Bacterial Pathogens versus Autophagy: Implications for Therapeutic Interventions

Kimmey, Jacqueline M.; Stallings, Christina L.

doi:10.1016/j.molmed.2016.10.008

Cited by 134 publications

(122 citation statements)

References 144 publications

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“…Of these, S. flexneri, the most closely related to Salmonella, also replicates within the cytosol of intestinal epithelial cells. Both rely on T3SS-mediated pore formation to escape from the vacuole, but this is a double-edged sword since it is also a potent activator of host cytosolic defenses (Kimmey and Stallings, 2016). Specifically, bacteria are subject to a variation of autophagy known as xenophagy, an evolutionarily conserved mechanism, which controls Salmonella replication (Birmingham et al, 2006;Jia et al, 2009;Benjamin et al, 2013;Conway et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

A role for the Salmonella Type III Secretion System 1 in bacterial adaptation to the cytosol of epithelial cells

Chong

Starr

Finn

et al. 2019

Molecular Microbiology

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Summary Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that invades the intestinal epithelium. Following invasion of epithelial cells, Salmonella survives and replicates within two distinct intracellular niches. While all of the bacteria are initially taken up into a membrane bound vacuole, the Salmonella‐containing vacuole or SCV, a significant proportion of them promptly escape into the cytosol. Cytosolic Salmonella replicates more rapidly compared to the vacuolar population, although the reasons for this are not well understood. SipA, a multi‐function effector protein, has been shown to affect intracellular replication and is secreted by cytosolic Salmonella via the invasion‐associated Type III Secretion System 1 (T3SS1). Here, we have used a multipronged microscopy approach to show that SipA does not affect bacterial replication rates per se, but rather mediates intra‐cytosolic survival and/or initiation of replication following bacterial egress from the SCV. Altogether, our findings reveal an important role for SipA in the early survival of cytosolic Salmonella.

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Section: Discussionmentioning

confidence: 99%

A role for the Salmonella Type III Secretion System 1 in bacterial adaptation to the cytosol of epithelial cells

Chong

Starr

Finn

et al. 2019

Molecular Microbiology

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“…We therefore conclude that the observed autophagic processes that promote intracellular replication of Y. enterocolitica require induction of canonical macroautophagy pathways distinct from LAP. Huang & Brumell, 2014, Kimmey & Stallings, 2016. The mechanisms, by which these bacteria subvert or hijack autophagy pathways are, however, mostly unclear (Huang & Brumell, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…consequence evolved mechanisms to evade or modulate autophagyrelated pathways for their own benefit to establish disease (Huang & Brumell, 2014;Kimmey & Stallings, 2016;Kohler & Roy, 2017;Mostowy & Cossart, 2012).…”

mentioning

confidence: 99%

Activation of the macroautophagy pathway byYersinia enterocoliticapromotes intracellular multiplication and egress of yersiniae from epithelial cells

Lopez

Schimmeck

Gropengießer

et al. 2019

Cellular Microbiology

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The virulence strategy of pathogenic Yersinia spp. involves cell-invasive as well as phagocytosis-preventing tactics to enable efficient colonisation of the host organism.Enteropathogenic yersiniae display an invasive phenotype in early infection stages, which facilitates penetration of the intestinal mucosa. Here we show that invasion of epithelial cells by Yersinia enterocolitica is followed by intracellular survival and multiplication of a subset of ingested bacteria. The replicating bacteria were enclosed in vacuoles with autophagy-related characteristics, showing phagophore formation, xenophagy, and recruitment of cytoplasmic autophagosomes to the bacteriacontaining compartments. The subsequent fusion of these vacuoles with lysosomes and concomitant vesicle acidification were actively blocked by Yersinia. This resulted in increased intracellular proliferation and detectable egress of yersiniae from infected cells. Notably, deficiency of the core autophagy machinery component FIP200 impaired the development of autophagic features at Yersinia-containing vacuoles as well as intracellular replication and release of bacteria to the extracellular environment. These results suggest that Y. enterocolitica may take advantage of the macroautophagy pathway in epithelial cells to create an autophagosomal niche that supports intracellular bacterial survival, replication, and, eventually, spread of the bacteria from infected cells.

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“…Importantly, results from Yoshikawa et al (2009) suggested that the ability of ActA to prevent recognition of L. monocytogenes by autophagy is independent of actin polymerization and actin-based motility. Although the conclusions of Yoshikawa et al (2009) dominate the current literature (Choy and Roy, 2013; Gong et al , 2012; Huang and Brumell, 2014; Kimmey and Stallings, 2016; Mostowy, 2013; Mostowy and Shenoy, 2015; Pareja and Colombo, 2013; Welch and Way, 2013), it is still unclear if actin polymerization and actin-based motility play a role in the avoidance of L. monocytogenes from autophagy during macrophage infection.…”

Section: Introductionmentioning

confidence: 99%

“…Although the conclusions of Yoshikawa et al (2009) dominate the current literature (Choy & Roy, 2013;Gong, Devenish, & Prescott, 2012;Huang & Brumell, 2014;Kimmey & Stallings, 2016;Mostowy, 2013;Mostowy & Shenoy, 2015;Pareja & Colombo, 2013;Welch & Way, 2013), it is still unclear if actin polymerisation and actin-based motility play a role in the avoidance of L. monocytogenes from autophagy during macrophage infection.…”

mentioning

confidence: 99%

Actin‐based motility allows Listeria monocytogenes to avoid autophagy in the macrophage cytosol

Cheng

Chen

Engström

et al. 2018

Cellular Microbiology

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Listeria monocytogenes grows in the host cytosol and uses the surface protein ActA to promote actin polymerisation and mediate actin-based motility. ActA, along with two secreted bacterial phospholipases C, also mediates avoidance from autophagy, a degradative process that targets intracellular microbes. Although it is known that ActA prevents autophagic recognition of L. monocytogenes in epithelial cells by masking the bacterial surface with host factors, the relative roles of actin polymerisation and actin-based motility in autophagy avoidance are unclear in macrophages. Using pharmacological inhibition of actin polymerisation and a collection of actA mutants, we found that actin polymerisation prevented the colocalisation of L. monocytogenes with polyubiquitin, the autophagy receptor p62, and the autophagy protein LC3 during macrophage infection. In addition, the ability of L. monocytogenes to stimulate actin polymerisation promoted autophagy avoidance and growth in macrophages in the absence of phospholipases C. Time-lapse microscopy using green fluorescent protein-LC3 macrophages and a probe for filamentous actin showed that bacteria undergoing actin-based motility moved away from LC3-positive membranes. Collectively, these results suggested that although actin polymerisation protects the bacterial surface from autophagic recognition, actin-based motility allows escape of L. monocytogenes from autophagic membranes in the macrophage cytosol.

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Bacterial Pathogens versus Autophagy: Implications for Therapeutic Interventions

Cited by 134 publications

References 144 publications

A role for the Salmonella Type III Secretion System 1 in bacterial adaptation to the cytosol of epithelial cells

A role for the Salmonella Type III Secretion System 1 in bacterial adaptation to the cytosol of epithelial cells

Activation of the macroautophagy pathway byYersinia enterocoliticapromotes intracellular multiplication and egress of yersiniae from epithelial cells

Actin‐based motility allows Listeria monocytogenes to avoid autophagy in the macrophage cytosol

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