A New Two-Component Regulatory System Involved in Adhesion, Autolysis, and Extracellular Proteolytic Activity of Staphylococcus aureus

Abstract

A transposition mutant of Staphylococcus aureus was selected from the parent strain MT23142, a derivative of strain 8325. The site of transposition was near the 5 terminus of the gene arlS. ArlS exhibits strong similarities with histidine protein kinases. Sequence analysis suggested that arlS forms an operon with upstream gene arlR. The predicted product of arlR is a member of the OmpR-PhoB family of response regulators. The arlS mutant formed a biofilm on a polystyrene surface unlike the parent strain and the complemented mutant. Biofilm formation was associated with increased primary adherence to polystyrene, whereas cellular adhesion was only slightly decreased. In addition, the arlS mutant exhibited increased autolysis and altered peptidoglycan hydrolase activity compared to the parental strain and to the complemented mutant. As it has been shown for coagulase-negative staphylococci that some autolysins are able to bind polymer surfaces, these data suggest that the two-component regulatory system ArlS-ArlR may control attachment to polymer surfaces by affecting secreted peptidoglycan hydrolase activity. Finally, the arlS mutant showed a dramatic decrease of extracellular proteolytic activity, including serine protease activity, in comparison to the wild-type strain and the complemented mutant, and cells grown in the presence of phenylmethylsulfonyl fluoride (a serine protease inhibitor) showed an increased autolysin activity. Since the locus arlR-arlS strikingly modifies extracellular proteolytic activity, this locus might also be involved in the virulence of S. aureus.

Genome-wide transcriptional profiling of the cell envelope stress response and the role of LisRK and CesRK in Listeria monocytogenes

“…Curiously, CesRK-like systems are absent in both S. aureus and B. subtilis, whereas in Enterococcus faecalis, the CesRKlike system CroRS has been shown to play a role in the intrinsic resistance to b-lactam antibiotics (Comenge et al, 2003;Hancock & Perego, 2004). In S. aureus, a LisRK-like system, ArlRS, has been shown to be involved in the control of autolysis, cell growth and virulence (Fournier et al, 2001;Fournier & Hooper, 2000;Liang et al, 2005); however in B. subtilis, LisRK-like systems are absent (Jordan et al, 2008). Collectively, these observations suggest that in L. monocytogenes, a regulatory network consisting of at least four TCSs is orchestrating the response to cell envelope stress.…”

Implication of the NorB Efflux Pump in the Adaptation of Staphylococcus aureus to Growth at Acid pH and in Resistance to Moxifloxacin

“…Although acid stress responses do not include increases in major virulence factors or biofilm formation, there were noteworthy changes in several global regulators that control the expression of virulence genes and drug efflux transporters (5), such as the SaeRS and ArlRS, two-component regulators, the Ser/Thr kinase PknB, and its phosphatase Stp1. These global regulators have been shown to be important in modulating virulence factor and drug transporter expression (9,11,22,23,26). Other regulators exhibit increased expression at pH 4.5, including the transcriptional regulator of the iron regulator Fur family (SACOL1541), the histidine kinases PhoP and KdpD, and the VraS protein of the cell wall stimulon response (10,14,16).…”

The arl locus positively regulates Staphylococcus aureus type 5 capsule via an mgrA-dependent pathway

“…However, some known regulatory genes involved in capsule regulation, such as agr or mgr, were not identified, suggesting that the library is biased to some degree. Among the genes identified, we chose to focus on arl since this locus has been shown to be an important regulator affecting the expression of several virulence factors in S. aureus, including autolysin and various toxins (Fournier & Hooper, 2000;, but how it regulates capsule has not been studied. Our results showed that arl positively controlled the production of capsule.…”

“…The arlRS system has been shown to be involved in regulation of several virulence genes in S. aureus (Fournier & Hooper, 2000;). The two genes form an operon, and mutations in each gene have been shown to result in the same phenotype .…”

“…In this study, we employed Tn551 mutagenesis to identify several putative regulatory loci that influenced CP5/ 8 production. We chose to focus on arl, a locus which has previously been shown to regulate autolysis and some secreted proteins (Fournier & Hooper, 2000;, and showed that the locus positively regulated CP5/8 expression at the transcriptional level mainly via an mgrAdependent pathway.…”