A mutation in the mip gene results in an attenuation of Legionella pneumophila virulence.
Infection by Legionella pneumophila is believed to depend upon its ability to multiply within host alveolar macrophages. To investigate this, a site-specific mutation was introduced into a gene (mip) that encodes a 24,000-Da surface protein; an 80-fold loss of infectivity for both U937 cells and explanted human alveolar macrophages was observed. Further phenotypic analysis of the mutant strain has failed to show alterations in bacterial factors (e.g., proteinase, lipopolysaccharide) that have suspected roles in virulence. To substantiate that this mutation also results in reduced virulence in animals, the lethality and clinical illnesses produced by the parent and mutant L. pneumophila strains were compared in guinea pigs after intratracheal inoculation. The mutant strain produced fewer illnesses, slower-progressing disease, and fewer lethal infections than either the parent strain or a derivative of the mutant strain with the wild-type mip gene reintroduced. When sublethal inocula of the three strains were used, the mutant bacteria were recovered in slightly lower numbers from lung homogenates and in significantly lower numbers from the spleen, at 48 h, than were the other two test strains. Thus mip seems to be necessary for full virulence of L. pneumophila and may represent the first genetically defined virulence factor in this species.
Cianciotto
N P
NP
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor 48109.
Eisenstein
B I
BI
Mody
C H
CH
Engleberg
N C
NC
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005798:Genes, Bacterial; D006168:Guinea Pigs; D007875:Legionella / Q000235:genetics / Q000472:pathogenicity*; D007877:Legionnaires' Disease / Q000382:microbiology*; D008168:Lung / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D010586:Phagocytes / Q000382:microbiology; D013154:Spleen / Q000382:microbiology; D014774:Virulence
D001426:Bacterial Proteins; D008565:Membrane Proteins