Rot and SaeRS Cooperate To Activate Expression of the Staphylococcal Superantigen-Like Exoproteins

Benson, Meredith A.; Lilo, Sarit; Nygaard, Tyler K.; Voyich, Jovanka M.; Torres, Victor J.

doi:10.1128/jb.00706-12

Cited by 61 publications

(59 citation statements)

References 57 publications

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“…The PCR amplicons were digested with XmaI and assembled into pCR2.1 (Invitrogen). For the pCR2.1 construct containing the pvl fragments, the vector was digested with XmaI and ligated with the aminoglycoside-3Љ-adenylyltransferase (aad) gene also digested with XmaI to create an aad insertion within the pvl gene, as we have done previously for the generation of other mutants (32). A PCR amplicon of the joined DNA fragments was recombined into pKOR1, resulting in the pKOR-1⌬lukAB and pKOR-1⌬pvl:: spec plasmids.…”

Section: Methodsmentioning

confidence: 99%

“…Select LAC strains were transformed with pOS1-P sarA -sodRBS-sgfp, a plasmid that constitutively and robustly produces superfolded green fluorescent protein (GFP) from the sarA promoter using the superoxide dismutase (sod) ribosomal binding site (RBS) (see Table 3) (32). These strains were cultured with RPMIϩCAS supplemented with chloramphenicol at a final concentration of 10 g/ml.…”

Section: Methodsmentioning

confidence: 99%

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Staphylococcus aureus Elaborates Leukocidin AB To Mediate Escape from within Human Neutrophils

et al. 2013

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bMethicillin-resistant Staphylococcus aureus (MRSA) strains of the pulsed-field type USA300 are primarily responsible for the current community-associated epidemic of MRSA infections in the United States. The success of USA300 is partly attributed to the ability of the pathogen to avoid destruction by human neutrophils (polymorphonuclear leukocytes [PMNs]), which are crucial to the host immune response to S. aureus infection. In this work, we investigated the contribution of bicomponent poreforming toxins to the ability of USA300 to withstand attack from primary human PMNs. We demonstrate that in vitro growth conditions influence the expression, production, and availability of leukotoxins by USA300, which in turn impact the cytotoxic potential of this clone toward PMNs. Interestingly, we also found that upon exposure to PMNs, USA300 preferentially activates the promoter of the lukAB operon, which encodes the recently identified leukocidin AB (LukAB). LukAB elaborated by extracellular S. aureus forms pores in the plasma membrane of PMNs, leading to PMN lysis, highlighting a contribution of LukAB to USA300 virulence. We now show that LukAB also facilitates the escape of bacteria engulfed within PMNs, in turn enabling the replication and outgrowth of S. aureus. Together, these results suggest that upon encountering PMNs S. aureus induces the production of LukAB, which serves as an extra-and intracellular weapon to protect the bacterium from destruction by human PMNs.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Staphylococcus aureus Elaborates Leukocidin AB To Mediate Escape from within Human Neutrophils

et al. 2013

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“…FACS-based phagocytosis assays were performed using whole human blood and bacterial strains constitutively expressing GFP, as described by us previously (Kolar et al, 2013). The GFP-expressing plasmid pOS1sGFP : : P sarA (Benson et al, 2012) was transduced into the ctpA 2 mutant using bacteriophage W11 to create strain LNS1893. The number of GFP-positive granulocytes and macrophages was determined following 30 min of incubation of bacteria in human blood.…”

Section: Methodsmentioning

confidence: 99%

The lone S41 family C-terminal processing protease in Staphylococcus aureus is localized to the cell wall and contributes to virulence

et al. 2014

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Staphylococcus aureus is a versatile pathogen of humans and a continued public health concern due to the rise and spread of multidrug-resistant strains. As part of an ongoing investigation into the pathogenic mechanisms of this organism we previously demonstrated that an intracellular Nterminal processing protease is required for S. aureus virulence. Following on from this, here we examine the role of CtpA, the lone C-terminal processing protease of S. aureus. CtpA, a member of the S41 family, is a serine protease whose homologues in Gram-negative bacteria have been implicated in a range of biological functions, including pathogenesis. We demonstrate that S. aureus CtpA is localized to the bacterial cell wall and expression of the ctpA gene is maximal upon exposure to conditions encountered during infection. Disruption of the ctpA gene leads to decreased heat tolerance and increased sensitivity when exposed to components of the host immune system. Finally we demonstrate that the ctpA " mutant strain is attenuated for virulence in a murine model of infection. Our results represent the first characterization of a C-terminal processing protease in a pathogenic Gram-positive bacterium and show that it plays a critical role during infection.

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“…7) (309, 315). SaeRS is a two-component system that responds to host environmental cues, including PMNs, to upregulate the expression of a diverse repertoire of S. aureus secreted proteins, many of which are major virulence factors (304,309,310,(316)(317)(318)(319)(320)(321). SaeR binds to a consensus sequence within virulence factor promoters to induce gene expression (309,321).…”

Section: Regulation At the Transcriptional Levelmentioning

confidence: 99%

The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus

Alonzo

Torres

2014

Microbiol Mol Biol Rev

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SUMMARY The ability to produce water-soluble proteins with the capacity to oligomerize and form pores within cellular lipid bilayers is a trait conserved among nearly all forms of life, including humans, single-celled eukaryotes, and numerous bacterial species. In bacteria, some of the most notable pore-forming molecules are protein toxins that interact with mammalian cell membranes to promote lysis, deliver effectors, and modulate cellular homeostasis. Of the bacterial species capable of producing pore-forming toxic molecules, the Gram-positive pathogen Staphylococcus aureus is one of the most notorious. S. aureus can produce seven different pore-forming protein toxins, all of which are believed to play a unique role in promoting the ability of the organism to cause disease in humans and other mammals. The most diverse of these pore-forming toxins, in terms of both functional activity and global representation within S. aureus clinical isolates, are the bicomponent leucocidins. From the first description of their activity on host immune cells over 100 years ago to the detailed investigations of their biochemical function today, the leucocidins remain at the forefront of S. aureus pathogenesis research initiatives. Study of their mode of action is of immediate interest in the realm of therapeutic agent design as well as for studies of bacterial pathogenesis. This review provides an updated perspective on our understanding of the S. aureus leucocidins and their function, specificity, and potential as therapeutic targets.

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Rot and SaeRS Cooperate To Activate Expression of the Staphylococcal Superantigen-Like Exoproteins

Cited by 61 publications

References 57 publications

Staphylococcus aureus Elaborates Leukocidin AB To Mediate Escape from within Human Neutrophils

Staphylococcus aureus Elaborates Leukocidin AB To Mediate Escape from within Human Neutrophils

The lone S41 family C-terminal processing protease in Staphylococcus aureus is localized to the cell wall and contributes to virulence

The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus

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