- Haemolysin Sph2 of Leptospira interrogans induces cell apoptosis via intracellular reactive oxygen species elevation and mitochondrial membrane injury. [Journal Article]
- CMCell Microbiol 2019; 21(1):e12959
- Leptospira interrogans causes widespread leptospirosis in humans and animals, with major symptoms of jaundice and haemorrhage. Sph2, a member of the sphingomyelinase haemolysins, is an important viru…
Leptospira interrogans causes widespread leptospirosis in humans and animals, with major symptoms of jaundice and haemorrhage. Sph2, a member of the sphingomyelinase haemolysins, is an important virulence factor for leptospire. In this study, the function and mechanism of Sph2 in the pathogenesis of leptospirosis were investigated to further understand the pathogenesis of leptospire. Real-time PCR analysis of expression levels during cell invasion showed that sph2 gene expression was transiently induced in human umbilical vein endothelial cells (HUVECs), human embryo liver cells (L02), and human epithelial lung cells (L132), with expression levels reaching a peak after 45 min of infection. Further functional analysis of recombinant Sph2 (rSph2) by LDH assays and confocal microscopy showed that rSph2 can be internalised by cells both by causing cell membrane damage and by a damage-independent clathrin-mediated endocytosis pathway. Subsequently, rSph2 is able to translocate to mitochondria, which led to an increase in the levels of reactive oxygen species (ROS) and a decrease of the mitochondrial membrane potential (ΔΨm). Further flowcytometry analyses after rSph2 exposure showed that 28.7%, 31%, and 27.3% of the HUVEC, L02, and L132 cells, respectively, became apoptotic. Because apoptosis could be decreased with the ROS inhibitor N-acetyl cysteine, these experiments suggested that rSph2 triggers apoptosis through mitochondrial membrane damage and ROS elevation. The ability of leptospiral haemolysin rSph2 to cause apoptosis likely contributes to the pathogenesis of leptospirosis.
- High frequency of genital carriers of Leptospira sp. in sheep slaughtered in the semi-arid region of northeastern Brazil. [Journal Article]
- TATrop Anim Health Prod 2019; 51(1):43-47
- Although some studies in sheep have indicated leptospire colonization of the genital tract, further studies are needed to clarify the role of genital carriers in this species. Thus, this study aimed …
Although some studies in sheep have indicated leptospire colonization of the genital tract, further studies are needed to clarify the role of genital carriers in this species. Thus, this study aimed to evaluate the colonization of pathogenic leptospires in the genital and urinary tract of slaughtered sheep. Fifty-seven adult, female woolless sheep destined for slaughter were used. Renal (n = 57), bladder (n = 57), ovary (n = 34), uterine tube (n = 44), and uterus (n = 33) samples were collected for molecular detection of Leptospira sp. DNA, and blood samples (n = 57) for serological testing. The molecular testing was performed using polymerase chain reaction (PCR), and the serological testing was performed using microscopic serum agglutination test (MAT). Samples with amplifying DNA were subjected to genetic sequencing. In total, leptospiral DNA was found in the tissues of 44 (77.2%) sheep, whereas only nine animals were positive on both PCR and MAT; there was slight agreement between PCR and MAT techniques (k = 0.0268; p = 0.684). In 61 (54.9%) genital tract and in five (4.4%) urinary tract samples, the leptospiral DNA was detected, with significant difference (p < 0.001). The genes of one sample from the uterine tube and another from the bladder were sequenced and demonstrated 99% similarity to Leptospira interrogans. Anti-Leptospira antibodies were detected in 11 (19.3%) of the tested animals. The results reinforce the importance of the genital tract as an extra-renal site of colonization, suggesting the possibility of venereal transmission in sheep.
- Experimental Infection of Rattus norvegicus by the Group II Intermediate Pathogen, Leptospira licerasiae. [Journal Article]
- AJAm J Trop Med Hyg 2018; 99(2):275-280
- Leptospira licerasiae serovar Varillal, a group II intermediate pathogen species/serovar discovered in the Peruvian Amazon city of Iquitos, is commonly recognized in this region by sera from humans (…
Leptospira licerasiae serovar Varillal, a group II intermediate pathogen species/serovar discovered in the Peruvian Amazon city of Iquitos, is commonly recognized in this region by sera from humans (at least 40% seroprevalence) without a known clinical history of leptospirosis. This high frequency of human seroreactivity remains unexplained. To test the hypothesis that the oral route of infection might explain the high rate of human seroreactivity against L. licerasiae, an experimental infection model using Rattus norvegicus was developed, given that rats were one of the original reservoir hosts identified as being colonized by this leptospire. Sprague-Dawley rats were experimentally exposed via mucosa, direct gastric gavage, or parenteral inoculation with nine different isolates of L. licerasiae originally isolated from Peruvian humans, peridomiciliary rodents, and wildlife. As shown by quantitative polymerase chain reaction of kidney tissue, Leptospira infection via these routes of infection was equally successful. Importantly, the data show that L. licerasiae infects R. norvegicus via the oral route, leading to renal colonization. Not only do these findings confirm the infectiousness of group II Leptospira, but also they underscore the potential importance of oral as well as mucosal and transcutaneous routes of Leptospira infection.
