Immunodominant antigens recognized by the human immune response to infection by organisms of the species Leptospira interrogans serogroup Australis

Cinco, M

doi:10.1016/0378-1097(92)90009-d

Cited by 6 publications

(7 citation statements)

References 24 publications

(49 reference statements)

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“…L. interrogans LPS is also an immunodominant molecule (26,27) and is unique in that it is recognized by Toll-like receptor 2 (TLR2) and not TLR4 in human cells (LPS from the majority of other Gram-negative bacteria is recognized by TLR4) (28). Pathogenic Leptospira strains demonstrate more abundant and longer LPS than the saprophyte Leptospira biflexa (29), and mutations affecting the native biosynthesis of LPS affect both virulence in hamsters (30) and colonization of target organs in the mouse model (31).…”

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confidence: 99%

Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence

et al. 2015

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Leptospirosis is an emerging disease with an annual occurrence of over 1 million human cases worldwide. Pathogenic Leptospira bacteria are maintained in zoonotic cycles involving a diverse array of mammals, with the capacity to survive outside the host in aquatic environments. Survival in the diverse environments encountered by Leptospira likely requires various adaptive mechanisms. Little is known about Leptospira outer membrane modification systems, which may contribute to the capacity of these bacteria to successfully inhabit and colonize diverse environments and animal hosts. Leptospira bacteria carry two genes annotated as UDP-3-O-[3-hydroxymyristoyl] glucosamine N-acyltransferase genes (la0512 and la4326 [lpxD1 and lpxD2]) that in other bacteria are involved in the early steps of biosynthesis of lipid A, the membrane lipid anchor of lipopolysaccharide. Inactivation of only one of these genes, la0512/lpxD1, imparted sensitivity to the host physiological temperature (37°C) and rendered the bacteria avirulent in an animal infection model. Polymyxin B sensitivity assays revealed compromised outer membrane integrity in the lpxD1 mutant at host physiological temperature, but structural analysis of lipid A in the mutant revealed only minor changes in the lipid A moiety compared to that found in the wild-type strain. In accordance with this, an in trans complementation restored the phenotypes to a level comparable to that of the wild-type strain. These results suggest that the gene annotated as lpxD1 in Leptospira interrogans plays an important role in temperature adaptation and virulence in the animal infection model. Members of the genus Leptospira are spirochete bacteria encompassing saprophytic and pathogenic species and are considered to be the most widespread zoonotic bacteria worldwide (1). Leptospira is the etiological agent of the disease leptospirosis, which in severe manifestations leads to hemorrhage in the lungs, meningitis, and liver and/or kidney failure (1). Leptospirosis is an emerging disease, and the worldwide annual occurrence is estimated to be over 1 million human cases, with a 5 to 20% mortality rate (2, 3). Leptospira cannot breach the host epidermal lining, and transmission requires direct contact of the bacteria with cuts or abrasions in the skin (4, 5). Rats and other rodent species serve as reservoir hosts for Leptospira, which colonizes the urinary systems of these animals (6). Leptospira is shed back into the environment through the urine of reservoir hosts and can persist in freshwater and soil until direct contact with an animal recommences an infection cycle (7,8).A prominent Leptospira feature is the ability to proliferate under significantly different environmental conditions. Other Gram-negative bacterial pathogens with this ability include species of the genera Escherichia (9), Salmonella (10), Yersinia (11), Vibrio (12), and Pseudomonas (13). The capacity of bacteria to adapt to disparate environments is likely imparted by numerous evolved strategies that probably include modi...

