Beginning to Understand the Role of the Type IV Secretion System Effector Proteins in Coxiella burnetii Pathogenesis

Lührmann, Anja; Newton, Hayley J; Bonazzi, Matteo

doi:10.1007/978-3-319-75241-9_10

Cited by 27 publications

(34 citation statements)

References 107 publications

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“…Upon internalization by phagocytic and nonphagocytic cells, Coxiella remains in endosomes that progress in the endocytic pathway. Endosomal acidification triggers the activation of a defect in organelle trafficking genes/intracellular multiplication (Dot/Icm) type 4 secretion system (T4SS) and the translocation of bacterial effectors, which are essential for the biogenesis of the Coxiella-containing vacuole (CCV) [3][4][5]. Bioinformatics analysis and secretion assays using either Legionella [6] or Coxiella [7] have identified approximately 143 candidate Coxiella effectors [8].…”

Section: Introductionmentioning

confidence: 99%

Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence

et al. 2020

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2020): Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence, Autophagy, ABSTRACT Coxiella burnetii, the etiological agent of the zoonosis Q fever, replicates inside host cells within a large vacuole displaying autolysosomal characteristics. The development of this compartment is mediated by bacterial effectors, which interfere with a number of host membrane trafficking pathways. By screening a Coxiella transposon mutant library, we observed that transposon insertions in cbu0626 led to intracellular replication and vacuole biogenesis defects. Here, we demonstrate that CBU0626 is a novel member of the Coxiella vacuolar protein (Cvp) family of effector proteins, which is translocated by the Dot/Icm secretion system and localizes to vesicles with autolysosomal features as well as Coxiellacontaining vacuoles (CCVs). We thus renamed this effector CvpF for Coxiella vacuolar protein F. CvpF specifically interacts with the host small GTPase RAB26, leading to the recruitment of the autophagosomal marker MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta) to CCVs. Importantly, cvpF::Tn mutants were highly attenuated compared to wild-type bacteria in the SCID mouse model of infection, highlighting the importance of CvpF for Coxiella virulence. These results suggest that CvpF manipulates endosomal trafficking and macroautophagy/autophagy induction for optimal C. burnetii vacuole biogenesis.

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Section: Introductionmentioning

confidence: 99%

Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence

et al. 2020

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“…The environment provided by the lysosome is crucial for metabolic activation of C. burnetii and protein secretion through the Dot/Icm type IV secretion system (T4SS) (223). At least 130 bacterial effector proteins are translocated into the host cell via this T4SS, which collectively modify the CCV and control host behavior to enable C. burnetii replication (224). Multiple effectors perform antiapoptotic functions to keep the host alive, and others act to manipulate autophagy and vesicular traffic to keep the CCV in an autolysosomal state (225)(226)(227).…”

Section: Coxiella Burnetiimentioning

confidence: 99%

Taming the Triskelion: Bacterial Manipulation of Clathrin

Latomanski

Newton

2019

Microbiol Mol Biol Rev

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SUMMARYThe entry of pathogens into nonphagocytic host cells has received much attention in the past three decades, revealing a vast array of strategies employed by bacteria and viruses. A method of internalization that has been extensively studied in the context of viral infections is the use of the clathrin-mediated pathway. More recently, a role for clathrin in the entry of some intracellular bacterial pathogens was discovered. Classically, clathrin-mediated endocytosis was thought to accommodate internalization only of particles smaller than 150 nm; however, this was challenged upon the discovery thatListeria monocytogenesrequires clathrin to enter eukaryotic cells. Now, with discoveries that clathrin is required during other stages of some bacterial infections, another paradigm shift is occurring. There is a more diverse impact of clathrin during infection than previously thought. Much of the recent data describing clathrin utilization in processes such as bacterial attachment, cell-to-cell spread and intracellular growth may be due to newly discovered divergent roles of clathrin in the cell. Not only does clathrin act to facilitate endocytosis from the plasma membrane, but it also participates in budding from endosomes and the Golgi apparatus and in mitosis. Here, the manipulation of clathrin processes by bacterial pathogens, including its traditional role during invasion and alternative ways in which clathrin supports bacterial infection, is discussed. Researching clathrin in the context of bacterial infections will reveal new insights that inform our understanding of host-pathogen interactions and allow researchers to fully appreciate the diverse roles of clathrin in the eukaryotic cell.

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“…Coxiella burnetii is a stealth pathogen that actively escapes innate immune recognition by inhibiting the NF‐κB pathway (Mahapatra et al, ) and inflammasome activation (Cunha et al, ). Infected cells are also protected from apoptosis, thereby preserving the bacterial replicative niche over long periods (Lührmann et al, ). C. burnetii enters macrophages by phagocytosis through the interaction with αVβ3 integrins (Capo et al, ).…”

Section: Introducing Coxiella Burnetiimentioning

confidence: 99%

“…Infected cells are also protected from apoptosis, thereby preserving the bacterial replicative niche over long periods (Lührmann et al, 2017). C. burnetii enters macrophages by phagocytosis through the interaction with αVβ3 integrins (Capo et al, 1999).…”

Section: Introducing Coxiella Burnetiimentioning

confidence: 99%

From neglected to dissected: How technological advances are leading the way to the study ofCoxiella burnetiipathogenesis

Burette

Bonazzi

2020

Cellular Microbiology

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Coxiella burnetii is an obligate intracellular bacterial pathogen responsible for severe worldwide outbreaks of the zoonosis Q fever. The remarkable resistance to environmental stress, extremely low infectious dose and ease of dissemination, contributed to the classification of C. burnetii as a class B biothreat. Unique among intracellular pathogens, C. burnetii escapes immune surveillance and replicates within large autophagolysosome‐like compartments called Coxiella‐containing vacuoles (CCVs). The biogenesis of these compartments depends on the subversion of several host signalling pathways. For years, the obligate intracellular nature of C. burnetii imposed significant experimental obstacles to the study of its pathogenic traits. With the development of an axenic culture medium in 2009, C. burnetii became genetically tractable, thus allowing the implementation of mutagenesis tools and screening approaches to identify its virulence determinants and investigate its complex interaction with host cells. Here, we review the key advances that have contributed to our knowledge of C. burnetii pathogenesis, leading to the rise of this once‐neglected pathogen to an exceptional organism to study the intravacuolar lifestyle.

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Beginning to Understand the Role of the Type IV Secretion System Effector Proteins in Coxiella burnetii Pathogenesis

Cited by 27 publications

References 107 publications

Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence

Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence

Taming the Triskelion: Bacterial Manipulation of Clathrin

From neglected to dissected: How technological advances are leading the way to the study ofCoxiella burnetiipathogenesis

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