Evasion of Neutrophil Killing by Staphylococcus aureus

McGuinness, Will A.; Kobayashi, Scott D.; DeLeo, Frank R.

doi:10.3390/pathogens5010032

Cited by 62 publications

(68 citation statements)

References 98 publications

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“…Necrosis, netosis, and necroptosis have also been described as pro‐inflammatory types of death . While phagocytosis‐induced cell death is desirable for the resolution of infection and prevention of prolonged inflammation, this process can be diverted by pathogens such as Staphylococcus aureus , Streptococcus pyogenes , or Francisella tularensis …”

Section: Investigation Of Cytosolic Pcna In Neutrophilsmentioning

confidence: 99%

“…58 Necrosis, netosis, and necroptosis 59 have also been described as pro-inflammatory types of death. 60 While phagocytosis-induced cell death is desirable for the resolution of infection and prevention of prolonged inflammation, this process can be diverted by pathogens such as Staphylococcus aureus, 61,62 Streptococcus pyogenes, 63 or Francisella tularensis. 64 Another parameter that greatly affects neutrophil function is the level of oxygenation 65 : indeed, in hypoxia, neutrophils are protected from apoptosis via a mechanism dependent on the hypoxia-inducible factor (HIF)-1α subunit of the oxygen-sensitive transcription factor HIF.…”

Section: Tight Regulation Of the Balance Between Survival And Deathmentioning

confidence: 99%

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Proliferating cell nuclear antigen in neutrophil fate

Witko‐Sarsat

Ohayon

2016

Immunological Reviews

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The life span of a neutrophil is a tightly regulated process as extended survival is beneficial for pathogen elimination and cell death necessary to prevent cytotoxic content release from activated neutrophils at the inflammatory site. Therefore, the control between survival and death must be a dynamic process. We have previously described that proliferating cell nuclear antigen (PCNA) which is known as a nuclear protein pivotal in DNA synthesis, is a key element in controlling neutrophil survival through its association with procaspases. Contrary to the dogma which asserted that PCNA has a strictly nuclear function, in mature neutrophils, PCNA is present exclusively within the cytosol due to its nuclear export at the end of the granulocytic differentiation. More recent studies are consistent with the notion that the cytosolic scaffold of PCNA is aimed at modulating neutrophil fate rather than simply preventing death. Ultimately, targeting neutrophil survival might have important applications not just in the field of immunology and inflammation, but also in hematology and transfusion. The neutrophil emerges as a unique and powerful cellular model to unravel the basic mechanisms governing the cell cycle-independent functions of PCNA and should be considered as a leader of the pack.

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Section: Investigation Of Cytosolic Pcna In Neutrophilsmentioning

confidence: 99%

Section: Tight Regulation Of the Balance Between Survival And Deathmentioning

confidence: 99%

Proliferating cell nuclear antigen in neutrophil fate

Witko‐Sarsat

Ohayon

2016

Immunological Reviews

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“…agr is an important regulator of virulence and is also a TCS consisting of the response regulator AgrA and the kinase AgrC. The SaeR/S TCS in essential to the evasion of the innate immune system by reducing reactive oxygen species, aiding survival in the face of host defense peptides, reducing expression of IL-8, and increasing the expression of leukocidins [32, 40, 42, 189, 190]. SaeRS can also regulate the expression of virulence genes including hla [191].…”

