Coxiella effector protein CvpF subverts RAB26-dependent autophagy to promote vacuole biogenesis and virulence.
Fernande Ayenoue Siadous,Franck Cantet,Erin J. van Schaik,Melanie Burette,Julie Allombert,Anissa Lakhani,Boris Bonaventure,Caroline Goujon,James E. Samuel,Matteo Bonazzi,Eric Martinez +10 more
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TLDR
It is demonstrated 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 Coxieella-containing vacuoles (CCVs).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 Coxiella-containing 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.Abbreviations: ACCM: acidified citrate cystein medium; AP: adaptor related protein complex; CCV: Coxiella-containing vacuole; Cvp: Coxiella vacuolar protein; GDI: guanosine nucleotide dissociation inhibitor; GDF: GDI dissociation factor; GEF: guanine exchange factor; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MTORC1: mechanistic target of rapamycin kinase MTOR complex 1; PBS: phosphate-buffered saline; PMA: phorbol myristate acetate; SQSTM1/p62: sequestosome 1; WT: wild-type.read more
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circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway
Wei Gao,Guo Huina,Min Niu,Zheng Xiwang,Yuliang Zhang,Xue Xuting,Yunfeng Bo,Guan Xiaoya,Li Zhongxun,Yujia Guo,Long He,Yu Zhang,Li Li,Jimin Cao,Yongyan Wu +14 more
TL;DR: This study reveals that the novel autophagy-suppressive circPARD3 promotes LSCC progression and chemoresistance through the PRKCI-Akt-mTOR pathway, providing new insights into circRNA-mediated autophagic regulation and potential biomarker and target for LSCC treatment.
Journal ArticleDOI
Interfering with Autophagy: The Opposing Strategies Deployed by Legionella pneumophila and Coxiella burnetii Effector Proteins.
TL;DR: The effector proteins that Legionella pneumophila and Coxiella burnetii utilize to modulate the host autophagy pathway in order to survive and replicate are explored.
Journal ArticleDOI
Modulation of innate immune signaling by a Coxiella burnetii eukaryotic-like effector protein
Melanie Burette,Julie Allombert,Karine Lambou,Ghizlane Maarifi,Sébastien Nisole,Elizabeth Di Russo Case,Fabien Blanchet,Cedric Hassen-Khodja,Stéphanie Cabantous,James E. Samuel,Eric Martinez,Matteo Bonazzi +11 more
TL;DR: A new effector protein, NopA (nucleolar protein A), is discovered, which localizes at nucleoli of infected cells and perturbs nucleocytoplasmic transport by manipulating the intracellular gradients of the GTPase Ran, and is an important regulator of the innate immune response allowing Coxiella to behave as a stealth pathogen.
Journal ArticleDOI
Autophagy-A Story of Bacteria Interfering with the Host Cell Degradation Machinery.
TL;DR: A review of autophagy as a response to intracellular pathogens can be found in this paper, where the authors discuss recent findings on autophagous reactions to various types of pathogens such as Salmonella typhimurium, Listeria monocytogenes, Mycobacterium tuberculosis, Staphylococcus aureus, and pathogenic Escherichia coli.
Journal ArticleDOI
The secreted protein kinase CstK from Coxiella burnetii influences vacuole development and interacts with the GTPase-activating host protein TBC1D5
Eric Martinez,Sylvaine Huc-Brandt,Solène Brelle,Julie Allombert,Franck Cantet,Laila Gannoun-Zaki,Melanie Burette,Marianne Martin,François Letourneur,Matteo Bonazzi,Virginie Molle +10 more
TL;DR: The results indicate that CstK functions as a bacterial effector protein that interacts with the host protein TBC1D5 during vacuole biogenesis and intracellular replication.
References
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Journal ArticleDOI
Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii.
Daniel E. Voth,Robert A. Heinzen +1 more
TL;DR: Current understanding of the cellular events that occur during parasitism of host cells by Coxiella, including deployment of a type IV secretion system to deliver effector proteins to the host cytosol is summarized.
Journal ArticleDOI
Dynein-dependent movement of autophagosomes mediates efficient encounters with lysosomes.
TL;DR: The real-time behavior of microtubule-associated protein light chain 3 (LC3), which localizes to autophagosomes, is observed, and it is shown that autphagosomes move in a micro Tubule- and dynein-dynactin motor complex-dependent manner.
Journal ArticleDOI
Regulation of autophagy by the Rab GTPase network
X Ao,L Zou,Yuanyuan Wu +2 more
TL;DR: New findings regarding the involvement of Rabs in autophagy are summarized and insights regarding future research on the mechanisms of autophagic regulation are provided.
Journal ArticleDOI
Autophagy induction favours the generation and maturation of the Coxiella‐replicative vacuoles
Maximiliano G. Gutierrez,Cristina Lourdes Vázquez,Daniela B. Munafó,Felipe Carlos Martín Zoppino,Walter Berón,Michel Rabinovitch,María Isabel Colombo +6 more
TL;DR: The results suggest that transit through the autophagic pathway increases the infection with Coxiella by providing a niche more favourable to their initial survival and multiplication.
Journal ArticleDOI
The autophagic pathway is actively modulated by phase II Coxiella burnetii to efficiently replicate in the host cell.
Patricia Silvia Romano,Maximiliano G. Gutierrez,Walter Berón,Michel Rabinovitch,María Isabel Colombo +4 more
TL;DR: It is proposed that C.’burnetii transits through the normal endo/phagocytic pathway but actively interacts with autophagosomes at early times after infection, possibly favouring the intracellular differentiation and survival of the bacteria.