Intracellular <i>Staphylococcus aureus</i> eludes selective autophagy by activating a host cell kinase

Neumann, Yvonne; Bruns, Svenja Anne; Rohde, Manfred; Prajsnar, Tomasz K.; Foster, Simon J.; Schmitz, Ingo

doi:10.1080/15548627.2016.1226732

Cited by 96 publications

(123 citation statements)

References 59 publications

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“…However, there are no effective controls for S aureus mastitis so far and further research is needed. Autophagy is a cellular homeostatic mechanism in eukaryotes, which is as an effective mechanism for survival during cellular stress and also as an anti‐infective mechanism . In recent years, autophagy has been extensively studied as a defence mechanism against pathogen.…”

Section: Discussionmentioning

confidence: 99%

“…However, we found that the number of intracellular S aureus is gradually increased with CQ treatment, while S aureus replication in the cells is gradually reduced when Rap is used to enhance autophagy and autophagic flux is not blocked. Recently, it has been reported that in the S aureus ‐infected murine fibroblasts NIH/3T3, S aureus escapes phagocytic vacuoles and prevents further degradation by MAPK14/p38a MAP kinase‐mediated autophagy blockade . This difference may be due to the different escape mechanisms of S aureus in different cells.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been reported that in the S aureus-infected murine fibroblasts NIH/3T3, S aureus escapes phagocytic vacuoles and prevents further degradation by MAPK14/p38a MAP kinase-mediated autophagy blockade. 30 This difference may be due to the different escape mechanisms of S aureus in different cells.…”

Section: Discussionmentioning

confidence: 99%

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Staphylococcus aureus facilitates its survival in bovine macrophages by blocking autophagic flux

Cai

Zhou

et al. 2020

J Cellular Molecular Medi

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Staphylococcus aureus is a pathogen that is the causative agent of several human and veterinary infections and plays a critical role in the clinical and subclinical mastitis of cattle. Autophagy is a conserved pathogen defence mechanism in eukaryotes. Studies have reported that S aureus can subvert autophagy and survive in cells. Staphylococcus aureus survival in cells is an important cause of chronic persistent mastitis infection. However, it is unclear whether S aureus can escape autophagy in innate immune cells. In this study, initiation of autophagy due to the presence of S aureus was detected in bovine macrophages. We observed autophagic vacuoles increased after S aureus infection of bovine macrophages by transmission electron microscopy (TEM). It was also found that S aureus‐infected bovine macrophages increased the expression of LC3 at different times(0, 0.5, 1, 1.5, 2, 2.5, 3 and 4 hours). Data also showed the accumulation of p62 induced by S aureus infection. Application of autophagy regulatory agents showed that the degradation of p62 was blocked in S aureus induced bovine macrophages. In addition, we also found that the accumulation of autophagosomes promotes S aureus to survive in macrophage cells. In conclusion, this study indicates that autophagy occurs in S aureus‐infected bovine macrophages but is blocked at a later stage of autophagy. The accumulation of autophagosomes facilitates the survival of S aureus in bovine macrophages. These findings provide new insights into the interaction of S aureus with autophagy in bovine macrophages.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Staphylococcus aureus facilitates its survival in bovine macrophages by blocking autophagic flux

Cai

Zhou

et al. 2020

J Cellular Molecular Medi

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“…Thus, another compartment may exist in tissue cells that is replication permissive. For example, intracellular bacteria can be eliminated by xenophagy, a special form of autophagy (reviewed in Knodler & Celli, ), and it has been demonstrated that SaCP is targeted by autophagy (Schnaith et al, ; Mestre, Fader, Sola, & Colombo, ; Mestre & Colombo, ; Neumann et al, ). Interestingly, S .…”

Section: Getting “Out”: S Aureus Phagosomal Escape In Non‐professionmentioning

confidence: 99%

In or out: Phagosomal escape ofStaphylococcus aureus

Moldovan

Fraunholz

2019

Cellular Microbiology

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Staphylococcus aureus is internalised by host cells in vivo, and recent research results suggest that the bacteria use this intracellularity to persist in the host and form a reservoir for recurrent infections. However, in different cells types, the pathogen resorts to alternative strategies to survive phagocytosis and the antimicrobial mechanisms of host cells. In non‐professional phagocytes, S. aureus either escapes the endosome followed by cytoplasmic replication or replicates within autophagosomes. Professional phagocytes possess a limited capacity to kill S. aureus and hence the bacteria, well equipped with immune evasive mechanisms, replicate within the cells, eventually lyse out of the cells and thus persist in a continuous cycle of phagocytosis, host cell death, and bacterial release.

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“…To date, studies of autophagy on non-professional phagocytes infected with S. aureus provide conflicting results, with the core autophagic machinery shown to be either detrimental [21] or beneficial [22] to the infected host cells. Schnaith et al have shown that S. aureus is taken up within RAB7-positive phagosomes of mouse embryonic fibroblasts and subsequently is trapped within LC3-positive vesicles which serve as a niche for bacterial replication.…”

Section: Introductionmentioning

confidence: 99%

The autophagic response toStaphylococcus aureusprovides an intracellular niche in neutrophils

Prajsnar

Serba

Dekker

et al. 2019

Preprint

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Staphylococcus aureus is a major human pathogen causing multiple pathologies, from cutaneous lesions to life-threatening sepsis. Although neutrophils contribute to immunity against S. aureus, multiple lines of evidence suggest that these phagocytes can provide an intracellular niche for staphylococcal dissemination. However, the mechanism of neutrophil subversion by intracellular S. aureus remains unknown. Targeting of intracellular pathogens by autophagy is recognised as an important component of host innate immunity, but whether autophagy is beneficial or detrimental to S. aureus-infected hosts remains controversial. Here, using larval zebrafish we show that S. aureus is rapidly decorated by the autophagy marker Lc3 following engulfment by macrophages and neutrophils. Upon phagocytosis by neutrophils, Lc3-positive, non-acidified spacious phagosomes are formed. This response is dependent on phagocyte NADPH oxidase as both cyba knockdown and diphenyleneiodonium (DPI) treatment inhibited Lc3 decoration of phagosomes. Importantly, NADPH oxidase inhibition diverted neutrophil S. aureus processing into tight acidified vesicles, which resulted in increased host resistance to the infection. Some intracellular bacteria within neutrophils were also tagged by p62-GFP fusion protein and loss of p62 impaired host defence. Taken together, we have shown that intracellular handling of S. aureus by neutrophils is best explained by Lc3-associated phagocytosis (LAP), which appears to provide an intracellular niche for bacterial pathogenesis, while the selective autophagy receptor p62 is host-protective. The antagonistic roles of LAP and p62-mediated pathways in S. aureus-infected neutrophils may explain the conflicting reports relating to antistaphylococcal autophagy and provide new insights for therapeutic strategies against antimicrobial resistant staphylococci.

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Intracellular Staphylococcus aureus eludes selective autophagy by activating a host cell kinase

Cited by 96 publications

References 59 publications

Staphylococcus aureus facilitates its survival in bovine macrophages by blocking autophagic flux

Staphylococcus aureus facilitates its survival in bovine macrophages by blocking autophagic flux

In or out: Phagosomal escape ofStaphylococcus aureus

The autophagic response toStaphylococcus aureusprovides an intracellular niche in neutrophils

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