Yersinia pestis Requires Host Rab1b for Survival in Macrophages.
Yersinia pestis is a facultative intracellular pathogen that causes the disease known as plague. During infection of macrophages Y. pestis actively evades the normal phagosomal maturation pathway to establish a replicative niche within the cell. However, the mechanisms used by Y. pestis to subvert killing by the macrophage are unknown. Host Rab GTPases are central mediators of vesicular trafficking and are commonly targeted by bacterial pathogens to alter phagosome maturation and killing by macrophages. Here we demonstrate for the first time that host Rab1b is required for Y. pestis to effectively evade killing by macrophages. We also show that Rab1b is specifically recruited to the Yersinia containing vacuole (YCV) and that Y. pestis is unable to subvert YCV acidification when Rab1b expression is knocked down in macrophages. Furthermore, Rab1b knockdown also altered the frequency of association between the YCV with the lysosomal marker Lamp1, suggesting that Rab1b recruitment to the YCV directly inhibits phagosome maturation. Finally, we show that Rab1b knockdown also impacts the pH of the Legionella pneumophila containing vacuole, another pathogen that recruits Rab1b to its vacuole. Together these data identify a novel role for Rab1b in the subversion of phagosome maturation by intracellular pathogens and suggest that recruitment of Rab1b to the pathogen containing vacuole may be a conserved mechanism to control vacuole pH.
Department of Microbiology and Immunology and the Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.
Michael G
MG
Connor
Department of Microbiology and Immunology and the Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.
Amanda R
AR
Pulsifer
Department of Microbiology and Immunology and the Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.
Christopher T
CT
Price
Department of Microbiology and Immunology and the Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.
Yousef
Y
Abu Kwaik
Department of Microbiology and Immunology and the Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville School of Medicine, Louisville, Kentucky, United States of America.
Matthew B
MB
Lawrenz
D006801:Humans; D006863:Hydrogen-Ion Concentration; D016952:Legionella pneumophila / Q000502:physiology; D008247:Lysosomes / Q000502:physiology; D008264:Macrophages / Q000382:microbiology*; D008869:Microtubule-Associated Proteins / Q000502:physiology; D010588:Phagosomes / Q000502:physiology; D014617:Vacuoles / Q000382:microbiology / Q000502:physiology; D015010:Yersinia pestis / Q000502:physiology*; D020761:rab1 GTP-Binding Proteins / Q000502:physiology*
C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C529587:Rab1B protein, human; D020761:rab1 GTP-Binding Proteins