Disease relevance of Leptospira

• After the spirochete had been isolated, its distinctness from other North American tick-borne borreliae as well as from Spirochaeta aurantia, Treponema pallidum, and Leptospira interrogans serovar pomona was established on the basis of its morphology, protein components, and inability to infect mice [1].
• To elucidate the role of leptospira outer membrane proteins in tubulointerstitial nephritis, outer membrane proteins from pathogenic Leptospira shermani and nonpathogenic Leptospira patoc extracted by Triton X-114 were administered to cultured mouse proximal tubule cells [2].
• Detection of Leptospira DNA by polymerase chain reaction in aqueous humor of a patient with unilateral uveitis [3].
• Cloning of a gene required for tryptophan biosynthesis from Leptospira biflexa serovar patoc into Escherichia coli [4].
• These monoclonal antibodies did not react with nonpathogenic treponemes, such as T. phagedenis Reiter, T. denticola MRB, T. refringens Noguchi, or other spirochetes, such as Borrelia burgdorferi and Leptospira interrogans serovar pomona in microimmunofluorescent antibody smear slides or in Western blots (immunoblots) [5].

High impact information on Leptospira

• Movement of antibody-coated latex beads attached to the spirochete Leptospira interrogans [6].
• A Leptospira interrogans enzyme with similarity to yeast Ste14p that methylates the 1-phosphate group of lipid A [7].
• This arrangement is similar to that of Leptospira interrogans PDF, the only other dimeric PDF identified to date [8].
• A methylated phosphate group and four amide-linked acyl chains in leptospira interrogans lipid A. The membrane anchor of an unusual lipopolysaccharide that activates TLR2 [9].
• We now demonstrate that LpxA in cell extracts of Mesorhizobium loti and Leptospira interrogans, which synthesize lipid A molecules containing 2,3-diamino-2,3-dideoxy-d-glucopyranose (GlcN3N) units in place of glucosamine, do not acylate UDP-GlcNAc [10].

Chemical compound and disease context of Leptospira

• Antibody-coated latex beads (Ab-beads) were attached to Leptospira interrogans serovars illini 3055 and icterohaemorrhagiae SC1157 [6].
• Two stereocontrolled syntheses of a methyl glycoside of an alternating beta-(1-->4)-beta-(1-->3)-mannohexaose, representative of the mannan from Rhodotorula glutinis, Rhodotorula mucilaginosa, and Leptospira biflexa, are described [11].
• The third enzyme investigated was O-acetylhomoserine (OAH) sulfhydrylase of Leptospira meyeri, representing the enzyme that utilizes OAH and operates through the direct sulfhydrylation pathway [12].
• Susceptibility of mice treated with cyclophosphamide to lethal infection with Leptospira interrogans Serovar pomona [13].
• A broader application of these two techniques included 12 serovars (including seven species) of Leptospira and six antimicrobials (penicillin G, doxycycline, chloramphenicol, erythromycin, cefotaxime, and ciprofloxacin) [14].

Biological context of Leptospira

• In this study we show that in vitro exposure of naive human PBMC to Leptospira interrogans results in cell proliferation and the production of IFN-gamma, IL-12, and TNF-alpha [15].
• Nucleotide sequence analysis of a gene cloned from Leptospira biflexa serovar patoc which complements an argE defect in Escherichia coli [16].
• By using the same methodology, the cloned recA of Leptospira biflexa was interrupted by a kanamycin resistance cassette, and the mutated allele was then introduced into the L. biflexa chromosome by homologous recombination [17].
• Analysis of the G+C content, DNA-DNA relatedness to other leptospires and 16S rRNA gene sequence of Leptospira parva showed that this species was not related to other Leptospira species [18].
• Hamsters were immunised with leptospiral lipopolysaccharide (LPS) or the polysaccharide (PS) fraction of LPS from Leptospira interrogans serovar copenhageni and the antibody responses were measured by agglutination tests [19].

Anatomical context of Leptospira

• Macrophages from C3H/HeJ, TLR4-/-, and MyD88-/- mice secreted far-lower levels of cytokines than wild-type macrophages in response to Leptospira [20].
• Peritoneal macrophages from CD14-/- and TLR2-/- mice exhibited no defect in cytokine responses to Leptospira compared to controls [20].
• Hybridomas secreting specific monoclonal antibodies (MAb) to all members of the genus Leptospira (clone LF9) and those that are specific only to the pathogenic species (clones LD5 and LE1) were produced [21].
• Moreover, sera from patients with leptospirosis also recognized the recombinant HlyX, showing that it is presented to the host immune system during Leptospira infection [22].
• The diaminopimelic acid present in cell wall peptidoglycans of the genus Leptospira was meso-diaminopimelic acid (A2pm) [23].

Gene context of Leptospira

• Leptospira outer membrane protein activates NF-kappaB and downstream genes expressed in medullary thick ascending limb cells [24].
• Leptospira biflexa allelic exchange mutants containing an inactivated hemH gene were recovered only when exogenous haemin was present [25].
• Toll-like receptor 4 protects against lethal Leptospira interrogans serovar icterohaemorrhagiae infection and contributes to in vivo control of leptospiral burden [20].
• Three leuA-like protein-coding sequences were identified in Leptospira interrogans [26].
• This is the first molecular study on hslV and hslU in a Leptospira species [27].

Analytical, diagnostic and therapeutic context of Leptospira

• In the present study, N-terminal sequencing of a 32-kDa fraction and Southern blotting of genomic DNA with corresponding degenerated oligonucleotide probes identified two of its constituents: hemolysis-associated protein 1 (Hap1) and the outer membrane Leptospira protein 1 (OmpL1) [28].
• Adenovirus-mediated Hap1 vaccination induces significant protection against a virulent heterologous Leptospira challenge in gerbils, whereas a similar OmpL1 construct failed to protect the animals [28].
• The surfaceome of Leptospira was investigated by biotin labeling of viable leptospires, affinity capture of the biotinylated proteins, two-dimensional gel electrophoresis, and mass spectrometry (MS) [29].
• Radioimmunoassay system using a serovar-specific lipopolysaccharide antigen of Leptospira [30].
• Cloning, high-level expression, purification and crystallization of peptide deformylase from Leptospira interrogans [31].

References