Proteolytic Cleavage Inactivates the Staphylococcus aureus Lipoteichoic Acid Synthase

Wörmann, Mirka E.; Reichmann, Nathalie T.; Malone, Cheryl L.; Horswill, Alexander R.; Gründling, Angelika

doi:10.1128/jb.00369-11

Cited by 92 publications

(105 citation statements)

References 47 publications

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“…LtaS is a polyglycerol phosphate synthase involved in the synthesis of lipoteichoic acid, which is a component of the S. aureus envelope (33,34). It was recently demonstrated that SPase processes LtaS in S. aureus (115), which our results confirm, and along with our previous demonstration that SPase processes LtaS in S. epidermidis (82) suggests that SPase-mediated cleavage of LtaS is general and possibly physiologically significant. OatA is an O-acetyltransferase and an integral membrane protein that confers the high level of resistance to lysozyme observed in the staphylococci by O-acylating peptidoglycan muramic acid (13).…”

Section: Discussionsupporting

confidence: 81%

Type I Signal Peptidase and Protein Secretion in Staphylococcus aureus

Schallenberger¹,

Niessen²,

Shao³

et al. 2012

Journal of Bacteriology

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Section: Discussionsupporting

confidence: 81%

Type I Signal Peptidase and Protein Secretion in Staphylococcus aureus

Schallenberger¹,

Niessen²,

Shao³

et al. 2012

Journal of Bacteriology

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“…1A and B). This processing site has been confirmed for LtaS SA (39,44), and a similar processing is observed for the LtaS enzymes of B. anthracis (see below).…”

Section: Resultsmentioning

confidence: 59%

Synthesis of Lipoteichoic Acids in Bacillus anthracis

et al. 2012

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bLipoteichoic acid (LTA), a glycerol phosphate polymer, is a component of the envelope of Gram-positive bacteria that has hitherto not been identified in Bacillus anthracis, the causative agent of anthrax. LTA synthesis in Staphylococcus aureus and other microbes is catalyzed by the product of the ltaS gene, a membrane protein that polymerizes polyglycerol phosphate from phosphatidyl glycerol. Here we identified four ltaS homologues, designated ltaS1 to -4, in the genome of Bacillus anthracis. Polyglycerol phosphate-specific monoclonal antibodies were used to detect LTA in the envelope of B. anthracis strain Sterne (pXO1؊ ) vegetative forms. B. anthracis mutants lacking ltaS1, ltaS2, ltaS3, or ltaS4 did not display defects in growth or LTA synthesis. In contrast, B. anthracis strains lacking both ltaS1 and ltaS2 were unable to synthesize LTA and exhibited reduced viability, altered envelope morphology, aberrant separation of vegetative forms, and decreased sporulation efficiency. Expression of ltaS1 or ltaS2 alone in B. anthracis as well as in other microbes was sufficient for polyglycerol phosphate synthesis. Thus, similar to S. aureus, B. anthracis employs LtaS enzymes to synthesize LTA, an envelope component that promotes bacterial growth and cell division.

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“…Bursa aurealis transposon mutants from the Nebraska Library were obtained from the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA). The LAC ⌬aur ⌬sspAB ⌬scpA ⌬spl::Er (protease-null) mutant was provided by Lindsey Shaw (University of South Florida, Tampa, FL) (35). The LAC and COL sarA::Km r mutants were generated by 11-mediated transduction from a previously constructed mutant (36).…”

Section: Methodsmentioning

confidence: 99%

Regulatory Requirements for Staphylococcus aureus Nitric Oxide Resistance

et al. 2016

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The ability of Staphylococcus aureus to resist host innate immunity augments the severity and pervasiveness of its pathogenesis. Nitric oxide (NO˙) is an innate immune radical that is critical for the efficient clearance of a wide range of microbial pathogens. Exposure of microbes to NO˙typically results in growth inhibition and induction of stress regulons. S. aureus, however, induces a metabolic state in response to NO˙that allows for continued replication and precludes stress regulon induction. The regulatory factors mediating this distinctive response remain largely undefined. Here, we employ a targeted transposon screen and transcriptomics to identify and characterize five regulons essential for NO˙resistance in S. aureus: three virulence regulons not formerly associated with NO˙resistance, SarA, CodY, and Rot, as well as two regulons with established roles, Fur and SrrAB. We provide new insights into the contributions of Fur and SrrAB during NO˙stress and show that the S. aureus ⌬sarA mutant, the most sensitive of the newly identified mutants, exhibits metabolic dysfunction and widespread transcriptional dysregulation following NO˙exposure. Altogether, our results broadly characterize the regulatory requirements for NO˙resistance in S. aureus and suggest an intriguing overlap between the regulation of NO˙resistance and virulence in this well-adapted human pathogen. IMPORTANCEThe prolific human pathogen Staphylococcus aureus is uniquely capable of resisting the antimicrobial radical nitric oxide (NO˙), a crucial component of the innate immune response. However, a complete understanding of how S. aureus regulates an effective response to NO˙is lacking. Here, we implicate three central virulence regulators, SarA, CodY, and Rot, as major players in the S. aureus NO˙response. Additionally, we elaborate on the contribution of two regulators, SrrAB and Fur, already known to play a crucial role in S. aureus NO˙resistance. Our study sheds light on a unique facet of S. aureus pathogenicity and demonstrates that the transcriptional response of S. aureus to NO˙is highly pleiotropic and intrinsically tied to metabolism and virulence regulation. The versatile Gram-positive pathogen Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs) in the United States but can also cause more severe illnesses, including pneumonia, osteomyelitis, endocarditis, and bacteremia (1-5). The ability of S. aureus to infect virtually every tissue of the body can be partially attributed to its extensive capacity for subverting host immunity. One unique defense of S. aureus against the immune system is resistance to nitric oxide (NO˙), a membrane-permeable radical and broad-spectrum innate immune effector required for the clearance of bacterial, viral, and fungal pathogens (6). The ability of S. aureus to continue growth in the presence of NO˙at concentrations that are inhibitory to other bacteria, including closely related staphylococci, contributes to its invasiveness and pathogenic success. For example...

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Proteolytic Cleavage Inactivates the Staphylococcus aureus Lipoteichoic Acid Synthase

Cited by 92 publications

References 47 publications

Type I Signal Peptidase and Protein Secretion in Staphylococcus aureus

Type I Signal Peptidase and Protein Secretion in Staphylococcus aureus

Synthesis of Lipoteichoic Acids in Bacillus anthracis

Regulatory Requirements for Staphylococcus aureus Nitric Oxide Resistance

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