Publications

doxycycline attenuates leptospira-induced il-1β by suppressing nlrp3 inflammasome priming.	doxycycline (dox), a semisynthetic antibiotic, has been reported to exert multiple immunomodulatory effects. treatment with dox has a satisfactory curative effect against leptospirosis. in addition to its antibacterial action, we supposed that dox also modulated immune response in controlling leptospira infection. using j774a.1 mouse macrophages, the effects of dox on protein and mrna levels of il-1β and tnf-α were investigated after infection with live or sonicated leptospira interrogans serova ...	2017	28791016
structural and mutational analyses of the leptospira interrogans virulence-related heme oxygenase provide insights into its catalytic mechanism.	heme oxygenase from leptospira interrogans is an important virulence factor. during catalysis, redox equivalents are provided to this enzyme by the plastidic-type ferredoxin-nadp+ reductase also found in l. interrogans. this process may have evolved to aid this bacterial pathogen to obtain heme-iron from their host and enable successful colonization. herein we report the crystal structure of the heme oxygenase-heme complex at 1.73 å resolution. the structure reveals several distinctive features ...	2017	28771589
a new model of self-resolving leptospirosis in mice infected with a strain of leptospira interrogans serovar autumnalis harboring lps signaling only through tlr4.	leptospirosis is an emerging worldwide zoonosis caused by pathogenic leptospira spp. our understanding of leptospirosis pathogenesis and host immune response remains limited, while mechanistic studies are hindered by a lack of proper animal models and immunological reagents. here we established a murine model of acute and self-resolving leptospirosis by infecting 10-week-old c57bl/6 mice with leptospira interrogans serovar autumnalis strain 56606v, with characteristic manifestations including ja ...	2017	28536433
pressor support during a jarisch herxheimer reaction after initiation of treatment for weil's disease.	we present a case of weil's disease complicated by a jarisch-herxheimer reaction (jhr) after initiation of antibiotics while in the emergency department requiring invasive monitoring and vasopressor support. the case is followed by a brief review of the jhr which is rarely observed with treatment of leptospirosis. a healthy 28-year-old female who recently returned from the caribbean presented to the emergency department with flu-like symptoms. the patient appeared jaundiced with conjunctival suf ...	2017	28527874
discovery of novel leptospirosis vaccine candidates using reverse and structural vaccinology.	leptospira spp. are diderm (two membranes) bacteria that infect mammals causing leptospirosis, a public health problem with global implications. thousands of people die every year due to leptospirosis, especially in developing countries with tropical climates. prophylaxis is difficult due to multiple factors, including the large number of asymptomatic hosts that transmit the bacteria, poor sanitation, increasing numbers of slum dwellers, and the lack of an effective vaccine. several leptospiral ...	2017	28496441
lethal pulmonary hemorrhage syndrome due to leptospira infection transmitted by pet rat.	human infection with leptospira interrogans can be life-threatening. multiple organ involvement frequently presents with liver and kidney failure, less commonly including severe hemolysis and pulmonary hemorrhage syndrome. here, we present a fulminant case of leptospirosis presenting with hemolysis and pulmonary hemorrhage. a formerly healthy 34 year old patient presented to a rural hospital with dyspnea and hemoptysis after a week of influenza-like symptoms. initial assessment revealed severe s ...	2017	28491815
comparison between generalized linear modelling and additive bayesian network; identification of factors associated with the incidence of antibodies against leptospira interrogans sv pomona in meat workers in new zealand.	additive bayesian network (abn) is a graphical model which extends generalized linear modelling (glm) to multiple dependent variables. the present study compares results from glm with those from abn analysis used to identify factors associated with leptospira interrogans sv pomona (pomona) infection by exploring the advantages and disadvantages of these two methodologies, to corroborate inferences informing health and safety measures at abattoirs in new zealand (nz).	2017	28487178
leptospira species in feral cats and black rats from western australia and christmas island.	leptospirosis is a neglected, re-emerging bacterial disease with both zoonotic and conservation implications. rats and livestock are considered the usual sources of human infection, but all mammalian species are capable of carrying leptospira spp. and transmitting pathogenic leptospires in their urine, and uncertainty remains about the ecology and transmission dynamics of leptospira in different regions. in light of a recent case of human leptospirosis on tropical christmas island, this study ai ...	2017	28437186
anti-erythrocyte igg in hamsters with acute experimental infection by leptospira interrogans serovar canicola.	the aim of this study was to evaluate the behavior of erythrocyte and platelet, as immunological markers, as well as evaluate the involvement of these factors in hemolytic and hemorrhagic reactions in hamsters experimentally infected by leptospira interrogans serovar canicola. our experimental design was composed by two randomized groups: infected group (ig) (n = 12) and control group (cg) (n = 6). ninety-six hours after the inoculation, the presence of immunoglobulins (igg and igm) and compleme ...	2017	28648625
