Mutations affecting Leptospira interrogans lipopolysaccharide attenuate virulence

Leptospira interrogans is the causative agent of leptospirosis. Lipopolysaccharide (LPS) is the major outer membrane component of L. interrogans. It is the dominant antigen recognized during infection and the basis for serological classification. The structure of LPS and its role in pathogenesis are...

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Bibliographic Details
Published in:Molecular microbiology 2010-11, Vol.78 (3), p.701-709
Main Authors: Murray, Gerald L, Srikram, Amporn, Henry, Rebekah, Hartskeerl, Rudy A, Sermswan, Rasana W, Adler, Ben
Format: Article
Language:English
Subjects:
Animals
Bacteria
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacteriology
Biological and medical sciences
Cricetinae
Fundamental and applied biological sciences. Psychology
Humans
Leptospira interrogans
Leptospira interrogans - genetics
Leptospira interrogans - metabolism
Leptospira interrogans - pathogenicity
Leptospirosis - microbiology
Lipopolysaccharides - deficiency
Lipopolysaccharides - genetics
Membranes
Mesocricetus
Microbiology
Miscellaneous
Molecular biology
Mutagenesis, Insertional
Mutation
Pathogenesis
Proteins
Virulence
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Summary:Leptospira interrogans is the causative agent of leptospirosis. Lipopolysaccharide (LPS) is the major outer membrane component of L. interrogans. It is the dominant antigen recognized during infection and the basis for serological classification. The structure of LPS and its role in pathogenesis are unknown. We describe two defined mutants of L. interrogans serovar Manilae with transposon insertions in the LPS locus. Mutant M895 was disrupted in gene la1641 encoding a protein with no known homologues. M1352 was disrupted in a gene unique to serovar Manilae also encoding a protein of unknown function. M895 produced truncated LPS while M1352 showed little or no change in LPS molecular mass. Both mutants showed altered agglutination titres against rabbit antiserum and against a panel of LPS‐specific monoclonal antibodies. The mutants were severely attenuated in virulence via the intraperitoneal route of infection, and were cleared from the host animal by 3 days after infection. M895 was also highly attenuated via the mucosal infection route. Resistance to complement in human serum was unaltered for both mutants. While complementation of mutants was not possible, the attenuation of two independently derived LPS mutants demonstrates for the first time that LPS plays an essential role leptospiral virulence.
ISSN:0950-382X
1365-2958
DOI:10.1111/j.1365-2958.2010.07360.x