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1.
BMJ Case Rep ; 16(1)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604107

RESUMO

We present the case of a young female landscaper who presented to an Australian tertiary hospital with persistent fevers and new pancytopenia. Extensive initial workup for her presenting illness did not identify a cause; however, a detailed history of her occupation revealed she worked heavily with soil on farms that had domestic livestock in addition to rodents. Hence, further serological testing for leptospirosis was performed, revealing a diagnosis of infection with Leptospira interrogans serovar Hardjo. Treatment covering leptospirosis was commenced, and she improved clinically, and her cell counts returned to normal. Pancytopenia is a rare manifestation of leptospirosis and has only been reported in a handful of case studies. We highlight that leptospirosis should be considered as a differential diagnosis in those with fever, and new pancytopaenia, particularly in patients with relevant risk factors for exposure.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Pancitopenia , Feminino , Humanos , Pancitopenia/etiologia , Austrália , Leptospirose/complicações , Leptospirose/diagnóstico , Leptospirose/tratamento farmacológico , Fatores de Risco , Anticorpos Antibacterianos
2.
PLoS Negl Trop Dis ; 16(12): e0010823, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36508469

RESUMO

BACKGROUND: Leptospirosis is an occupational, neglected febrile disease of bacterial origin transmitted between humans and animals. In this manuscript we summarize available data on Leptospira infection in HIV uninfected and in people living with HIV from the Southern African Development Community (SADC) countries, identifying gaps in knowledge and recommend future research priorities. METHODOLOGY: Articles published between 1990 and 2021 were accessed by an online search of Google Scholar and Medline/PubMed performed between February 2020 and July 2022. The STATA program was used for the Meta-analysis. Pooled prevalence values with 95% confidence intervals and heterogeneity were determined. RESULTS: Thirty studies from eight SADC countries, reporting the prevalence on Leptospira were reviewed. A pooled prevalence of 19% (CI: 13-25%), a heterogeneity level of 96% and index score ranging from 2 to 9 was determined. Only four (4) studies reported HIV co-infection status. Three species of Leptospira (Leptospira interrogans (4), L. kirschneri (3), Leptospira borgpetersenii (1) and 23 serogroups were identified. The most frequently reported serogroups were Icterohaemorrhagiae (13), Grippotyphosa and Australis (10) followed by Sejroe (8). CONCLUSION: Studies on human leptospirosis in the SADC region are scarce, especially in people living with HIV. Additional studies aimed at determining the prevalence and the role of the pathogen in people living with HIV, including detailed clinical, molecular and demographic data are recommended.


Assuntos
Infecções por HIV , Leptospira interrogans , Leptospira , Leptospirose , Animais , Humanos , Leptospirose/epidemiologia , Leptospirose/microbiologia , Sorogrupo , Prevalência , Doenças Negligenciadas , Infecções por HIV/complicações , Infecções por HIV/epidemiologia
3.
Int J Mol Sci ; 23(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36555188

RESUMO

Leptospirosis is a neglected infectious disease with global impact on both humans and animals. The increase in urban development without sanitation planning is one of the main reasons for the disease spreading. The symptoms are similar to those of flu-like diseases, such as dengue, yellow fever, and malaria, which can result in a misleading clinical diagnosis. The characterization of host-pathogen interactions is important in the development of new vaccines, treatments, and diagnostics. However, the pathogenesis of leptospirosis is not well understood, and many gaps remain to be addressed. Here, we aimed to determine if Leptospira strains, virulent, culture-attenuated, and saprophytic, and the major outer membrane proteins OmpL37, OmpL1, LipL21, LipL41, and LipL46 are able to adhere to different endothelial, epithelial and fibroblast cell lines in vitro. We showed that virulent leptospires robustly bind to all cells compared to the culture-attenuated and saprophytic lines. The recombinant proteins exhibited certain adhesion, but only OmpL1 and LipL41 were able to bind to several cell lines, either in monolayer or in cell suspension. Blocking OmpL1 with polyclonal antibodies caused a decrease in bacterial binding to cells, contrasting with an increase observed when anti-LipL41 antibodies were used. The adhesion of OmpL1 to HMEC-1 and EA.hy926 was inhibited when cells were pre-incubated with collagen IV, suggesting that both compete for the same cell receptor. We present here for the first time the interaction of five leptospiral outer membrane proteins with several cell lines, and we conclude that LipL41 and OmpL1 may have an impact on leptospiral adhesion to mammalian cells and may mediate the colonization process in leptospiral pathogenesis.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Animais , Humanos , Leptospira interrogans/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Adesinas Bacterianas , Anticorpos Antibacterianos , Mamíferos/metabolismo
4.
Braz J Microbiol ; 53(4): 2233-2240, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36205841

