Major surface protein LipL32 is not required for either acute or chronic infection with Leptospira interrogans.
Leptospira interrogans is responsible for leptospirosis, a zoonosis of worldwide distribution. LipL32 is the major outer membrane protein of pathogenic leptospires, accounting for up to 75% of total outer membrane protein. In recent times LipL32 has become the focus of intense study because of its surface location, dominance in the host immune response, and conservation among pathogenic species. In this study, an lipL32 mutant was constructed in L. interrogans using transposon mutagenesis. The lipL32 mutant had normal morphology and growth rate compared to the wild type and was equally adherent to extracellular matrix. Protein composition of the cell membranes was found to be largely unaffected by the loss of LipL32, with no obvious compensatory increase in other proteins. Microarray studies found no obvious stress response or upregulation of genes that may compensate for the loss of LipL32 but did suggest an association between LipL32 and the synthesis of heme and vitamin B(12). When hamsters were inoculated by systemic and mucosal routes, the mutant caused acute severe disease manifestations that were indistinguishable from wild-type L. interrogans infection. In the rat model of chronic infection, the LipL32 mutant colonized the renal tubules as efficiently as the wild-type strain. In conclusion, this study showed that LipL32 does not play a role in either the acute or chronic models of infection. Considering the abundance and conservation of LipL32 among all pathogenic Leptospira spp. and its absence in saprophytic Leptospira, this finding is remarkable. The role of this protein in leptospiral biology and pathogenesis thus remains elusive.
Murray
Gerald L
GL
Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Srikram
Amporn
A
Hoke
David E
DE
Wunder
Elsio A
EA
Henry
Rebekah
R
Lo
Miranda
M
Zhang
Kunkun
K
Sermswan
Rasana W
RW
Ko
Albert I
AI
Adler
Ben
B
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006224:Cricetinae; D007921:Leptospira interrogans / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D007922:Leptospirosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D008647:Mesocricetus; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar
D001425:Bacterial Outer Membrane Proteins; C406589:LipL32 protein, Leptospira; D008074:Lipoproteins