beyond rabies: are free-ranging skunks (mephitis mephitis) in british columbia reservoirs of emerging infection?	wild animal reservoirs are an important source of emerging and zoonotic infection. skunks (mephitis mephitis) are a reservoir of skunk strain rabies virus in canada, with the exception of some areas including the province of british columbia (bc). beyond rabies, the reservoir status of skunks for emerging and zoonotic pathogens in bc is unknown. from march 2011 to february 2015, 50 free-ranging skunks were necropsied and tested for 4 pathogens: influenza a, aleutian disease virus (adv), leptospi ...	2017	26392297
evidence of leptospirosis in the kidneys and serum of feral swine (sus scrofa) in the united states.	leptospirosis is the most widespread zoonosis in humans worldwide. in the united states, widespread detection of antibodies to leptospirosis have been identified in feral swine (sus scrofa) with the highest detection of serovars, bratislava, icterohaemorrhagiae, and pomona. over the past few years, feral swine populations have expanded their geographical range and distribution in the united states with reports in at least 39 of 50 states. since feral swine serve as reservoirs for serovars that c ...	2017	27697080
evidence for wild crocodiles as a risk for human leptospirosis, mexico.	sentinel species such as crocodilians are used to monitor the health of ecosystems. however, few studies have documented the presence of zoonotic diseases in wild populations of these reptiles. herein we analyzed 48 serum samples from crocodylus acutus (n = 34) and c. moreletii (n = 14) from different sites in the state of quintana roo (mexico) to detect antibodies to leptospira interrogans by means of a microscopic agglutination test (mat). crocodylus acutus and c. moreletii tested positive to ...	2017	27807634
comparison of leptospira interrogans and leptospira biflexa genomes: analysis of potential leptospiral-host interactions.	leptospirosis, a potentially life-threatening disease, remains the most widespread zoonosis caused by pathogenic species of leptospira. the pathogenic spirochaete, leptospira interrogans, is characterized by its ability to permeate human host tissues rapidly and colonize multiple organs in the host. in spite of the efforts taken to comprehend the pathophysiology of the pathogen and the heterogeneity posed by l. interrogans, the current knowledge on the mechanism of pathogenesis is modest. in an ...	2017	28294222
crystallization of fcpa from leptospira, a novel flagellar protein that is essential for pathogenesis.	the protein fcpa is a unique component of the flagellar filament of spirochete bacteria belonging to the genus leptospira. although it plays an essential role in translational motility and pathogenicity, no structures of fcpa homologues are currently available in the pdb. its three-dimensional structure will unveil the novel motility mechanisms that render pathogenic leptospira particularly efficient at invading and disseminating within their hosts, causing leptospirosis in humans and animals. f ...	2017	28291747
animal models of leptospirosis: of mice and hamsters.	pathogenic leptospira sp. are spirochetal bacteria responsible for leptospirosis, an emerging worldwide zoonosis. these spirochetes are very successful pathogens that infect a wide range of hosts such as fish, reptiles, birds, marsupials, and mammals. transmission occurs when chronically infected animals excrete live bacteria in their urine, contaminating the environment. leptospira sp. enter their hosts through damaged skin and mucosa. chronically infected rats and mice are asymptomatic and are ...	2017	28270811
[epidemiological investigation of two leptospirosis death cases in guizhou province].	objective: to conduct an epidemiological investigation of two leptospirosis death cases reported in guizhou province in 2014. methods: the information of the patients were investigated and analyzed. the serological detection, samples of the two patients was detected using elisa and microscopic agglutination test (mat). leptospira carrier status of murine host animal in the living environment of the two patients was investigated in october and november of 2014. leptospires in the kidney were cult ...	2017	28260339
adipose tissue is the first colonization site of leptospira interrogans in subcutaneously infected hamsters.	leptospirosis is one of the most widespread zoonoses in the world, and its most severe form in humans, "weil's disease," may lead to jaundice, hemorrhage, renal failure, pulmonary hemorrhage syndrome, and sometimes,fatal multiple organ failure. although the mechanisms underlying jaundice in leptospirosis have been gradually unraveled, the pathophysiology and distribution of leptospires during the early stage of infection are not well understood. therefore, we investigated the hamster leptospiros ...	2017	28245231
seeking the environmental source of leptospirosis reveals durable bacterial viability in river soils.	leptospirosis is an important re-emerging infectious disease that affects humans worldwide. infection occurs from indirect environment-mediated exposure to pathogenic leptospires through contaminated watered environments. the ability of pathogenic leptospires to persist in the aqueous environment is a key factor in transmission to new hosts. hence, an effort was made to detect pathogenic leptospires in complex environmental samples, to genotype positive samples and to assess leptospiral viabilit ...	2017	28241042
il-10 deficient mice express ifn-γ mrna and clear leptospira interrogans from their kidneys more rapidly than normal c57bl/6 mice.	leptospira interrogans (l. interrogans), the causative agent of leptospirosis, is a widespread zoonotic spirochete that lives a dual lifestyle. l. interrogans infects mice, rats, and wildlife in a persistent and asymptomatic fashion, while also causing productive and acute infections in other mammals such as humans and hamsters. infections in humans can be fatal, accompanied by a cytokine storm and shock-like symptoms. production of il-10 has been noted in both rodent and human infections which ...	2017	28237664