RESUMO

Leptospirosis is an infectious disease caused by Leptospira spp. and affects animals and humans. Reports of leptospirosis in bats have increased and prompted epidemiological research in Brazil. This study aimed to perform a molecular and epidemiological investigation of pathogenic Leptospira spp. in bat kidneys. The total DNA was extracted from 102 kidney samples from chiropterous of different species and cities in Rio Grande do Sul State (RS), Brazil. The polymerase chain reaction was used to amplify a fragment corresponding to lipL32 gene, which is only present in pathogenic Leptospira spp. lipL32 gene was detected in 22.5% (23/102) of the bat kidney tissues. Phylogenetic analysis showed that L. interrogans is circulating in bats in RS. Most species of the bats collected were insectivores. Pathogenic Leptospira spp. detection in bats demonstrated that these animals participate in the infection chain of leptospirosis and, therefore, may play as reservoirs and disseminators of this microorganism. Thus, it is important to monitor infectious agents, especially with zoonotic potential in bats.


Assuntos
Quirópteros , Leptospira interrogans , Leptospira , Leptospirose , Animais , Humanos , Quirópteros/microbiologia , Filogenia , Leptospira interrogans/genética , Brasil/epidemiologia , Leptospira/genética , Leptospirose/epidemiologia , Leptospirose/veterinária , Leptospirose/microbiologia
5.
PLoS Negl Trop Dis ; 16(9): e0010778, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36137081

RESUMO

Leptospirosis, one of the leading global causes of morbidity and mortality, is an emerging public health problem, particularly in large urban centers of developing countries. Leptospirosis results from infection with an organism belonging to the Leptospira genus L. interrogans. The extensive invasive ability has previously been documented, however a mechanism that describes how the organism is internalized by human macrophages and transmigrates through human blood vessel remains poorly understood. In the present study, we utilized a human macrophage and vascular endothelial cell line to study the diverse invasive mechanisms by which L. interrogans infections occur. We found that THP-1 and HUVEC had a diverse expression of cell receptors and L. interrogans entered THP-1 and HUVEC by different pathways. In the macrophage model cell line, ITGB1/FAK-signaling mediated microfilament dependent endocytosis with lysosome fusion, whereas ITGB1/CAV-1/PI3K-signaling mediated microfilament dependent endocytosis and transcytosis without lysosome fusion in the endothelial cell model. Shedding of pathogenic leptospires from HUVEC displayed higher viability than those from THP-1. The monolayer of HUVEC maintained integrity during the infection, while 3D imaging showed that leptospires were transmigrated both intra- and intercellularly. These results indicate that endocytosis of leptospires in human macrophages and human vascular endothelial cells are quite different, macrophages are responsible for eliminating leptospires in the human body during the infection while vascular endothelial cells facilitate dissemination of leptospires from blood vessels into target organs where they cause injury.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Endocitose , Células Endoteliais , Humanos , Macrófagos , Fosfatidilinositol 3-Quinases
6.
Appl Microbiol Biotechnol ; 106(19-20): 6567-6581, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36112204

RESUMO

Leptospirosis is a zoonotic disease caused by pathogenic Leptospira spp., with global implications primarily in tropical countries. However, the mechanisms of leptospiral pathogenesis are still not fully known and not all virulence factors (VFs) have been identified. Budding yeast, Saccharomyces cerevisiae is a popular eukaryotic model which has been used to identify bacterial VFs that target the conserved eukaryotic cellular processes. In this study, we screened for putative VFs of L. interrogans, one of the dominant species causing leptospirosis, by expressing candidate VFs in budding yeast and examining their impact on yeast growth in a high-throughput format. From an initial selection of 288 L. interrogans ORFs, we screened 226 candidate VFs in a yeast growth inhibition assay and identified nine putative VFs in four categories (adhesion, enzymatic, host structure interaction, and immunogenicity). Notably, LIC10280 was highly toxic even when expressed at low copies. We also observed specific subcellular localization for several putative VFs. This study shows that there are still potential L. interrogans VFs that await discovery. KEY POINTS: • High-throughput cloning and expression of leptospiral proteins in yeast. • Heterologous expression of nine leptospiral proteins inhibited yeast growth. • An uncharacterized protein LIC10280 maybe a putative VF for further validation.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Proteínas Fúngicas/metabolismo , Humanos , Leptospira interrogans/genética , Leptospira interrogans/metabolismo , Leptospirose/metabolismo , Leptospirose/microbiologia , Leptospirose/patologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
7.
Front Cell Infect Microbiol ; 12: 917962, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923802