Section: Two-component Systemsmentioning

confidence: 99%

Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics

Kane

Carothers

Lee

2018

CDT

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Background Staphylococcus aureus is a major bacterial pathogen capable of causing a range of infections in humans from gastrointestinal disease, skin and soft tissue infections, to severe outcomes such as sepsis. Staphylococcal infections in humans can be frequent and recurring, with treatments becoming less effective due to the growing persistence of antibiotic resistant S. aureus strains. Due to the prevalence of antibiotic resistance, and the current limitations on antibiotic development, an active and highly promising avenue of research has been to develop strategies to specifically inhibit the activity of virulence factors produced S. aureus as an alternative means to treat disease. Objective In this review we specifically highlight several major virulence factors produced by S. aureus for which recent advances in antivirulence approaches may hold promise as an alternative means to treating diseases caused by this pathogen. Strategies to inhibit virulence factors can range from small molecule inhibitors, to antibodies, to mutant and toxoid forms of the virulence proteins. Conclusion The major prevalence of antibiotic resistant strains of S. aureus combined with the lack of new antibiotic discoveries highlight the need for vigorous research into alternative strategies to combat diseases caused by this highly successful pathogen. Current efforts to develop specific antivirulence strategies, vaccine approaches, and alternative therapies for treating severe disease caused by S. aureus have the potential to stem the tide against the limitations that we face in the post-antibiotic era.

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“…Accordingly, Ly6G + cells were observed more frequently in the clump of FITC-positive S. aureus in the KRT-treated group at 6 h post-injection, and the histological images of FITC-positive S. aureus clumps were evidently fewer in KRT-treated group than that of control group (Figure 3). Circulating neutrophils are recruited rapidly to infectious areas through chemotactic signals and eliminate bacteria by bactericidal and phagocytic mechanisms [2,3,26] . Depletion of neutrophils delays bacterial clearance and causes lethality in mouse lung infection [27] .…”

Section: Ly6gmentioning

confidence: 99%

“…Circulating neutrophils are rapidly recruited to infectious areas through chemotactic signals [2] . Neutrophils dominantly express va rious receptors for PAMPs and bear the primary defense against infection by killing bacteria through some bactericidal mechanisms [3] .…”

Section: Introductionmentioning

confidence: 99%

Keigairengyoto, a traditional Japanese medicine, promotes bacterial clearance by activating innate immune cells in mouse cutaneous infection models

et al. 2017

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Prompt elimination of pathogens including bacteria and dead cells prevents the expansion of secondary and prolonged inflammations and tissue damage. Keigairengyoto (KRT) is a traditional Japanese medicine prescribed for dermatoses such as purulent inflammations. Our aim is to clarify the actions of KRT in bacterial clearance and to examine the cell-kinetic profiles of phagocytes. In a mouse cutaneous infection model using living Staphylococcus aureus, KRT drastically reduced the number of bacteria in the infection sites. To evaluate the bacterial clearance, pseudo-infection was induced in mouse ears by intradermal injection of FITC-conjugated dead S. aureus. Biochemical and histological examinations revealed that KRT promoted bacterial clearance at 6 and 24 h post-injection. The numbers and phagocytic activities of neutrophils and macrophages in the ears were evaluated histologically using anti-Ly6G and F4/80 antibodies. KRT reduced bacterial deposition and increased the accumulation of F4/80 + resident macrophages around the lesion site. FACS analysis was performed on single cell suspensions dispersed enzymatically from skin lesions, followed by an investigation of CD11b + Ly6G + (neutrophils) and CD11b + Ly6G -(monocytes/macrophages) cells. KRT increased the mean fluorescent intensity of FITC in CD11b Ly6G-cells and the number of FITCpositive CD11b + Ly6G+ cells, while KRT did not change the numbers of these cells. To investigate the active constituents of KRT, phagocytosis assay using macrophages was performed, resulting in that some flavonoid glucuronides of KRT derivatives augmented phagocytosis. Collectively, KRT promoted bacterial clearance by enhancing the phagocytic capability of neutrophils and macrophages. KRT may exert unique properties in preventive and therapeutic strategies for skin infectious inflammation.

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Evasion of Neutrophil Killing by Staphylococcus aureus

Cited by 62 publications

References 98 publications

Proliferating cell nuclear antigen in neutrophil fate

Proliferating cell nuclear antigen in neutrophil fate

Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics

Keigairengyoto, a traditional Japanese medicine, promotes bacterial clearance by activating innate immune cells in mouse cutaneous infection models

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