IndraLab

Statements


KCNMA1 activates GAST. 30 / 30
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"Taken together, these data indicate that induction of xenophagy is not required for efficient killing of GAS that are deficient in SLO and SLS, whereas SLO producing GAS exhibit enhanced intracellular survival despite inducing xenophagy."

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"Our study demonstrates that GAS has evolved two independent strategies to prevent bacterial recognition and maturation of DC : 1) inhibition of GAS internalization by the HA capsule, thus reducing intracellular sensing of streptococcal ligands, and 2) induction of DC apoptosis by intracellular SLO producing GAS."

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"These results illuminate the mechanisms through which SLO and NADase enable GAS to defeat macrophage mediated killing and provide new insight into the virulence of a major human pathogen."

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"Production of SLO prevented phagolysosomal acidification but was insufficient to support maximal GAS survival in the absence of enzymatically active NADase."

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"We conclude that the coordinated action of SLO and NADase disables macrophage bactericidal mechanisms and mediates GAS evasion of this key effector of host innate immunity."

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"In flow cytometry experiments, SLO producing GAS inhibited the uptake of fluorescent 70,000-MW dextran, but effective inhibition was only observed in keratinocytes that had bound GAS."

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"A previous study from our group showed that SLO deficient GAS rapidly co-localized with lysosomal markers after internalization by keratinocytes, whereas SLO producing GAS did not XREF_BIBR."

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"In addition, recent reports showed that SLO cooperates with NAD-glycohydrolase against lysosomal killing and prolongs the intracellular survival of GAS in keratinocytes and macrophages."

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"A recent report showed that SLO and NAD-glycohydrolase prevented phagolysosome acidification and promoted GAS survival in macrophages."

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"SLO production in tonsil colonising GAS was demonstrated with real time qRT-PCR using GAS RNA extracted from five selected GAS positive OSAS tonsils."

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"Production of the secreted CDC SLO is strongly associated with the capacity of GAS to incapacitate macrophage function : SLO producing GAS bacteria induce apoptosis of murine and human macrophages in vitro and resist macrophage mediated bacterial killing, in contrast to isogenic SLO deficient mutants."

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"However, SLO producing GAS were markedly more cytotoxic to HeLa cells, so it is likely that the low recovery of viable intracellular SLO producing GAS reflects loss of HeLa cell integrity and exposure of internalized GAS to antibiotic killing (XREF_SUPPLEMENTARY, C)."

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"We conclude that SLO stimulates xenophagy in pharyngeal keratinocytes, but the coordinated action of SLO and NADase prevent maturation of GAS containing autophagosomes, thereby prolonging GAS intracellular survival."

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"SLO promotes GAS resistance to phagocytic clearance by neutrophils, a critical first element of host defense against invasive bacterial infection."

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"A significant increase in the percentage of DC that exhibited hypodiploid nuclei was observed 20 h after exposure to live SLO producing GAS :> 35% of DC exposed to wild-type or acapsular GAS vs < 9% for untreated DC or DC exposed to SLO deficient GAS (P < 0.01)."

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"While SLO and NADase have been shown to enhance GAS intracellular survival in epithelial cells, the present data identify important differences in the mechanisms through which the toxins modulate GAS survival in macrophages."

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"In studies of GAS interactions with HeLa cells, Sakurai et al. also found that SLO production was associated with a failure of GAS containing early endosomes to colocalize with LAMP-1 and suggested that SLO producing GAS was released into the cytoplasm soon after internalization and later incorporated into autophagosomes."

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"SLO and ScpC independently enable GAS to escape from PMN functions; Present data using clinical isolated GAS and a scpC deletion mutant (XREF_FIG) show that enhanced production of serine proteinase ScpC in virulent GAS is essential to impair PMN migration in vitro by degradation of IL-8, as others partially have demonstrated XREF_BIBR - XREF_BIBR."

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"In addition, the cytotoxin SLO promoted escape of GAS from endosomes into the cytoplasm."

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"We conclude from these results that SLO production enhances GAS survival in human oropharyngeal keratinocytes, a cell type representative of the local environment occupied by GAS during human infection."

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"A 5-fold increase in the percentage of DC containing active caspases was observed immediately after a 2 h exposure to live wild-type SLO producing GAS compared to untreated DC or DC exposed to SLO deficient GAS (XREF_FIG)."

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"Supplying exogenous NADase partially rescued survival of 188 SLO-, a result that implies that SLO contributes to GAS intracellular survival in part through delivery of NADase, but also through function (s), such as pore formation, independent of NADase translocation."

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"The facts that SLO producing GAS bacteria are internalized poorly and that the internalization of these organisms is minimally affected by the blocking of clathrin or dynamin suggest that SLO targets the clathrin dependent internalization pathway."

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"SLO producing GAS cause sufficient damage to fully expose the bacteria to the cytosol and recruit the ubiquitin pathway."

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"Despite exerting a cytotoxic effect, several studies have reported that expression of SLO increases the recovery of GAS from epithelial cells compared to that of a SLO deficient strain."

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"After 20 h, caspase activation was significantly enhanced in DC exposed to SLO producing GAS, and DC containing active caspases also exhibited hypodiploid nuclei consistent with apoptosis."

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"By contrast, in a mouse model of bacterial sepsis after intraperitoneal inoculation of GAS, SLO expression enhanced the virulence of both encapsulated and acapsular GAS, whereas SLS expression increased the virulence only of acapsular GAS."

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"By contrast, Hakansson et al. found significantly greater intracellular survival of SLO producing GAS in human oropharyngeal keratinocytes in vitro compared to an isogenic SLO negative mutant XREF_BIBR."

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"In cells exposed to SLO producing GAS strain 188, the internalization of 70,000-MW dextran was reduced by 34% compared to that of cells exposed to 188SLO - (XREF_FIG)."

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"Exposure of keratinocytes to SLO producing GAS or to purified rSLO also inhibited the uptake of high-molecular-weight dextran, which is thought to be internalized by macropinocytosis."