RESUMO

Leptospirosis is an emerging zoonosis caused by pathogenic Leptospira spp. Because rodents are natural hosts of Leptospira, rodent models of pathogenesis have been limited, but are valuable to understand infection in reservoir animals even in the absence of disease. Mouse models of infection provide advantages due to genetic tractability, so developing murine models of Leptospira infection is crucial for further understanding the biology of this organism. Previously our laboratory developed a short-term murine model of Borrelia burgdorferi hematogenous dissemination to investigate the role of adhesion proteins on bacterial survival and dissemination within a host. Here we adapt this model to Leptospira. C3H/HeJ mice are anesthetized, inoculated intravenously, and then bacteria are allowed to circulate for up to twenty-four hours. Mice are euthanized, perfused with saline, and tissues are harvested for culture and DNA purification. Bacterial burdens are determined by quantitative PCR. Reproducible burdens of bacteria were found in tissues upon inoculation with pathogens and non-pathogens, demonstrating the utility of this model to probe different Leptospira species and strains. Pathogenic L. interrogans has a significantly higher burden in blood, liver, kidney, and bladder at one-hour post-inoculation when compared to non-pathogenic L. biflexa. Colonization of the kidney is essential to the life cycle of pathogenic Leptospira in nature. Measurable burdens of non-pathogenic L. biflexa were found in numerous organs and live leptospires were recovered from blood samples for at least three hours post-inoculation, contrary to the previous belief that non-pathogenic leptospires are rapidly cleared. This short-term murine model of Leptospira hematogenous dissemination will allow for the interrogation of virulence factors potentially important for tissue colonization and evasion of host defenses, and represents a novel animal model for investigating determinants of Leptospira infection.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Animais , Modelos Animais de Doenças , Leptospira/genética , Leptospirose/microbiologia , Camundongos , Camundongos Endogâmicos C3H , Zoonoses
8.
Front Cell Infect Microbiol ; 12: 932137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937697

RESUMO

Leptospirosis is a zoonotic infectious disease affecting all vertebrates. It is caused by species of the genus Leptospira, among which are the highly pathogenic L. interrogans. Different mammals can be either resistant or susceptible to the disease which can present a large variety of symptoms. Humans are mostly asymptomatic after infection but can have in some cases symptoms varying from a flu-like syndrome to more severe forms such as Weil's disease, potentially leading to multiorgan failure and death. Similarly, cattle, pigs, and horses can suffer from acute forms of the disease, including morbidity, abortion, and uveitis. On the other hand, mice and rats are resistant to leptospirosis despite chronical colonization of the kidneys, excreting leptospires in urine and contributing to the transmission of the bacteria. To this date, the immune mechanisms that determine the severity of the infection and that confer susceptibility to leptospirosis remain enigmatic. To our interest, differential immune sensing of leptospires through the activation of or escape from pattern recognition receptors (PRRs) by microbe-associated molecular patterns (MAMPs) has recently been described. In this review, we will summarize these findings that suggest that in various hosts, leptospires differentially escape recognition by some Toll-like and NOD-like receptors, including TLR4, TLR5, and NOD1, although TLR2 and NLRP3 responses are conserved independently of the host. Overall, we hypothesize that these innate immune mechanisms could play a role in determining host susceptibility to leptospirosis and suggest a central, yet complex, role for TLR4.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Animais , Bovinos , Cavalos , Humanos , Leptospirose/microbiologia , Mamíferos , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Receptores de Reconhecimento de Padrão , Suínos , Receptor 4 Toll-Like
9.
Front Cell Infect Microbiol ; 12: 917963, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937702

