Transcriptional Profiling of XdrA, a New Regulator ofspaTranscription inStaphylococcus aureus

Abstract

Transcription of spa, encoding the virulence factor protein A in Staphylococcus aureus, is tightly controlled by a complex regulatory network, ensuring its temporal expression over growth and at appropriate stages of the infection process. Transcriptomic profiling of XdrA, a DNA-binding protein that is conserved in all S. aureus genomes and shares similarity with the XRE family of helix-turn-helix, antitoxin-like proteins, revealed it to be a previously unidentified activator of spa transcription. To assess how XdrA fits into the complex web of spa regulation, a series of regulatory mutants were constructed; consisting of single, double, triple, and quadruple mutants lacking XdrA and/or the three key regulators previously shown to influence spa transcription directly (SarS, SarA, and RNAIII). A series of lacZ reporter gene fusions containing nested deletions of the spa promoter identified regions influenced by XdrA and the other three regulators. XdrA had almost as strong an activating effect on spa as SarS and acted on the same spa operator regions as SarS, or closely overlapping regions. All data from microarrays, Northern and Western blot analyses, and reporter gene fusion experiments indicated that XdrA is a major activator of spa expression that appears to act directly on the spa promoter and not through previously characterized regulators.

Genome-wide screen for genes involved in eDNA release during biofilm formation by Staphylococcus aureus

“…We observed significant changes in transcript levels, both increases and decreases, for more than 100 genes when comparing the ΔxdrA mutant to wild-type cells. Consistent with previous reports, we saw a reduction in spa transcript levels in ΔxdrA mutant cells during exponential growth (25), and during biofilm formation and during growth at low pH. Only one other gene (the small RNA transcribed from a region downstream of SAOUHSC_00377) was similarly affected in all conditions tested.…”

Identification of a cis‐acting element in nitrogen fixation genes recognized by CnfR in the nonheterocystous nitrogen‐fixing cyanobacterium Leptolyngbya boryana

“…The XRE-type regulatory domain is the second-most frequent regulator family in bacteria. This domain is often fused with other various domains to allow highly diverged physiological functions, such as phage repression (McDonnell and McConnell, 1994), modulation of restriction-modification systems (McGeehan et al, 2008), swarming motility and biofilm formation (Wang et al, 2014), virulence (McCallum et al, 2010) and anaerobic catabolism (Barrag an et al, 2005). A globular structure formed by five ahelices is a common feature of the XRE-type DNA binding domain (Xu et al, 2012).…”

Mutation in the C-Di-AMP Cyclase dacA Affects Fitness and Resistance of Methicillin Resistant Staphylococcus aureus

“…Examples of fem/aux factors linked to the cell envelope include cell wall biosynthesis enzymes like GlmM [11], MurE [12], MurF [13], FemABX [14], PBP2 [15], PBP4 [16]; and wall teichoic acid biosynthesis enzymes including TagO/TarO [17], the dlt operon [18] and the wall teichoic acid ligase MsrR [19], [20]. Fem/aux factors indirectly connected or with no obvious connection to the cell envelope include regulators like SigB [21], SpoVG [22], agr [23], SarA [23], XdrA [24], CcpA [25], SecDF [26] or two component systems like VraSR [27], [28].…”