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confidence: 99%

Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence

et al. 2015

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“…Furthermore, leptospiral LPS elicits the production of agglutinating, opsonic, protective antibodies in mice, hamsters and humans [2^4]. Even though a protective role for OmpL1 and LipL41 outer membrane proteins in leptospirosis has been reported [5], LPS is considered the main protective antigen identi¢ed thus far in leptospires [6]. There are no data describing the structure of the LPS of Leptospira that would explain the serological diversity in this species.…”

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confidence: 99%

Genetic differences among the LPS biosynthetic loci of serovars of Leptospira interrogans and Leptospira borgpetersenii

Peña-Moctezuma¹

2001

FEMS Immunology and Medical Microbiology

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The gene organization in the lipopolysaccharide biosynthetic (rfb) locus was analyzed in seven Leptospira interrogans serovars within serogroup Icterohemorrhagiae, seven non-Icterohemorrhagiae serovars and one Leptospira borgpetersenii serovar. Two groups of loci were delineated based on DNA hybridization and sequence analysis. Group 1 contained the two Hardjo subtypes, Hardjoprajitno and Hardjobovis. Group 2 (containing Copenhageni, Pomona, Naam, Mwogolo, Smithi, Lai, Canicola, Autumnalis, Pyrogenes, Australis and Icterohemorrhagiae) differed from Group 1 in its organization upstream of orf11, where five ORFs (32, 33, 34, 35, 37) were identified that were not contained in the Group 1 loci. These ORFs encoded a putative epimerase (orf32), a glycosyltransferase (orf33), two integral membrane proteins (orfs 34 and 35), and a galactosyltransferase (orf37). Serovars Australis, Pomona and Autumnalis did not contain orf37. Serovar Bataviae was excluded from the grouping because of its unique genetic organization upstream of orf13. In the Group 2 loci, comparison of the genetic layout at the 5' end revealed differences which included mutations disrupting reading frames in either or both orf34 and orf35 and apparent allelic differences between orf33 homologs that may be sufficient to account for the genetic basis of serovar identity.

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“…The serovar-based classi¢cation of Leptospira depends on the diversity of structure of the surface-exposed components of lipopolysaccharide (LPS). Notably, LPS is the only protective antigen identi¢ed thus far [5]. Furthermore, leptospiral LPS elicits the production of agglutinating, opsonic, protective antibodies in mice and hamsters [6,7].…”

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confidence: 99%

Comparative analysis of the LPS biosynthetic loci of the genetic subtypes of serovar Hardjo: Leptospira interrogans subtype Hardjoprajitno and Leptospira borgpetersenii subtype Hardjobovis

Peña-Moctezuma¹

1999

FEMS Microbiology Letters

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Although Leptospira borgpetersenii subtype Hardjobovis and L. interrogans subtype Hardjoprajitno belong to different species, they are serologically indistinguishable and are therefore classified as serovar Hardjo. Since LPS is the major antigen involved in serological classification, this implies that the LPS of these subtypes is identical. Comparison of the LPS biosynthetic loci (rfb) of the subtypes revealed remarkable similarity, with 32 and 31 origins of replication (orfs) in the Hardjoprajitno and Hardjobovis rfb loci, respectively. The order and orientation of these orfs were identical with the exception of an additional orf in Hardjoprajitno between orfs 4 and 5 and intergenic sequences differing between the subtypes. The Hardjoprajitno rfb locus has been divided into four intercalated regions based on sequence similarity to other leptospiral rfb loci. orfJ1-orfJ14 as well as orfJ21-orfJ22 are more similar to regions of the rfb locus of L. borgpetersenii subtype Hardjobovis. orfJ15-orfJ20 as well as orfJ23-orfJ31 are almost identical to the corresponding orfs in L. interrogans serovar Copenhageni. We propose that the progenitor Hardjoprajitno strain, containing an rfb locus which closely resembled the Copenhageni locus, acquired orfs 1-14 and orfs 21-22 from subtype Hardjobovis resulting in two serologically indistinguishable subtypes of serovar Hardjo which in turn constituted the main bovine-adapted leptospiral serovar.

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Immunodominant antigens recognized by the human immune response to infection by organisms of the species Leptospira interrogans serogroup Australis

Cited by 6 publications

References 24 publications

Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence

Leptospira interrogans lpxD Homologue Is Required for Thermal Acclimatization and Virulence

Genetic differences among the LPS biosynthetic loci of serovars of Leptospira interrogans and Leptospira borgpetersenii

Comparative analysis of the LPS biosynthetic loci of the genetic subtypes of serovar Hardjo: Leptospira interrogans subtype Hardjoprajitno and Leptospira borgpetersenii subtype Hardjobovis

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