RESUMO

Leptospirosis is an important cause of morbidity and mortality worldwide. Disease severity ranges from asymptomatic colonization to widespread hemorrhage and multiorgan dysfunction. The causative agents, Leptospira spp., are zoonotic Gram-negative spirochetes. One important step in pathogenesis is binding of bacterial adhesins to host components. Previously our laboratory identified two L. interrogans candidate adhesins, LIC11574 and LIC13411, that bind to VE-cadherin in vitro. In the current study, we demonstrate the ability of two strains of pathogenic L. interrogans to disrupt the localization of VE-cadherin, a protein important to maintaining inter-endothelial junctions. Purified MBP-LIC11574 and MBP-LIC13411 bind human dermal microvascular endothelial cells in a pattern reminiscent of VE-cadherin, but do not disrupt VE-cadherin localization. Genes encoding the candidate adhesins from pathogenic Leptospira were cloned in an overexpression vector and introduced into non-pathogenic L. biflexa, creating gain-of-function strains producing LIC11574 or LIC13411. Protein production and localization to the outer membrane were confirmed by Triton X-114 fractionation. Although these strains do not disrupt VE-cadherin localization, production of LIC13411 increases binding of non-pathogenic Leptospira to human endothelial cells and specifically to VE-cadherin. In a short-term murine model of infection, LIC13411 production led to increased burdens of the non-pathogen in the lung, liver, kidney, and bladder. These data confirm the role of LIC13411 as an adhesin in Leptospira spp. and implicate it in dissemination to multiple organs. Importantly, anti-adhesin therapy has been shown to have many benefits over classical antibiotics. Taken together, this work provides novel insight into the pathogenesis of Leptospira spp. and identifies LIC13411 as a potential prophylactic and therapeutic target.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Adesinas Bacterianas/genética , Adesinas Bacterianas/metabolismo , Animais , Células Endoteliais/metabolismo , Humanos , Leptospira/genética , Leptospira interrogans/genética , Leptospira interrogans/metabolismo , Leptospirose/microbiologia , Camundongos
10.
J Vet Med Sci ; 84(10): 1324-1327, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36002297

RESUMO

A 2-year-old male mongoose-scat-detection dog was diagnosed with leptospirosis by urine PCR. The patient developed acute renal failure, hepatic dysfunction, and disseminated intravascular coagulation. Treatment with antibiotics was administered, including ampicillin and doxycycline, and supportive care management was provided. Seroconversion against serogroup Hebdomadis was observed on day 8. The leptospiral gene flaB was detected only in urine collected on day 1, from which Leptospira interrogans ST329 was identified by multilocus sequence typing using seven housekeeping genes. L. interrogans serogroup Hebdomadis ST329 has been isolated from mongooses and humans in Okinawa, Japan. This patient received early treatment with antibiotics, which may have contributed to the early recovery of renal function and removal of L. interrogans from kidney tissue.


Assuntos
Doenças do Cão , Herpestidae , Leptospira interrogans , Leptospira , Leptospirose , Ampicilina , Animais , Antibacterianos/uso terapêutico , Doenças do Cão/diagnóstico , Cães , Doxiciclina , Japão , Leptospira/genética , Leptospira interrogans/genética , Leptospirose/diagnóstico , Leptospirose/veterinária , Masculino , Insuficiência de Múltiplos Órgãos/veterinária , Sorogrupo , Cães Trabalhadores
11.
Front Cell Infect Microbiol ; 12: 936931, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35899053

RESUMO

Leptospira interrogans are pathogenic bacteria responsible for leptospirosis, a zoonosis impacting 1 million people per year worldwide. Leptospires can infect all vertebrates, but not all hosts develop similar symptoms. Human and cattle may suffer from mild to acute illnesses and are therefore considered as sensitive to leptospirosis. In contrast, mice and rats remain asymptomatic upon infection, although they get chronically colonized in their kidneys. Upon infection, leptospires are stealth pathogens that partially escape the recognition by the host innate immune system. Although leptospires are mainly extracellular bacteria, it was suggested that they could also replicate within macrophages. However, contradictory data in the current literature led us to reevaluate these findings. Using a gentamicin-protection assay coupled to high-content (HC) microscopy, we observed that leptospires were internalized in vivo upon peritoneal infection of C57BL/6J mice. Additionally, three different serotypes of pathogenic L. interrogans and the saprophytic L. biflexa actively infected both human (PMA differentiated) THP1 and mouse RAW264.7 macrophage cell lines. Next, we assessed the intracellular fate of leptospires using bioluminescent strains, and we observed a drastic reduction in the leptospiral intracellular load between 3 h and 6 h post-infection, suggesting that leptospires do not replicate within these cells. Surprisingly, the classical macrophage microbicidal mechanisms (phagocytosis, autophagy, TLR-mediated ROS, and RNS production) were not responsible for the observed decrease. Finally, we demonstrated that the reduction in the intracellular load was associated with an increase of the bacteria in the supernatant, suggesting that leptospires exit both human and murine macrophages. Overall, our study reevaluated the intracellular fate of leptospires and favors an active entrance followed by a rapid exit, suggesting that leptospires do not have an intracellular lifestyle in macrophages.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Animais , Bovinos , Humanos , Leptospirose/microbiologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Ratos
12.
PLoS One ; 17(7): e0270568, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35857771

