Protective Role of Surfactant Protein D in Ocular Staphylococcus aureus Infection

Zhang, Zhiyong; Abdel-Razek, Osama; Hawgood, Samuel; Wang, Guirong

doi:10.1371/journal.pone.0138597

Cited by 22 publications

(29 citation statements)

References 54 publications

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“…Treatment with the cysteine protease inhibitor E-64d prior to infection led to a significant reduction in death of host cells infected with S. aureus (Fig 1A) thereby suggesting an involvement of cysteine proteases of either host or pathogen origin in the pathogen-induced host cell death. Inhibition of cysteine proteases by E-64 in a murine ocular infection model also resulted in reduced S. aureus virulence, as shown by reduced ocular injury and enhanced bacterial clearance [74]. We therefore tested insertional S. aureus mutants within either of the structural genes, scp A and ssp B, for cell death phenotypes.…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…The original SP-D KO mice (C57BL/6 background) were kindly provided by Dr. Hawgood (University of California, San Francisco) 55 and C57BL/6 WT mice were purchased from Jackson Laboratories (Bar Harbor, ME). The mice used for experiments of this study were bred and maintained in the animal core facility at SUNY Upstate Medical University.…”

Section: Methodsmentioning

confidence: 99%

Surfactant protein D attenuates acute lung and kidney injuries in pneumonia-induced sepsis through modulating apoptosis, inflammation and NF-κB signaling

Abdel-Razek

Shi

et al. 2018

Sci Rep

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Pneumonia and sepsis are major risk factors for acute kidney injury (AKI). Patients with pneumonia and AKI are at increased risk for morbidity and mortality. Surfactant protein D (SP-D) expressed in lung and kidney plays important roles in innate immunity. However, little is known about the role of organ-specific SP-D in the sepsis. The current study uses wild type (WT), SP-D knockout (KO), and humanized SP-D transgenic (hTG, lung-specific SP-D expression) mice to study organ-specific role of SP-D in pneumonia-induced sepsis. Analyses demonstrated differential lung and kidney injury among three-type mice infected with Pseudomonas aeruginosa. After infection, KO mice showed higher injurious scores in both lung and kidney, and decreased renal function than WT and hTG mice. hTG mice exhibited comparable lung injury but more severe kidney injury compared to WT mice. Increased renal tubular apoptosis, NF-κB activation and proinflammatory cytokines in the kidney of KO mice were found when compared with WT and hTG mice. Furthermore, in vitro primary proximal tubular epithelial cells from KO mice showed more apoptosis with higher level of activated caspase-3 than those from WT mice after LPS treatment. Collectively, SP-D attenuates AKI in the sepsis by modulating renal apoptosis, inflammation and NF-κB signaling.

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“…The SP-D KO mice were backcrossed at least 10 generations with C57BL/6 background mice 59 60 . All SP-D KO mice used in this study were bred in the animal core facility at SUNY Upstate Medical University 61 . Age-matched C57BL/6 WT mice were purchased from Jackson Laboratories (Bar Harbor, ME).…”

Section: Methodsmentioning

confidence: 99%

Innate Immune Molecule Surfactant Protein D Attenuates Sepsis-induced Acute Pancreatic Injury through Modulating Apoptosis and NF-κB-mediated Inflammation

Shi

Liu

et al. 2015

Sci Rep

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Sepsis causes multiple-organ dysfunction including pancreatic injury, thus resulting in high mortality. Innate immune molecule surfactant protein D (SP-D) plays a critical role in host defense and regulating inflammation of infectious diseases. In this study we investigated SP-D functions in the acute pancreatic injury (API) with C57BL/6 Wild-type (WT) and SP-D knockout (KO) mice in cecal ligation and puncture (CLP) model. Our results confirm SP-D expression in pancreatic islets and intercalated ducts and are the first to explore the role of pancreatic SP-D in sepsis. CLP decreased pancreatic SP-D levels and caused severe pancreatic injury with higher serum amylase 24 h after CLP. Apoptosis and neutrophil infiltration were increased in the pancreas of septic KO mice (p < 0.05, vs septic WT mice), with lower Bcl-2 and higher caspase-3 levels in septic KO mice (p < 0.05). Molecular analysis revealed increased NF-κB-p65 and phosphorylated IκB-α levels along with higher serum levels of TNF-α and IL-6 in septic KO mice compared to septic WT mice (p < 0.01). Furthermore, in vitro islet cultures stimulated with LPS produced higher TNF-α and IL-6 (p < 0.05) from KO mice compared to WT mice. Collectively, these results demonstrate SP-D plays protective roles by inhibiting apoptosis and modulating NF-κB-mediated inflammation in CLP-induced API.

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Protective Role of Surfactant Protein D in Ocular Staphylococcus aureus Infection

Cited by 22 publications

References 54 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

Surfactant protein D attenuates acute lung and kidney injuries in pneumonia-induced sepsis through modulating apoptosis, inflammation and NF-κB signaling

Innate Immune Molecule Surfactant Protein D Attenuates Sepsis-induced Acute Pancreatic Injury through Modulating Apoptosis and NF-κB-mediated Inflammation

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