title: Mycobacterium tuberculosis lipoprotein LprG binds lipoarabinomannan and determines its cell envelope localization to control phagolysosomal fusion.
abstract: Mycobacterium tuberculosis (Mtb) virulence is decreased by genetic deletion of the lipoprotein LprG, but the function of LprG remains unclear. We report that LprG expressed in Mtb binds to lipoglycans, such as lipoarabinomannan (LAM), that mediate Mtb immune evasion. Lipoglycan binding to LprG was dependent on both insertion of lipoglycan acyl chains into a hydrophobic pocket on LprG and a novel contribution of lipoglycan polysaccharide components outside of this pocket. An lprG null mutant (Mtb ΔlprG) had lower levels of surface-exposed LAM, revealing a novel role for LprG in determining the distribution of components in the Mtb cell envelope. Furthermore, this mutant failed to inhibit phagosome-lysosome fusion, an immune evasion strategy mediated by LAM. We propose that LprG binding to LAM facilitates its transfer from the plasma membrane into the cell envelope, increasing surface-exposed LAM, enhancing cell envelope integrity, allowing inhibition of phagosome-lysosome fusion and enhancing Mtb survival in macrophages.
authors.affiliation: Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Supriya
authors.initials: S
authors.lastname: Shukla
authors.affiliation: Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Richardson
authors.affiliation: Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Jaffre J
authors.initials: JJ
authors.lastname: Athman
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: Libin
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Wearsch
authors.affiliation: Center for AIDS Research, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Department of Molecular Biology and Microbiology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: McDonald
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Palo Alto, California, United States of America.
authors.forename: Niaz
authors.initials: N
authors.lastname: Banaei
authors.affiliation: Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Center for AIDS Research, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Division of Infectious Diseases, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Palo Alto, California, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Jackson
authors.affiliation: Department of Pathology, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Center for AIDS Research, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Division of Infectious Diseases, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D008070:Lipopolysaccharides / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D008561:Membrane Fusion; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D010588:Phagosomes / Q000378:metabolism*; D014376:Tuberculosis / Q000382:microbiology*; D014774:Virulence
chemical_list: D008070:Lipopolysaccharides; D008074:Lipoproteins; C050016:lipoarabinomannan