RESUMO

BACKGROUND: The presence of synanthropic rodents, such as Rattus norvegicus, in urban environments generates high costs of prophylaxis and control, in large part due to the environmental transmission of the pathogenic spirochete Leptospira interrogans, which causes leptospirosis. In Salvador, Brazil, The Center for Control of Zoonosis (CCZ) is responsible for planning and implementing Rodent Control Programs (RCP) which are based on chemical rodenticide. However, these strategies have not been standardized for use in developing countries. AIM: This study aimed to identify the effect of a chemical control campaign on the demographic variables of urban R. norvegicus, analyzing relative abundance, sex structure, body mass, and age of the population, as well as the characterization of spatial distribution among households, rodent capture campaigns and interventions. METHODS: This study was carried out during 2015 in three valleys of an urban poor community in Salvador. Individuals of R. norvegicus were systematically captured before (Pre-intervention) and three months (1st post-intervention) and six months (2nd post-intervention) after a chemical control intervention conducted by the CCZ in two valleys of the study area while the third valley was not included in the intervention campaign and was used as a non-intervention reference. We used analysis of variance to determine if intervention affected demographic variables and chi-square to compare proportions of infested households (Rodent infestation index-PII). RESULTS: During the chemical intervention, 939 households were visited. In the pre-intervention campaign, an effort of 310 trap nights resulted in 43 rodents captured, and in the 1st and 2nd, post-intervention campaigns resulted in 47 rodents captured over 312 trap nights and 36 rodents captured over 324 traps-nights, respectively. The rodent infestation index (PII) points did not show a reduction between the period before the intervention and the two periods after the chemical intervention (70%, 72%, and 65%, respectively). Regarding relative abundances, there was no difference between valleys and period before and two periods after chemical intervention (trap success valley 1: 0,18; 0,19; 0,18 / Valley 3 0,15; 0,17; 0,13/ P>0,05). Other demographic results showed that there was no difference in demographic characteristics of the rodent population before and after the intervention, as well as there being no influence of the application of rodenticide on the areas of concentration of capture of rodents between the campaigns. CONCLUSION: Our study indicates that the chemical control was not effective in controlling the population of R. norvegicus and provides evidence of the need for re-evaluation of rodent control practices in urban poor community settings.


Assuntos
Leptospira interrogans , Leptospirose , Doenças dos Roedores , Rodenticidas , Animais , Brasil/epidemiologia , Leptospirose/epidemiologia , Ratos , Doenças dos Roedores/epidemiologia , Roedores
13.
Arch Microbiol ; 204(8): 460, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35792940

RESUMO

Leptospira interrogans serogroup Icterohaemorrhagiae is the predominant pathogen causing leptospirosis in China and is still used as the vaccine strain for the current human inactivated vaccine. Unlike the clade ST17, which is distributed worldwide, ST1 is the most prevalent in serogroup Icterohaemorrhagiae in China. To further characterize leptospiral pathogens, isobaric tags for relative and absolute quantitation and parallel reaction monitoring were used to analyze differences at the proteomic level between serogroup Icterohaemorrhagiae vaccine strain 56001 (ST1) and circulating isolate 200502 (ST17) from different periods. Two hundred and eighty-one proteins were differentially expressed between the circulating isolate and vaccine strain, of which 166 were upregulated (> 1.2-fold change, P < 0.05) and 115 (< 0.8-fold change, P < 0.05) were downregulated. Function prediction revealed that nine upregulated proteins were outer membrane proteins, including several known immunogenic and/or virulence-related proteins, such as ompL1, LipL71, and LipL41. Furthermore, important expression differences in carbohydrate, amino acid, and energy metabolism and transport proteins were identified between both strains from different clusters, suggesting that these differences may reflect metabolic diversity and the potential of the pathogens to adapt to different environments. In summary, our findings provide insights into a better understanding of the component strains of the Chinese human leptospirosis vaccine at the proteomic level. Additionally, these data facilitate evaluating the mechanisms by which pathogenic Leptospira species adapt to the host environment.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , China/epidemiologia , Humanos , Leptospira interrogans/genética , Leptospirose/epidemiologia , Proteômica , Sorogrupo
14.
Front Cell Infect Microbiol ; 12: 926994, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837473

