title: Multiple leptospiral sphingomyelinases (or are there?).
abstract: Culture supernatants of leptospiral pathogens have long been known to haemolyse erythrocytes. This property is due, at least in part, to sphingomyelinase activity. Indeed, genome sequencing reveals that pathogenic Leptospira species are richly endowed with sphingomyelinase homologues: five genes have been annotated to encode sphingomyelinases in Leptospira interrogans. Such redundancy suggests that this class of genes is likely to benefit leptospiral pathogens in their interactions with the mammalian host. Surprisingly, sequence comparison with bacterial sphingomyelinases for which the crystal structures are known reveals that only one of the leptospiral homologues has the active site amino acid residues required for enzymic activity. Based on studies of other bacterial toxins, we propose that leptospiral sphingomyelinase homologues, irrespective of their catalytic activity, may possess additional molecular functions that benefit the spirochaete. Potential secretion pathways and roles in pathogenesis are discussed, including nutrient acquisition, dissemination, haemorrhage and immune evasion. Although leptospiral sphingomyelinase-like proteins are best known for their cytolytic properties, we believe that a better understanding of their biological role requires the examination of their sublytic properties as well.
authors.affiliation: Department of Animal Sciences, University of Hyderabad, Hyderabad, India.
authors.forename: Suneel A
authors.initials: SA
authors.lastname: Narayanavari
authors.affiliation: Department of Animal Sciences, University of Hyderabad, Hyderabad, India.
authors.forename: Manjula
authors.initials: M
authors.lastname: Sritharan
authors.affiliation: Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.|Department of Urology, University of California at Los Angeles, Los Angeles, CA, USA.|Division of Infectious Diseases, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.|Department of Microbiology, Immunology, and Molecular Genetics, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Haake
authors.affiliation: Research Service, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.|Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Matsunaga
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D002462:Cell Membrane / Q000473:pathology; D007921:Leptospira interrogans / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D007922:Leptospirosis / Q000382:microbiology; D010802:Phylogeny; D013107:Sphingolipids / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D013107:Sphingolipids; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase