriptomic Profiling of Staphylococcus aureus Surface LPXTG-proteins: Correlation with agr Genotypes and Adherence Phenotypes

“…Although this is possible at the level of mRNA (11,29,31), its equivalent at the protein level is as yet less developed (27)(28)(29). Individual proteins can be quantitatively evaluated by Western blotting or in situ hybridization.…”

“…Although the physiological role of SasD is as yet unclear, SasH (recently renamed AdsA (59)) is a cell wall associated adenosine synthase that converts adenosine-monophosphate into adenosine, a strong immunomodulator helping staphylococci to escape phagocyteinduced killing. Hence, SasH (or AdsA) could well be coregulated with the siderophore locus isd, which expression is induced in experimental S. aureus nasal colonization (11). In this setting, expression of isd could be required for survival in the low-iron mucosal environment, while SasH could be required to damper host defenses and promote bacterial persistence.…”

“…MSCRAMMs encompass several surface components including proteins, teichoic acids, lipoteichoic acids, and maybe polysaccharidic capsules, which have been implicated in tissue colonization and disease to various extents (5,10,11). Important surface proteins include polypeptides covalently attached to the peptidoglycan via a conserved anchoring mechanism.…”

Sialic Acid Catabolism in Staphylococcus aureus

“…While the pathogenic roles of many S. aureus secreted factors and surface proteins have been extensively studied, the physiology of this commensal in the colonization state and other host environments has received only limited attention (12,13). Sialic acid (N-acetylneuraminic acid [Neu5Ac]) is one example of a bioavailable energy source present in many host niches (14).…”

Expression of Virulence Factors by Staphylococcus aureus Grown in Serum

“…However, when S. aureus infects a host, the circumstances around bacterial cells are quite different from those in a medium, with the expression pattern of virulence factors in the host suggested to be quite different from that in culture media. Several investigations using animal models have characterized the regulation of virulence factor expression in vivo (4,5,24,28). However, from the findings of in vivo experiments, it is considered that many factors, including cellular immune factors and nutrient conditions, affect the expression of virulence factors, suggesting that the mechanisms of regulation of virulence factors in vivo are very complicated.…”