RESUMO

The molecular and cellular pathogenesis of leptospirosis remains poorly understood. Based on comparative bacterial genomics data, we recently identified the hypothetical PF07598 gene family as encoding secreted exotoxins (VM proteins) that mediate cytotoxicity in vitro. To address whether VM proteins mediate in vivo leptospirosis pathogenesis, we tested the hypothesis that VM protein immunization of mice would protect against lethal challenge infection and reduce bacterial load in key target organs. C3H/HeJ mice were immunized with recombinant E. coli-produced, endotoxin-free, leptospiral VM proteins (derived from L. interrogans serovar Lai) in combination with the human-compatible adjuvant, glucopyranoside lipid A/squalene oil-in-water. Mice receiving full length recombinant VM proteins were protected from lethal challenge infection by L. interrogans serovar Canicola and had a 3-4 log10 reduction in bacterial load in the liver and kidney. These experiments show that immunization with recombinant VM proteins prevents leptospirosis clinical pathogenesis and leads to markedly reduced key target organ infection in this animal model. These data support the role of leptospiral VM proteins as virulence factors and suggest the possibility that a VM protein-based, serovar-independent, pan-leptospirosis vaccine may be feasible.


Assuntos
Proteínas de Escherichia coli , Leptospira interrogans , Leptospira , Leptospirose , Animais , Carga Bacteriana , Vacinas Bacterianas/genética , Escherichia coli/genética , Humanos , Rim/patologia , Leptospirose/microbiologia , Fígado/patologia , Camundongos , Camundongos Endogâmicos C3H , Proteínas Recombinantes/genética , Vacinação , Virulência
15.
Vet Med Sci ; 8(5): 1915-1921, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35840123

RESUMO

BACKGROUND: Leptospirosis is an important, neglected zoonotic disease that affects people and animals in humid (sub)tropical regions. Wild canines carry the pathogen and may contaminate natural resources which may then act as a source of human infection. OBJECTIVES: The study was designed to understand the seroprevalence of leptospirosis among domestic and wild canines in Bojnurd County, Northeast Iran. METHODS: A total of 77 serum samples, comprising 29 sera from asymptomatic wild canines [foxes (n = 25) and jackals (n = 4)] and 48 sera from asymptomatic stray dogs, was investigated. Serovars were identified and antibody titres were measured by standard microscopic agglutination test (MAT) using serial serum dilutions. RESULTS: Among all serum samples, 44.1% reacted positively to a Leptospira interrogans serovars. The average percentage of positive reactions was higher in stray dogs than in wild canines although this did not reach statistical significance (55.2% and 37.5%, p = 0.159). Positive reactions with L. i. Pomona, L. i. Australis and L. i. Tarasovi was detected only among jackals and foxes. Among the stray dogs, the highest number of positive sera were for L. i. Grippotyphosa (61.1%) and L. i. Canicola (50%). The highest titre detected was for L. i. canicola (1:1600) in two stray dogs and against L. i. Icterohaemorrhagiae and L. i. Pomona (1:800) in a single jackal. CONCLUSIONS: The study revealed that leptospirosis is endemic among various canine species in the North Khorasan Province of Iran. Detailed monitoring of canines is necessary for better understanding the epidemiology of infection in our and other Iranian regions.


Assuntos
Doenças do Cão , Leptospira interrogans , Leptospira , Leptospirose , Animais , Anticorpos Antibacterianos , Doenças do Cão/epidemiologia , Cães , Raposas , Humanos , Irã (Geográfico)/epidemiologia , Chacais , Leptospirose/epidemiologia , Leptospirose/veterinária , Estudos Soroepidemiológicos , Sorogrupo
16.
Vet Microbiol ; 271: 109489, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35738096

