How Bacteria Subvert Animal Cell Structure and Function

Jimenez, Alyssa; Chen, Didi; Alto, Neal M.

doi:10.1146/annurev-cellbio-100814-125227

Cited by 35 publications

(29 citation statements)

References 174 publications

(201 reference statements)

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“…The first is that, despite common features of infection, recent work has revealed surprising differences in the molecular mechanisms of actin-based motility. Older work showed a critical role for the host Arp2/3 complex and its nucleation promoting factors (NPFs) in actin assembly [9,10], but we are now learning that diverse biochemical mechanisms of actin polymerization are used by pathogens, resulting in divergent actin filament organization and parameters of motility. We are also learning that various host proteins regulate bacterial motility.…”

Section: Introductionmentioning

confidence: 99%

Actin-based motility and cell-to-cell spread of bacterial pathogens

Lamason

Welch

2017

Current Opinion in Microbiology

111

110

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Subversion of the host actin cytoskeleton is a critical virulence mechanism used by a variety of intracellular bacterial pathogens during their infectious life cycles. These pathogens manipulate host actin to promote actin-based motility and coordinate motility with cell-to-cell spread. Growing evidence suggests that the tactics employed by pathogens are surprisingly diverse. Here, we review recent advances suggesting that bacterial surface proteins exhibit divergent biochemical mechanisms of actin polymerization and recruit distinct host protein networks to drive motility, and that bacteria deploy secreted effector proteins that alter host cell mechanotransduction pathways to enable spread. Further investigation into the divergent strategies used by bacterial pathogens to mobilize actin will reveal new insights into pathogenesis and cytoskeleton regulation.

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Section: Introductionmentioning

confidence: 99%

Actin-based motility and cell-to-cell spread of bacterial pathogens

Lamason

Welch

2017

Current Opinion in Microbiology

111

110

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“…In addition, we identified 96 proteins in 44 host–pathogen common metabolic pathways as novel targets (Supplementary materials 4), among them ten protein targets were involved in bacterial secretion system pathway of E. faecium . Bacterial system secrete a wide range of proteins whose functions include biogenesis of organelles, bacterial growth and survival in eukaryotic host cells [41]. A total of 17 proteins were identified as unique in the pathogen specific pathway in a two-component system (KEGG Pathway: efu02020).…”

Section: Resultsmentioning

confidence: 99%

In Silicoidentification of potential drug targets by subtractive genome analysis ofEnterococcus faecium DO

Karim

Islam

Gmn

2020

Preprint

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Once believed to be a commensal bacteria, Enterococcus faecium has recently emerged as an important nosocomial pathogen worldwide. A recent outbreak of E. faecium unrevealed natural and in vitro resistance against a myriad of antibiotics namely ampicillin, gentamicin and vancomycin due to over-exposure of the pathogen to these antibiotics. This fact combined with the ongoing threat demands the identification of new therapeutic targets to combat E. faecium infections.In this present study, comparative proteome analysis, subtractive genomic approach, metabolic pathway analysis and additional drug prioritizing parameters were used to propose a potential novel drug targets for E. faecium strain DO. Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified a total of 207 putative target proteins in E. faecium DO that showed no similarity to human proteins. Among them 105 proteins were identified as essential novel proteins that could serve as potential drug targets through further bioinformatic approaches; such as-prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characterization. Eventually 19 non-homologous essential proteins of E. faecium DO were prioritized and proved to have the eligibility to become novel broad-spectrum antibiotic targets. Among these targets aldehyde-alcohol dehydrogenase was found to be involved in maximum pathways, and therefore, was chosen as novel drug target. Interestingly, aldehyde-alcohol dehydrogenase enzyme contains two domains namely acetaldehyde dehydrogenase and alcohol dehydrogenase, on which a 3D structure homology modeling and in silico molecular docking were performed. Finally, eight molecules were confirmed as the most suitable ligands for aldehyde-alcohol dehydrogenase and hence proposed as the potential inhibitors of this target.In conclusion, being human non-homologous, aldehyde-alcohol dehydrogenase protein can be targeted for potential therapeutic drug development in future. However, laboratory based experimental research should be performed to validate our findings in vivo.

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“…Membrane-bound cargo is transported within the host cell and to the extracellular space in dynamic vesicular trafficking pathways. The membrane-bound and soluble proteins important for these processes are frequent targets of bacterial effectors (47, 71). Indeed, Mtb is known to target and manipulate trafficking pathways through incompletely understood mechanisms (43, 72, 73).…”

Section: Resultsmentioning

confidence: 99%

“…Substrates of the accessory SecA2 system such as the protein kinase PknG and the esterase LipO are also important for Mtb virulence by contributing to phagosome maturation arrest (PMA) (13, 18, 45, 46). Thus, because membrane processes are high value targets of many bacterial effectors (39, 47), and Mtb has a large repertoire of exported proteins of unknown function (48-52), we hypothesized that some of the Mtb exported proteins are membrane-binding effectors with virulence activities.…”

Section: Introductionmentioning

confidence: 99%

Screening Mycobacterium tuberculosis secreted proteins identifies Mpt64 as eukaryotic membrane-binding virulence factor

Stamm

Pasko

Chaisavaneeyakorn

et al. 2018

Preprint

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word count: 203 22 23 2 Text word count: 7,901 24 3 Abstract 25Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is one of the 26 most successful human pathogens. One reason for its success is that Mtb can reside 27 within host macrophages, a cell type that normally functions to phagocytose and destroy 28 infectious bacteria. However, Mtb is able to evade macrophage defenses in order to 29 survive for prolonged periods of time. Many intracellular pathogens secret virulence 30 factors targeting host membranes and organelles to remodel their intracellular 31 environmental niche. We hypothesized that Mtb exported proteins that target host 32 membranes are vital for Mtb to adapt to and manipulate the host environment for 33 survival. Thus, we characterized 200 exported proteins from Mtb for their ability to 34 associate with eukaryotic membranes using a unique temperature sensitive yeast 35 screen and to manipulate host trafficking pathways using a modified inducible secretion 36 screen. We identified five Mtb exported proteins that both associated with eukaryotic 37 membranes and altered the host secretory pathway. One of these secreted proteins, 38Mpt64, localized to the endoplasmic reticulum during Mtb infection of murine and human 39 macrophages and was necessary for Mtb survival in primary human macrophages. 40

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How Bacteria Subvert Animal Cell Structure and Function

Cited by 35 publications

References 174 publications

Actin-based motility and cell-to-cell spread of bacterial pathogens

Actin-based motility and cell-to-cell spread of bacterial pathogens

In Silicoidentification of potential drug targets by subtractive genome analysis ofEnterococcus faecium DO

Screening Mycobacterium tuberculosis secreted proteins identifies Mpt64 as eukaryotic membrane-binding virulence factor

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