2023
DOI: 10.1111/mmi.15026
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Specific preadaptations of Rhodococcus equi cooperate with its Virulence‐associated protein A during macrophage infection

Abstract: Rhodococcus equi (Prescotella equi;Sangal et al., 2022) is a Grampositive actinomycete, a close relative of pathogenic mycobacteria, and both an environmental soil bacterium and a facultative intracellular pathogen. It can cause life-threatening pulmonary infections in young foals and in immunocompromised humans, particularly in

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Cited by 4 publications
(6 citation statements)
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“…Since we find VapA has similar lysosomal disruptive properties to VapK, and VapB has limited lysosomal disruptive properties, the binding of VapA to phosphatidic acid may be an artefactual property of VapA. The modest permeabilisation of liposomes with VapA [48] is not recapitulated to the same extent with VapB or VapN, suggesting that this observation may also be an effect which is unrelated to the true biological activity of VapA. Furthermore, VapA is found primarily localising to intracellular membranes [37] and not the phagolysosomal limiting membrane (which we also see in Figure S5), and so it is unclear how membrane permeabilisation would occur if VapA is bound to lumenal-vesicular membranes.…”
Section: Discussionmentioning
confidence: 75%
See 1 more Smart Citation
“…Since we find VapA has similar lysosomal disruptive properties to VapK, and VapB has limited lysosomal disruptive properties, the binding of VapA to phosphatidic acid may be an artefactual property of VapA. The modest permeabilisation of liposomes with VapA [48] is not recapitulated to the same extent with VapB or VapN, suggesting that this observation may also be an effect which is unrelated to the true biological activity of VapA. Furthermore, VapA is found primarily localising to intracellular membranes [37] and not the phagolysosomal limiting membrane (which we also see in Figure S5), and so it is unclear how membrane permeabilisation would occur if VapA is bound to lumenal-vesicular membranes.…”
Section: Discussionmentioning
confidence: 75%
“…All these data indicate that there is a good correlation between the ability of certain Vaps to disrupt late endocytic pathway acidity, reduce lysosomal proteolytic activity, and then accumulate undigested material resulting in large endolysosomes which fail to condense and reform terminal lysosomes. While R. equi may be adapted to survive short term in a phagolysosomal environment [48], bacterial replication will be dependent upon the reduction of hydrolase activity. Our data show that in an environment with VapA-induced alkalynisation of the compartment, the compartment remains fusogenic, thereby maintaining the delivery of nutrients to the phagolysosomal compartment that can be utilised by R. equi.…”
Section: Discussionmentioning
confidence: 99%
“…11,49,52,53 Recombinant VapA (rVapA) restores the ability to replicate intracellularly to avirulent R. equi (-pVAPA or Δ απΑ ). [53][54][55] VapA inhibition of bacterial killing capacity of macrophages requires the bacteria to have specific preadaptation and rVapA does not promote replication for the majority of other bacteria examined. 55 However, rVapA supplementation has been shown to enhance intracellular persistence of nonpathogenic E. coli in J774A.1 cells.…”
Section: Rhodococcus Equimentioning
confidence: 99%
“…[53][54][55] VapA inhibition of bacterial killing capacity of macrophages requires the bacteria to have specific preadaptation and rVapA does not promote replication for the majority of other bacteria examined. 55 However, rVapA supplementation has been shown to enhance intracellular persistence of nonpathogenic E. coli in J774A.1 cells. 53 Despite decades of research, the mechanism of action of VapA has not been fully elucidated.…”
Section: Rhodococcus Equimentioning
confidence: 99%
“…VapA is the only Vap protein for which a role in virulence has been demonstrated (Giguere et al., 1999; Jain et al., 2003; von Bargen et al., 2019), but the expression of the vapA gene in place of the virulence plasmid is not sufficient to cause disease (Coulson et al., 2015; Giguere et al., 1999). The expression of vapA within the phagosome is promoted when the environmental pH becomes acidic and the temperatures raise to above 34°C, providing cues for the presence of a host environment (Haubenthal et al., 2023; Kakuda et al., 2015).…”
Section: Introductionmentioning
confidence: 99%