Maintenance of vacuole integrity by bacterial pathogens

Creasey, Elizabeth A.; Isberg, Ralph R.

doi:10.1016/j.mib.2013.11.005

Cited by 54 publications

(50 citation statements)

References 54 publications

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“…Many microbial pathogens occupy membrane-bound compartments within infected cells, which often shield them from detection by cytoplasmic sensor or protect them from cytoplasmic antimicrobial factors (Creasey and Isberg, 2014). Pathogens that enter the endocytic network, however, must subvert membrane traffic to avoid transport to degradative intracellular compartments.…”

Section: Discussionmentioning

confidence: 99%

A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP

Spanò

Gao

Hannemann

et al. 2016

Cell Host & Microbe

108

146

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Summary Cell-autonomous defense mechanisms are potent strategies that protect individual cells against intracellular pathogens. The Rab-family GTPase Rab32 was previously shown to restrict the intracellular human pathogen Salmonella Typhi, but its potential broader role in antimicrobial defense remains unknown. We show that Rab32 represents a general cell-autonomous, antimicrobial defense that is counteracted by two Salmonella effectors. Mice lacking Rab-32 or its nucleotide exchange factor BLOC-3 are permissive to S. Typhi infection and exhibit increased susceptibility to S. Typhimurium. S. Typhimurium counters this defense pathway by delivering two type III secretion effectors, SopD2, a Rab32 GAP, and GtgE, a specific Rab32 protease. An S. Typhimurium mutant strain lacking these two effectors exhibits markedly reduced virulence, which is fully restored in BLOC-3-deficient mice. These results demonstrate that a cell-autonomous, Rab32-dependent host defense pathway plays a central role in the defense against vacuolar pathogens and describe a mechanism evolved by a bacterial pathogen to counter it.

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Section: Discussionmentioning

confidence: 99%

A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP

Spanò

Gao

Hannemann

et al. 2016

Cell Host & Microbe

108

146

View full text Add to dashboard Cite

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“…Although active egress from PVs is occasionally executed by vacuolar pathogens as a strategy to promote intracellular replication, loss of membrane integrity may also occur as an unintended consequence of PV manipulations by resident bacteria (5). Previous studies have demonstrated that PV membrane remodeling and manipulations of PV trafficking by secreted effector proteins can stabilize and destabilize PV membranes (7)(8)(9).…”

Section: Mouse and Human Gbps Colocalize With Galectin-3 At Sterilelymentioning

confidence: 99%

“…For example, some bacterial effectors modify the lipid composition of PVs. As a potential consequence of these lipid modifications, PVs are more likely to rupture when exposed to cytoskeleton motor-dependent mechanical forces (5,6). Although pathogens such as Legionella pneumophila or Salmonella enterica secrete effectors to counteract destabilizing effects of membrane manipulations to maintain the PV as a replicative niche (7)(8)(9), subsets of Legionella-containing vacuoles (LCVs) or Salmonella-containing vacuoles (SCVs) nonetheless fail to maintain their membrane integrity (7,10).…”

mentioning

confidence: 99%

Galectin-3 directs antimicrobial guanylate binding proteins to vacuoles furnished with bacterial secretion systems

Feeley

Pilla-Moffett

Zwack

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

125

155

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Many invasive bacteria establish pathogen-containing vacuoles (PVs) as intracellular niches for microbial growth. Immunity to these infections is dependent on the ability of host cells to recognize PVs as targets for host defense. The delivery of several host defense proteins to PVs is controlled by IFN-inducible guanylate binding proteins (GBPs), which themselves dock to PVs through poorly characterized mechanisms. Here, we demonstrate that GBPs detect the presence of bacterial protein secretion systems as “patterns of pathogenesis” associated with PVs. We report that the delivery of GBP2 to Legionella-containing vacuoles is dependent on the bacterial Dot/Icm secretion system, whereas the delivery of GBP2 to Yersinia-containing vacuoles (YCVs) requires hypersecretion of Yersinia translocon proteins. We show that the presence of bacterial secretion systems directs cytosolic carbohydrate-binding protein Galectin-3 to PVs and that the delivery of GBP1 and GBP2 to Legionella-containing vacuoles or YCVs is substantially diminished in Galectin-3–deficient cells. Our results illustrate that insertion of bacterial secretion systems into PV membranes stimulates Galectin-3–dependent recruitment of antimicrobial GBPs to PVs as part of a coordinated host defense program.

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“…Therefore, maintenance of the integrity of bacteria-containing vacuoles is essential for intravacuolar bacterial pathogens. Accordingly, recent studies suggest that intravacuolar bacteria target multiple host components and signaling pathways to maintain the stability of their residing vacuoles (164, 165). …”

Section: Infection Of Macrophages By Intravacuolar Bacteriamentioning

confidence: 99%

Strategies Used by Bacteria to Grow in Macrophages

Mitchell

Chen²,

Portnoy

2016

Microbiol Spectr

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Intracellular bacteria are often clinically relevant pathogens that infect virtually every cell type found in host organisms. However, myeloid cells, especially macrophages, constitute the primary cells targeted by most species of intracellular bacteria. Paradoxically, macrophages possess an extensive antimicrobial arsenal and are efficient at killing microbes. In addition to their ability to detect and signal the presence of pathogens, macrophages sequester and digest microorganisms using the phagolysosomal and autophagy pathways or, ultimately, eliminate themselves through the induction of programmed cell death. Consequently, intracellular bacteria influence numerous host processes and deploy sophisticated strategies to replicate within these host cells. Although most intracellular bacteria have a unique intracellular life cycle, these pathogens are broadly categorized into intravacuolar and cytosolic bacteria. Following phagocytosis, intravacuolar bacteria reside in the host endomembrane system and, to some extent, are protected from the host cytosolic innate immune defenses. However, the intravacuolar lifestyle requires the generation and maintenance of unique specialized bacteria-containing vacuoles and involves a complex network of host-pathogen interactions. Conversely, cytosolic bacteria escape the phagolysosomal pathway and thrive in the nutrient-rich cytosol despite the presence of host cell-autonomous defenses. The understanding of host-pathogen interactions involved in the pathogenesis of intracellular bacteria will continue to provide mechanistic insights into basic cellular processes and may lead to the discovery of novel therapeutics targeting infectious and inflammatory diseases.

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Maintenance of vacuole integrity by bacterial pathogens

Cited by 54 publications

References 54 publications

A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP

A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP

Galectin-3 directs antimicrobial guanylate binding proteins to vacuoles furnished with bacterial secretion systems

Strategies Used by Bacteria to Grow in Macrophages

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