RESUMO

Leptospirosis in ruminants causes reproductive failures leading to important economic losses. This study assessed the occurrence and genetically identified Leptospira spp. in the follicular fluid (FF) of naturally infected live cows. A total of 251 asymptomatic cows from different commercial dairy herds were subjected to ovum-pick up technique for follicular fluid sampling. PCR was performed for Leptospira spp. detection and phylogenetic analysis was later implemented for sequencing. From 251 samples analyzed, 67 (26.7 %) were lipL32-PCR positive, confirming the presence of leptospiral DNA on FF. Furthermore, it was possible to amplify and sequence nine strains after secY nested-PCR. All of them were identified as L. interrogans, with 100 % of identity with strains belonging to Sejroe serogroup. Our findings reveal a high occurrence of infection of Leptospira in the ovarium of asymptomatic cows, highlighting the importance of considering the silent leptospirosis syndrome when screening animals for assisted reproductive biotechniques.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Animais , Bovinos , Feminino , Genitália , Leptospira/genética , Leptospira interrogans/genética , Leptospirose/epidemiologia , Leptospirose/veterinária , Filogenia , Sorogrupo
17.
PLoS Negl Trop Dis ; 16(5): e0010409, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35584087

RESUMO

BACKGROUND: Severe leptospirosis is challenging as it could evolve rapidly and potentially fatal if appropriate management is not performed. An understanding of the progression and pathophysiology of Leptospira infection is important to determine the early changes that could be potentially used to predict the severe occurrence of leptospirosis. This study aimed to understand the kinetics pathogenesis of Leptospira interrogans strain HP358 in the hamster model and identify the early parameters that could be used as biomarkers to predict severe leptospirosis. METHODOLOGY/PRINCIPAL FINDINGS: Male Syrian hamsters were infected with Leptospira interrogans strain HP358 and euthanized after 24 hours, 3, 4, 5, 6 and 7 days post-infection. Blood, lungs, liver and kidneys were collected for leptospiral detection, haematology, serum biochemistry and differential expression of pro- and anti-inflammatory markers. Macroscopic and microscopic organ damages were investigated. Leptospira interrogans strain HP358 was highly pathogenic and killed hamsters within 6-7 days post-infection. Pulmonary haemorrhage and blood vessel congestion in organs were noticed as the earliest pathological changes. The damages in organs and changes in biochemistry value were preceded by changes in haematology and immune gene expression. CONCLUSION/SIGNIFICANCE: This study deciphered haemorrhage as the earliest manifestation of severe leptospirosis and high levels of IL-1ß, CXCL10/IP-10, CCL3/MIP-α, neutrophils and low levels of lymphocytes and platelets serve as a cumulative panel of biomarkers in severe leptospirosis.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Animais , Cricetinae , Modelos Animais de Doenças , Hemorragia , Leptospirose/patologia , Masculino
18.
ACS Infect Dis ; 8(5): 982-997, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35422118

RESUMO

The survival of pathogenic Leptospira in the host depends on its proficiency to circumvent the immune response. These pathogens evade the complement system in serum by enticing and amassing the serum complement regulators onto their surface. ErpY-like lipoprotein, a surface-exposed protein of Leptospira spp., is conserved in the pathogenic Leptospira serovars. The recombinant form of this protein interacts with multiple extracellular matrix (ECM) components and serum proteins such as soluble complement regulators factor H (FH) and factor I (FI). Here, we document that the supplementation of rErpY-like protein (10 µg/mL) in human serum inhibits complement-mediated bacterial cell lysis and augments the viability of Escherichia coli and saprophytic Leptospira biflexa by more than two-fold. Complement regulators FH and FI, when bound to rErpY-like protein, preserve their respective cofactor and protease activity and cleave the complement component C3b. The supplementation of rErpY-like protein (40 µg/mL) in serum ensued in an ∼90% reduction of membrane attack complex (C5b-9/MAC) deposition through the alternative pathway (AP) of complement activation. However, rErpY-like protein could moderately reduce (∼16%) MAC deposition in serum through the classical pathway (CP). In addition, the rErpY-like protein solely initiated the AP, suggesting its role in the rapid consumption and depletion of the complement components. Blocking the pathogenic Leptospira interrogans surface with anti-rErpY-like antibodies resulted in an increase in MAC formation on the bacterial surface, indicating a specific role of the ErpY-like lipoprotein in complement-mediated immune evasion. This study underscores the role of the ErpY-like lipoprotein of Leptospira in complement evasion.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Humanos , Fatores Imunológicos , Leptospira/fisiologia , Leptospira interrogans/metabolismo , Leptospirose/metabolismo , Lipoproteínas/metabolismo
19.
Microbiol Spectr ; 10(3): e0277521, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35446113

