The saePQRS system of Staphylococcus aureus controls the expression of major virulence factors and encodes a histidine kinase (SaeS), a response regulator (SaeR), a membrane protein (SaeQ), and a lipoprotein (SaeP). The widely used strain Newman is characterized by a single amino acid change in the sensory domain of SaeS (Pro18 in strain Newman [SaeS P ], compared with Leu18 in other strains [SaeS L ]). SaeS P determines activation of the class I sae target genes (coa, fnbA, eap, sib, efb, fib, sae), which are highly expressed in strain Newman. In contrast, class II target genes (hla, hlb, cap) are not sensitive to the SaeS polymorphism. The SaeS L allele (saeS L ) is dominant over the SaeS P allele, as shown by single-copy integration of saePQRS L in strain Newman, which results in severe repression of class I target genes. The differential effect on target gene expression is explained by different requirements for SaeR phosphorylation. From an analysis of saeS deletion strains and strains with mutated SaeR phosphorylation sites, we concluded that a high level of SaeR phosphorylation is required for activation of class I target genes. However, a low level of SaeR phosphorylation, which can occur independent of SaeS, is sufficient to activate class II target genes. Using inducible saeRS constructs, we showed that the expression of both types of target genes is independent of the saeRS dosage and that the typical growth phase-dependent gene expression pattern is not driven by SaeRS.The human pathogen Staphylococcus aureus can cause a wide range of diseases. The versatility of this organism is due to its capacity to produce accessory molecules that mediate specific interactions with the host cells. Most of these factors are tightly regulated by global regulatory loci, such as agr, rot, sigB, and sae, which act as an interactive regulatory network to ensure that there is coordinated temporal expression of virulence factors. Within the network, the sae system appears to be a central downstream regulator. Mutations in sae do not affect the transcription of agr, sigB, sarA, or rot (18,22,35). However, at least in some strains, agr activates sae transcription, while sigB and rot repress sae transcription (17,19,21,35,44 (18,33,36,44,46,48,52).The sae locus consists of four open reading frames (ORFs), and the products of two of these ORFs (saeR and saeS) show strong sequence homology to bacterial two-component regulators composed of a histidine kinase (HK), SaeS, and a response regulator (RR), SaeR. Two additional ORFs, ORF3 (saeQ) and ORF4 (saeP), which are located upstream of saeRS, are likely to be important for the function of the sae operon (1,17,48). saeP encodes a putative lipoprotein, and saeQ encodes a membrane protein with four membrane-spanning stretches. Four overlapping sae-specific transcripts (T1 to T4) have been detected; the T1 message (3.1 kb) initiates upstream of saeP, T2 (2.4 kb) initiates upstream of saeQ, and T3 (2.0 kb) initiates upstream of saeR. T4 (0.7 kb) represents a monocistronic mRNA encom...

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To achieve a complete remission of cutaneous and ocular rosacea, a long-term anti-inflammatory treatment of at least 6 months is necessary. The relapse rates seem to be lower than in adults especially in the patients treated with erythromycin.

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