title: Step-wise loss of bacterial flagellar torsion confers progressive phagocytic evasion.
abstract: Phagocytosis of bacteria by innate immune cells is a primary method of bacterial clearance during infection. However, the mechanisms by which the host cell recognizes bacteria and consequentially initiates phagocytosis are largely unclear. Previous studies of the bacterium Pseudomonas aeruginosa have indicated that bacterial flagella and flagellar motility play an important role in colonization of the host and, importantly, that loss of flagellar motility enables phagocytic evasion. Here we use molecular, cellular, and genetic methods to provide the first formal evidence that phagocytic cells recognize bacterial motility rather than flagella and initiate phagocytosis in response to this motility. We demonstrate that deletion of genes coding for the flagellar stator complex, which results in non-swimming bacteria that retain an initial flagellar structure, confers resistance to phagocytic binding and ingestion in several species of the gamma proteobacterial group of Gram-negative bacteria, indicative of a shared strategy for phagocytic evasion. Furthermore, we show for the first time that susceptibility to phagocytosis in swimming bacteria is proportional to mot gene function and, consequently, flagellar rotation since complementary genetically- and biochemically-modulated incremental decreases in flagellar motility result in corresponding and proportional phagocytic evasion. These findings identify that phagocytic cells respond to flagellar movement, which represents a novel mechanism for non-opsonized phagocytic recognition of pathogenic bacteria.
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, New Hampshire, United States of America.
authors.forename: Rustin R
authors.initials: RR
authors.lastname: Lovewell
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Collins
authors.forename: Julie L
authors.initials: JL
authors.lastname: Acker
authors.forename: George A
authors.initials: GA
authors.lastname: O'Toole
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wargo
authors.forename: Brent
authors.initials: B
authors.lastname: Berwin
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005407:Flagella / Q000276:immunology / Q000502:physiology*; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009068:Movement; D010587:Phagocytosis; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D054159:Torsion, Mechanical
chemical_list: D001426:Bacterial Proteins; C063010:MotA protein, Bacteria