leptospira interrogans serogroup pomona infections in the uk: is there a real threat for farm animals?	current typing of leptospira strains requires a combination of both serological and molecular methods. study of the epidemiology of strains within the pomona serogroup has proved problematic due to the limitations of serological typing methods. this is particularly true of the two main complexes within this group, namely the pomona, monjakov, kennewicki cluster in leptospira interrogans species and the mozdok, tsaratsovo, kunming, altodouro cluster in leptospira kirschneri strains from the south ...	2017	28213528
inhibitory effects of emodin, thymol, and astragalin on leptospira interrogans-induced inflammatory response in the uterine and endometrium epithelial cells of mice.	leptospirosis is a systemic infection that causes, among others, acute kidney injury, acute liver disease, muscle pain, vasculitis, bleeding disorders, and reproductive loss. in an effort to reduce uterine inflammatory responses induced by leptospira, we evaluated the anti-inflammation effects of emodin, thymol, and astragalin in a mouse model. our results showed that treatment with emodin, thymol, and astragalin alleviated uterine inflammation induced by leptospira infection via suppression of ...	2017	28210912
detecting signals of chronic shedding to explain pathogen persistence: leptospira interrogans in california sea lions.	identifying mechanisms driving pathogen persistence is a vital component of wildlife disease ecology and control. asymptomatic, chronically infected individuals are an oft-cited potential reservoir of infection, but demonstrations of the importance of chronic shedding to pathogen persistence at the population-level remain scarce. studying chronic shedding using commonly collected disease data is hampered by numerous challenges, including short-term surveillance that focuses on single epidemics a ...	2017	28207932
distinct antibody responses of patients with mild and severe leptospirosis determined by whole proteome microarray analysis.	leptospirosis is an important zoonotic disease worldwide. humans usually present a mild non-specific febrile illness, but a proportion of them develop more severe outcomes, such as multi-organ failure, lung hemorrhage and death. such complications are thought to depend on several factors, including the host immunity. protective immunity is associated with humoral immune response, but little is known about the immune response mounted during naturally-acquired leptospira infection.	2017	28141801
jarisch-herxheimer reaction among patients with leptospirosis: incidence and risk factors.	a jarisch-herxheimer reaction (jhr) may be precipitated after initiation of chemotherapy in spirochetal diseases, including leptospirosis. however, a clear idea of the importance of jhr in this disease is lacking. the incidence of and risk factors for jhr were investigated retrospectively among 262 patients with confirmed leptospirosis who received amoxicillin treatment in new caledonia and futuna. the overall rate of jhr was 21% (12% in new caledonia and 44% in futuna). two risk factors were in ...	2017	28115662
eyedrop inoculation causes sublethal leptospirosis in mice.	leptospirosis is potentially a fatal zoonosis acquired by contact of skin and mucosal surfaces with soil and water contaminated with infected urine. we analyzed the outcome of infection of c3h/hej mice with leptospira interrogans serovar copenhageni using an enzootic mode of transmission, the conjunctival route. infection led to weight loss and l. interrogans dissemination from blood to urine, and spirochetes were detected in blood and urine simultaneously. the infectious dose that led to consis ...	2017	28115508
immune response and protective profile elicited by a multi-epitope chimeric protein derived from leptospira interrogans.	pathogenic leptospira is the causative agent of leptospirosis, a widely disseminated disease of human and veterinary concern. the development of vaccines that elicit cross-protective immunity through multiple leptospiral serovars has long been pursued. the aim of this study was to develop a novel chimeric multi-epitope fusion antigen, containing sequences of previously studied outer membrane proteins (omps) of leptospira.	2017	28161462
characterization of two new putative adhesins of leptospira interrogans.	we here report the characterization of two novel proteins encoded by the genes lic11122 and lic12287, identified in the genome sequences of leptospira interrogans, annotated, respectively, as a putative sigma factor and a hypothetical protein. the cdss lic11122 and lic12287 have signal peptide spii and spi and are predicted to be located mainly at the cytoplasmic membrane of the bacteria. the genes were cloned and the proteins expressed using escherichia coli. proteinase k digestion showed that ...	2017	28198346
genome-wide transcriptional start site mapping and srna identification in the pathogen leptospira interrogans.	leptospira are emerging zoonotic pathogens transmitted from animals to humans typically through contaminated environmental sources of water and soil. regulatory pathways of pathogenic leptospira spp. underlying the adaptive response to different hosts and environmental conditions remains elusive. in this study, we provide the first global transcriptional start site (tss) map of a leptospira species. rna was obtained from the pathogen leptospira interrogans grown at 30°c (optimal in vitro tempera ...	2017	28154810