Components of the Legionella pneumophila flagellar regulon contribute to multiple virulence traits, including lysosome avoidance and macrophage death.
Legionella pneumophila is a motile intracellular pathogen of macrophages and amoebae. When nutrients become scarce, the bacterium induces expression of transmission traits, some of which are dependent on the flagellar sigma factor FliA (sigma(28)). To test how particular components of the L. pneumophila flagellar regulon contribute to virulence, we compared a fliA mutant with strains whose flagellar construction is disrupted at various stages. We find that L. pneumophila requires FliA to avoid lysosomal degradation in murine bone marrow-derived macrophages (BMM), to regulate production of a melanin-like pigment, and to regulate binding to the dye crystal violet, whereas motility, flagellar secretion, and external flagella or flagellin are dispensable for these activities. Thus, in addition to flagellar genes, the FliA sigma factor regulates an effector(s) or regulator(s) that contributes to other transmissive traits, notably inhibition of phagosome maturation. Whether or not the microbes produced flagellin, all nonmotile L. pneumophila mutants bound BMM less efficiently than the wild type, resulting in poor infectivity and a loss of contact-dependent death of BMM. Therefore, bacterial motility increases contact with host cells during infection, but flagellin is not an adhesin. When BMM contact by each nonmotile strain was promoted by centrifugation, all the mutants bound BMM similarly, but only those microbes that synthesized flagellin induced BMM death. Thus, the flagellar regulon equips the aquatic pathogen L. pneumophila to coordinate motility with multiple traits vital to virulence.
Molofsky
A B
AB
Department of Microbiology and Immunology, University of Michigan Medical School, 6734 Medical Sciences Building II, Ann Arbor, MI 48109-0620, USA.
Shetron-Rama
L M
LM
Swanson
Michele S
MS
D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D016923:Cell Death; D002478:Cells, Cultured; D005260:Female; D005407:Flagella / Q000502:physiology*; D005408:Flagellin / Q000378:metabolism; D006358:Hot Temperature; D016952:Legionella pneumophila / Q000201:enzymology* / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007877:Legionnaires' Disease; D008264:Macrophages / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D009113:Muramidase / Q000502:physiology*; D018085:Regulon / Q000502:physiology*; D012808:Sigma Factor / Q000502:physiology; D012964:Sodium / Q000494:pharmacology; D014774:Virulence
D001426:Bacterial Proteins; C064971:FliA protein, Bacteria; D012808:Sigma Factor; D005408:Flagellin; D012964:Sodium; D009113:Muramidase