Molecular Mechanisms of Host Cytoskeletal Rearrangements by Shigella Invasins

Lee, Jun Hyuck; Park, HaJeung; Park, Taesung

doi:10.3390/ijms151018253

Cited by 19 publications

(13 citation statements)

References 79 publications

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“…Shigella invasion of cells requires the translocation of bacterial effector proteins through the translocon pore into the cytosol. The translocated effectors induce actin rearrangements, which in turn generate membrane ruffles that engulf the bacteria (17–19). The effect of cysteine substitutions in IpaC on S.…”

Section: Resultsmentioning

confidence: 99%

Topological Analysis of the Type 3 Secretion System Translocon Pore Protein IpaC following Its Native Delivery to the Plasma Membrane during Infection

Russo

Duncan

Goldberg

2019

mBio

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Many Gram-negative bacterial pathogens require a type 3 secretion system (T3SS) to deliver effector proteins into eukaryotic cells. Contact of the tip complex of the T3SS with a target eukaryotic cell initiates secretion of the two bacterial proteins that assemble into the translocon pore in the plasma membrane. The translocon pore functions to regulate effector protein secretion and is the conduit for effector protein translocation across the plasma membrane. To generate insights into how the translocon pore regulates effector protein secretion, we defined the topology of the Shigella translocon pore protein IpaC in the plasma membrane following its native delivery by the T3SS. Using single cysteine substitution mutagenesis and site-directed labeling with a membrane-impermeant chemical probe, we mapped residues accessible from the extracellular surface of the cell. Our data support a model in which the N terminus of IpaC is extracellular and the C terminus of IpaC is intracellular. These findings resolve previously conflicting data on IpaC topology that were based on nonnative delivery of IpaC to membranes. Salmonella enterica serovar Typhimurium also requires the T3SS for effector protein delivery into eukaryotic cells. Although the sequence of IpaC is closely related to the Salmonella translocon pore protein SipC, the two proteins have unique functional attributes during infection. We showed a similar overall topology for SipC and IpaC and identified subtle topological differences between their transmembrane α-helixes and C-terminal regions. Together, our data suggest that topological differences among distinct translocon pore proteins may dictate organism-specific functional differences of the T3SSs during infection. IMPORTANCE The type 3 secretion system (T3SS) is a nanomachine required for virulence of many bacterial pathogens that infect humans. The system delivers bacterial virulence proteins into the cytosol of human cells, where the virulence proteins promote bacterial infection. The T3SS forms a translocon pore in the membranes of target cells. This pore is the portal through which bacterial virulence proteins are delivered by the T3SS into the eukaryotic cytosol. The pore also regulates secretion of these virulence proteins. Our work defines the topology of translocon pore proteins in their native context during infection, resolves previously conflicting reports about the topology of the Shigella translocon pore protein IpaC, and provides new insights into how interactions of the pore with the T3SS likely produce signals that activate secretion of virulence proteins.

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Section: Resultsmentioning

confidence: 99%

Topological Analysis of the Type 3 Secretion System Translocon Pore Protein IpaC following Its Native Delivery to the Plasma Membrane during Infection

Russo

Duncan

Goldberg

2019

mBio

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“…Shigella invasion of cells requires the translocation of bacterial effector proteins through the translocon pore into the cytosol. The translocated effectors induce actin rearrangements, which in turn generate membrane ruffles that engulf the bacteria (17-19). The effect of cysteine substitutions in IpaC on S. flexneri invasion was tested by quantifying the numbers of bacteria internalized during infection of HeLa cells (7).…”

Section: Resultsmentioning

confidence: 99%

Topological analysis of the type 3 secretion system translocon pore protein IpaC following its native delivery to the plasma membrane during infection

Russo

Duncan²,

Goldberg

2019

Preprint

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word count: 248 words Text word count: 5,371 words Abstract 1Many Gram-negative bacterial pathogens require a type 3 secretion system 2 (T3SS) to deliver effector proteins into eukaryotic cells. Contact of the tip complex of the 3 T3SS with a target eukaryotic cell initiates the secretion of the two bacterial proteins that 4 assemble into the translocon pore in the plasma membrane. The translocon pore 5 functions to regulate effector protein secretion and is the conduit for effector protein 6 translocation across the plasma membrane. To generate insights into how the 7 translocon pore regulates effector protein secretion, we defined the topology of the 8 Shigella translocon pore protein IpaC in the plasma membrane following its native 9 delivery by the T3SS. Using single-cysteine substitution mutagenesis and site-directed 10 labeling with a membrane-impermeant chemical probe, we mapped residues accessible 11 from the extracellular surface of the cell. Our data support a model in which the N-12 terminus of IpaC is extracellular and the C-terminus of IpaC is intracellular. These 13 findings resolve previously conflicting data on IpaC topology that were based on non-14

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“…Results herein and elsewhere (Fisher et al 2014;Vyas et al 2015) suggest that CLso-induced cytoskeletal rearrangement is necessary for systemic psyllid invasion or infection. A similar invasion strategy is used by bacterial pathogens of mammalian (Lee et al 2014) and phytophagous insect (Duret et al 2014;Hogenhout et al 2008) hosts, and also by circulative, propagative plant viruses in their insect hosts (Badillo-Vargas et al 2012;Hogenhout et al 2003;Whitfield et al 2005). Finally, the expression of psyllid-encoded clathrin, profilin, Rac 1, talin, and vinculin gene products previously implicated as Liberibacter-PoP interactors with predicted involvement in systemic invasion (Fisher et al 2014;Vyas et al 2015) is consistent with the observations reported herein during different stages of PoP infection by 'Ca.…”

Section: Discussionmentioning

confidence: 99%

Colonization and Intrusive Invasion of Potato Psyllid by ‘Candidatus Liberibacter solanacearum’

et al. 2017

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Previous studies have shown that the fastidious bacterial plant pathogen 'Candidatus Liberibacter solanacearum' (CLso) is transmitted circulatively and propagatively by the potato psyllid (PoP) Bactericera cockerelli. In this study, the temporal and spatial interrelationships between CLso PoP were investigated by scanning electron microscopy of the digestive system of PoP immature and adult instars and salivary glands of adults post CLso ingestion. CLso biofilms were not detectable on the outer midgut surface of the first and second instars; however, for third to fifth instars and teneral and mature adults, biofilms were observed in increasing numbers in each successive developmental stage. In adult PoP midguts, CLso cells were observed between the basal lamina and basal epithelial cell membranes; in basal laminar perforations, on the outer basal laminar surface, and in the ventricular lumen, epithelial cytosol, and filter chamber periventricular space. CLso were also abundantly visible in the salivary gland pericellular spaces and in the epidermal cell cytosol of the head. Collectively, these results point to an intrusive, systemic invasion of PoP by CLso that employs an endo/exocytosis-like mechanism, in the context of a propagative, circulative mode of transmission.

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Molecular Mechanisms of Host Cytoskeletal Rearrangements by Shigella Invasins

Cited by 19 publications

References 79 publications

Topological Analysis of the Type 3 Secretion System Translocon Pore Protein IpaC following Its Native Delivery to the Plasma Membrane during Infection

Topological Analysis of the Type 3 Secretion System Translocon Pore Protein IpaC following Its Native Delivery to the Plasma Membrane during Infection

Topological analysis of the type 3 secretion system translocon pore protein IpaC following its native delivery to the plasma membrane during infection

Colonization and Intrusive Invasion of Potato Psyllid by ‘Candidatus Liberibacter solanacearum’

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