RESUMO

Analysis of Leptospira dissemination and colonization of sex organs in rodents is of significant value as it queries the possibility of mammal-to-mammal venereal transmission. The aim of our study was to evaluate the presence and viability of Leptospira interrogans in testes of mice using models of infection that we previously developed. Using sublethal and lethal doses of bioluminescent strains of L. interrogans serovars Manilae and Copenhageni, we visualized the presence of leptospires in testes of C57BL/6 mice as early as 30 min and up to days 3-4 postinfection. This was confirmed by qPCR for the Copenhageni serovar after lethal infection of C3H/HeJ mice. In this model, no histopathological changes were noticed in testis. We further studied persistence of serovar Copenhageni in C3H/HeJ testes after lethal and sublethal infection, with different doses of leptospires. No viable leptospires were recovered from testes of lethally infected mice. However, we found live culturable Leptospira in testes of 19/19 (100%) sublethally infected mice at the acute phase but not at 15 days postinfection, which corresponds to the chronic phase of renal colonization. The data suggest that colonization of testes with live and potentially infectious leptospires is transient and limited to the spirochetemic phase of infection. Further studies are necessary to evaluate if presence of Leptospira in testes of mice leads to excretion in semen and to venereal transmission to female mice. IMPORTANCE Analysis of venereal transmission of Leptospira is important to determine if direct animal to animal transmission occurs, which could impact measures to prevent and treat leptospirosis. The goal of this study was to determine if live Leptospira colonize mouse testes. We found that colonization of mouse testes with live Leptospira was transient and limited to the acute spirochetemic phase of infection and that transient colonization of the testes was insufficient to cause histopathological changes.


Assuntos
Leptospira interrogans , Leptospira , Leptospirose , Animais , Feminino , Leptospira interrogans/genética , Leptospirose/veterinária , Masculino , Mamíferos , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Testículo/patologia
20.
Univ. salud ; 24(1): 55-64, ene.-abr. 2022. tab, graf, ilus
Artigo em Espanhol | LILACS-Express | LILACS, COLNAL | ID: biblio-1361186

RESUMO

Introducción: La leptospirosis es una zoonosis emergente, endémica en Colombia, que afecta tanto animales domésticos como silvestres. Es considerada de riesgo laboral, ya que la transmisión al ser humano está asociada a la exposición con animales o ambientes infectados. En el departamento de Nariño, la producción de cuyes para el consumo humano se realiza en sistemas de crianza tradicionales que podrían favorecer la infección por Leptospira interrogans en esta especie. Objetivo: Detectar molecularmente la infección natural por especies patógenas del género Leptospira en cuyes que son destinados para el consumo humano en el municipio de Pasto. Materiales y métodos: Se tomaron 270 muestras de tejido renal en cuyes sacrificados en dos mataderos. Las muestras fueron analizadas mediante Reacción en Cadena de la Polimerasa (PCR) convencional y coloración diferencial de Warthin Starry (W-S). Resultados: En la evaluación de las 270 muestras, 4 (1,5%) fueron positivas para PCR y una de las muestras demostró la presencia de Leptospira bajo tinción W-S. Conclusiones: Mediante el uso de técnicas moleculares se evidenció L. interrogans en el tejido renal de Cavia porcellus. La circulación del patógeno en esta población representa un riesgo de infección para humanos y animales domésticos en contacto con estos sistemas productivos.


Introduction: Leptospirosis is an emerging zoonosis that is endemic in Colombia and affects both domestic and wild animals. It is considered an occupational risk since human transmission is associated with exposure to infected animals or environments. In the department of Nariño, the production of guinea pigs for human consumption applies traditional rearing systems that could cause animals to get infected with Leptosipira interrogans. Objective: To molecularly identify natural infection by pathogenic species of the genus Leptospira in guinea pigs used for human consumption in the municipality of Pasto (Colombia). Materials and methods: 270 kidney tissue samples were taken from guinea pigs slaughtered in two facilities. Samples were analyzed through conventional polymerase chain reaction (PCR) and Warthin Starry (W-S) differential staining. Results: While 4 (1.5%) out of the 270 samples were categorized as positive using PCR, only 1 sample showed the presence of Leptospira through W-S staining. Conclusions: Molecular techniques were useful to identify L. interrogans in kidney tissue of Cavia porcellus. Dissemination of this pathogen within this population represents an infection risk for humans and domestic animals that are in close proximity to these productive systems.


Assuntos
Humanos , Animais , Cobaias , Zoonoses , Cobaias , Leptospira interrogans , Leptospirose , Doenças dos Animais
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