Molecular Mechanisms of Intercellular Dissemination of Bacterial Pathogens

Dowd, Georgina C.; Mortuza, Roman; Ireton, Keith

doi:10.1016/j.tim.2020.06.008

Cited by 27 publications

(44 citation statements)

References 91 publications

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“…Identifying the precise origins, composition and function of TCT membranes and cytoskeletal elements is an important line of investigation. Overall, CaTCT stands in stark contrast to cell-to-cell spreading of actin-motile invasive bacteria like L. monocytogenes and S. flexneri that must induce host membrane breaching followed by 'escape' into the host cytosol in every invaded cell before transitioning to its neighbour (Dowd, Mortuza and Ireton, 2021).…”

Section: Discussionmentioning

confidence: 99%

Trans-cellular tunnels induced by the fungal pathogen Candida albicans facilitate invasion through successive epithelial cells without host damage

Lachat

Pascault

Thibaut

et al. 2021

Preprint

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The opportunistic fungal pathogen Candida albicans is normally commensal, residing in the mucosa of most healthy individuals. In susceptible hosts, its filamentous hyphal form can invade epithelial layers leading to superficial or severe systemic infection. Invasion is mainly intracellular, though it causes no apparent damage to host cells. We investigated the invasive lifestyle of Candida albicansin vitro using live-cell imaging and the damage-sensitive reporter galectin-3. Quantitative single cell analysis showed that invasion can result in host membrane breaching at different stages of invasion and cell death, or in traversal of host cells without membrane breaching. Membrane labelling and three-dimensional volume electron microscopy revealed that hyphae can traverse several host cells within trans-cellular tunnels that are progressively remodelled and may undergo inflations linked to host glycogen stores, possibly during nutrient uptake. Thus, Candida albicans invade epithelial tissues by either inflicting or avoiding host damage, the latter facilitated by trans-cellular tunnelling.

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Section: Discussionmentioning

confidence: 99%

Trans-cellular tunnels induced by the fungal pathogen Candida albicans facilitate invasion through successive epithelial cells without host damage

Lachat

Pascault

Thibaut

et al. 2021

Preprint

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“…The actin cytoskeleton is targeted by many bacterial virulence proteins, which can cause both its polymerisation or depolymerisation. This can prevent ( Yersinia ) or promote ( Salmonella, Shigella ) internalisation of bacteria into host cells, subvert membrane trafficking ( Chlamydia ), induce bacterial motility in the cell cytoplasm ( Shigella, Listeria ) and provide structural support for vacuoles containing bacteria ( Coxiella, Chlamydia ) (Dowd, Mortuza, & Ireton, 2020; Jimenez, Chen, & Alto, 2016; Scidmore, 2011).…”

Section: Introductionmentioning

confidence: 99%

SteC and the intracellular Salmonella ‐induced F‐actin meshwork

Heggie

Černý

Holden

2021

Cellular Microbiology

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Salmonella enterica serovars infect a broad range of mammalian hosts including humans, causing both gastrointestinal and systemic diseases. Following uptake into host cells, bacteria replicate within vacuoles (Salmonella‐containing vacuoles; SCVs). Clusters of SCVs are frequently associated with a meshwork of F‐actin. This meshwork is dependent on the Salmonella pathogenicity island 2 encoded type III secretion system and its effector SteC. SteC contains a region with weak similarity to conserved subdomains of eukaryotic kinases and has kinase activity that is required for the formation of the F‐actin meshwork. Several substrates of SteC have been identified. In this mini‐review, we attempt to integrate these findings and propose a more unified model to explain SCV‐associated F‐actin: SteC (i) phosphorylates the actin sequestering protein Hsp27, which increases the local G‐actin concentration (ii) binds to and phosphorylates formin family FMNL proteins, which enables actin polymerisation and (iii) phosphorylates MEK, resulting in activation of the MEK/ERK/MLCK/Myosin II pathway, leading to F‐actin bundling. We also consider the possible physiological functions of SCV‐associated F‐actin and similar structures produced by other intracellular bacterial pathogens.

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“…SFG rickettsiae undergo cell-to-cell spread, a process in which they directly move into neighboring cells by traversing cell–cell junctions, preserving access to the host cytoplasm and protection from the humoral immune system (Palmer and Azad 2012 ; Lamason and Welch 2017 ; Dowd, Mortuza and Ireton 2020 ). Cell-to-cell spread has also been observed in L. monocytogenes and S. flexneri , which use the force of actin-based motility to propel themselves into the cell–cell junction creating a protrusion into the neighboring cell (Kuehl et al .…”

Section: Rickettsiae Employ Complex and Unique Intracellular Life Cycles To Establish Infectionmentioning

confidence: 99%

“…Cell-to-cell spread has also been observed in L. monocytogenes and S. flexneri , which use the force of actin-based motility to propel themselves into the cell–cell junction creating a protrusion into the neighboring cell (Kuehl et al . 2015 ; Lamason and Welch 2017 ; Dowd, Mortuza and Ireton 2020 ). This protrusion is then engulfed by the recipient cell, and the bacterium is taken up in a double-membrane vacuole.…”

Section: Rickettsiae Employ Complex and Unique Intracellular Life Cycles To Establish Infectionmentioning

confidence: 99%

The enigmatic biology of rickettsiae: recent advances, open questions and outlook

McGinn

Lamason

2021

Pathogens and Disease

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Rickettsiae are obligate intracellular bacteria that can cause life-threatening illnesses and are among the oldest known vector-borne pathogens. Members of this genus are extraordinarily diverse and exhibit a broad host range. To establish intracellular infection, Rickettsia species undergo complex, multistep life cycles that are encoded by heavily streamlined genomes. As a result of reductive genome evolution, rickettsiae are exquisitely tailored to their host cell environment but cannot survive extracellularly. This host-cell dependence makes for a compelling system to uncover novel host-pathogen biology, but it has also hindered experimental progress. Consequently, the molecular details of rickettsial biology and pathogenesis remain poorly understood. With recent advances in molecular biology and genetics, the field is poised to start unraveling the molecular mechanisms of these host-pathogen interactions. Here, we review recent discoveries that have shed light on key aspects of rickettsial biology. These studies have revealed that rickettsiae subvert host cells using mechanisms that are distinct from other better-studied pathogens, underscoring the great potential of the Rickettsia genus for revealing novel biology. We also highlight several open questions as promising areas for future study and discuss the path toward solving the fundamental mysteries of this neglected and emerging human pathogen.

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Molecular Mechanisms of Intercellular Dissemination of Bacterial Pathogens

Cited by 27 publications

References 91 publications

Trans-cellular tunnels induced by the fungal pathogen Candida albicans facilitate invasion through successive epithelial cells without host damage

Trans-cellular tunnels induced by the fungal pathogen Candida albicans facilitate invasion through successive epithelial cells without host damage

SteC and the intracellular Salmonella ‐induced F‐actin meshwork

The enigmatic biology of rickettsiae: recent advances, open questions and outlook

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