In or out: Phagosomal escape of<i>Staphylococcus aureus</i>

Moldovan, Adriana; Fraunholz, Martin

doi:10.1111/cmi.12997

Cited by 73 publications

(81 citation statements)

References 119 publications

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“…12, 13-16]. Invasion of tissue cells is facilitated by numerous different bacterial adhesins and followed by escape from the bacteria-containing vacuole and cytosolic replication [reviewed in 17, 18, 19]. In professional phagocytes, intracellular S. aureus is able to resist the antimicrobial attack by the host cell and replication occurs within phagosomes.…”

Section: Introductionmentioning

confidence: 99%

IntracellularStaphylococcus aureusemploys the cysteine protease staphopain A to induce host cell death in epithelial cells

Stelzner

Hertlein

Sroka

et al. 2020

Preprint

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Staphylococcus aureus is a major human pathogen, which can invade and survive in non-professional and professional phagocytes. Intracellularity is thought to contribute to pathogenicity and persistence of the bacterium. Upon internalization by epithelial cells, cytotoxic S. aureus strains can escape from the phagosome, replicate in the cytosol and induce host cell death. Here, we identified a staphylococcal cysteine protease to induce cell death by intracellular S. aureus after translocation into the host cell cytoplasm. We demonstrated that loss of staphopain A function leads to delayed onset of host cell death and prolonged intracellular replication of S. aureus in epithelial cells. Overexpression of staphopain A in a non-cytotoxic strain facilitated intracellular killing of the host cell even in the absence of detectable intracellular replication. Moreover, staphopain A contributed to efficient colonization of the lung in a mouse pneumonia model. Our study suggests that staphopain A is utilized by S. aureus to mediate escape from the host cell and thus contributes to tissue destruction and dissemination of infection. Author Summary Staphylococcus aureus is a well-known antibiotic-resistant pathogen that emerges in hospital and community settings and can cause a variety of diseases ranging from skin abscesses to lung inflammation and blood poisoning. The bacterium asymptomatically colonizes the upper respiratory tract and skin of about one third of the human population and takes advantage of opportune conditions, like immunodeficiency or breached barriers, to cause infection. Although S. aureus is not regarded as a professional intracellular bacterium, it can be internalized by human cells and subsequently exit the host cells by induction of cell death, which is considered to cause tissue destruction and spread of infection. The bacterial virulence factors and underlying molecular mechanisms involved in the intracellular lifestyle of S. aureus remain largely unknown. We identified a bacterial cysteine protease to contribute to host cell death mediated by intracellular S. aureus. Staphopain A induced killing of the host cell after translocation of the pathogen into the cell cytosol, while bacterial proliferation was not required. Further, the protease enhanced survival of the pathogen during lung infection. These findings reveal a novel, intracellular role for the bacterial protease staphopain A.

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Section: Introductionmentioning

confidence: 99%

IntracellularStaphylococcus aureusemploys the cysteine protease staphopain A to induce host cell death in epithelial cells

Stelzner

Hertlein

Sroka

et al. 2020

Preprint

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“…macrophages and neutrophils) and nonprofessional (non-phagocytic) cells (e.g. osteoclasts and fibroblasts) (25). In vivo, the fraction of Staphylococcus aureus that persists intracellularly gains protection from further antibiotics to eventually escape and spread bacteria beyond the initial site of infection (26).…”

Section: _______________________________________mentioning

confidence: 99%

“…During Staphylococcus infection, bacteria internalize via phagocytosis to enter an endosomal compartment that is initially Rab5and subsequently Rab7-positive (27,28). Although still controversial, evidence indicates that Staphylococcus utilize a number of virulence systems to prevent full activation of the phagolysosomal degradative compartment to enable survival (25).…”

Section: Whilementioning

confidence: 99%

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Inhibition of the ULK1 protein complex suppresses Staphylococcus-induced autophagy and cell death

Radhi

Davidson

Scott

et al. 2019

Journal of Biological Chemistry

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“…Interestingly, SCVs have the capacity to infect and survive within a wide range of eukaryotic host cells both in vitro and in vivo (9, 10, 17-24), possibly contributing to the long-term persistence of S. aureus in the airways of patients with chronic lung diseases despite appropriate antimicrobial treatments (25, 26). Intracellular S. aureus have evolved different strategies to evade host defence machineries and silently persist within their intracellular location (27, 28).…”

Section: Introductionmentioning

confidence: 99%

Transketolase is involved in the control of Sigma B during chronic infection byStaphylococcus aureus

Tan

Ramond

Jamet

et al. 2019

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In or out: Phagosomal escape ofStaphylococcus aureus

Cited by 73 publications

References 119 publications

IntracellularStaphylococcus aureusemploys the cysteine protease staphopain A to induce host cell death in epithelial cells

IntracellularStaphylococcus aureusemploys the cysteine protease staphopain A to induce host cell death in epithelial cells

Inhibition of the ULK1 protein complex suppresses Staphylococcus-induced autophagy and cell death

Transketolase is involved in the control of Sigma B during chronic infection byStaphylococcus aureus

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