- A model for leptospire dynamics and control in the Norway rat (Rattus norvegicus) the reservoir host in urban slum environments. [Journal Article]
- EEpidemics 2018; 25:26-34
- Leptospirosis is a zoonosis that humans can contract via contact with animal reservoirs directly or with water contaminated with their urine. The primary reservoir of pathogenic leptospires within ur…
Leptospirosis is a zoonosis that humans can contract via contact with animal reservoirs directly or with water contaminated with their urine. The primary reservoir of pathogenic leptospires within urban slum environments is the Norway rat (Rattus norvegicus). Motivated by the annual outbreaks of human leptospirosis in slum urban settings, the within population infection dynamics of the Norway rat were investigated in Pau da Lima, an community in Salvador, Brazil. A mechanistic model of the dynamics of leptospire infection was informed by extensive field and laboratory data was developed and explored analytically. To identify the intraspecific transmission route of most importance, a global sensitivity analysis of the basic reproduction number to its components was performed. In addition, different methods of rodent control were investigated by calculating target reproduction numbers. Our results suggest environmental transmission plays an important role in the maintenance of infection in the rodent population. To control numbers of wild Norway rats, combinations of controls are recommended but environmental control should also be investigated to reduce prevalence of infection in rats.
- Modelling leptospirosis in livestock. [Journal Article]
- TPTheor Popul Biol 2018; 121:26-32
- New Zealand has one of the highest (per capita) incidences of human leptospirosis in the world. It is the highest occurring occupational disease in New Zealand, often transmitted from livestock such …
New Zealand has one of the highest (per capita) incidences of human leptospirosis in the world. It is the highest occurring occupational disease in New Zealand, often transmitted from livestock such as deer, sheep and cattle to humans. A cyclical model, showing the dynamics of infection of leptospirosis in farmed livestock in New Zealand, is presented. The limit cycle, bifurcation diagram and quasi-R0 value of the system are determined. Leptospire death rate is used as a control parameter. Previously published parameter values are used in a case study to produce figures demonstrating analytical results. The model is used to predict conditions under which the infection will persist in the population.
- [Detection of Leptospire spp. in animals and in environmental samples from peridomestic areas in NicaraguaDetecção de Leptospira spp. em animais e em amostras ambientais de áreas peridomiciliares na Nicarágua]. [Journal Article]
- RPRev Panam Salud Publica 2018; 42:e26
- CONCLUSIONS: This research demonstrates that pets and environment conditions play an important role in the emergence of outbreaks of leptospirosis, and confirms the endemic behavior of the disease in Nicaragua.
- Overview of laboratory methods to diagnose Leptospirosis and to identify and to type leptospires. [Review]
- IMInt Microbiol 2017; 20(4):184-193
- Leptospirosis is a virulent zoonosis with a global distribution. Pathogenic spirochetes of the genus Leptospira are responsible for this disease, and the primary animal reservoirs are rodentvvvs. Dir…
Leptospirosis is a virulent zoonosis with a global distribution. Pathogenic spirochetes of the genus Leptospira are responsible for this disease, and the primary animal reservoirs are rodentvvvs. Direct and indirect contact with infected urine constitutes the main route of transmission. Renal failure and advanced abortions are frequently observed in animals affected by leptospirosis, causing serious problems for farms. In humans, there is a high rate of mortality (10 percent), and farmers and persons in contact with water are frequently exposed. However, vaccines and strict prevention measures confer protection against leptospirosis. Serological tests facilitate the detection and identification of leptospire strains. Such tests are based on specific surface antigen recognition and are used for clinical analyses. To determine which serovars circulate in the environment, leptospires must be typed. Molecular methods, such as restriction enzyme-based techniques and the sequencing of specific regions, permit serovar identification. Unfortunately, although there are numerous techniques, they are not very efficient, and thus, new methods must be developed. With the advent of genomic sequencing, a substantial amount of information regarding leptospire genomes is now available, facilitating the selection of regions to discriminate between strains. Typing is important for both epidemiologic purposes and clinical analyses.
- Bid-Induced Release of AIF/EndoG from Mitochondria Causes Apoptosis of Macrophages during Infection with Leptospira interrogans. [Journal Article]
- FCFront Cell Infect Microbiol 2017; 7:471
- Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species. Leptospire-induced macrophage apoptosis through the Fas/FasL-caspase-8/3 pathway plays an important role…
Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species. Leptospire-induced macrophage apoptosis through the Fas/FasL-caspase-8/3 pathway plays an important role in the survival and proliferation of the pathogen in hosts. Although, the release of mitochondrial apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in leptospire-infected macrophages has been described, the mechanisms linking caspase and mitochondrion-related host-cell apoptosis has not been determined. Here, we demonstrated that leptospire-infection induced apoptosis through mitochondrial damages in macrophages. Apoptosis was caused by the mitochondrial release and nuclear translocation of AIF and/or EndoG, leading to nuclear DNA fragmentation. However, the mitochondrion-related CytC-caspase-9/3 pathway was not activated. Next, we found that the release and translocation of AIF and/or EndoG was preceded by the activation of the BH3-interacting domain death agonist (Bid). Furthermore, our data demonstrated that caspase-8 was activated during the infection and caused the activation of Bid. Meanwhile, high reactive oxygen species (ROS) trigged by the infection caused the dephosphorylation of Akt, which also activated Bid. In conclusion, Bid-mediated mitochondrial release of AIF and/or EndoG followed by nuclear translocation is a major mechanism of leptospire- induced apoptosis in macrophages, and this process is modulated by both caspase-8 and ROS-Akt signal pathways.
- Evidence of multiple intraspecific transmission routes for Leptospira acquisition in Norway rats (Rattus norvegicus). [Journal Article]
- EIEpidemiol Infect 2017; 145(16):3438-3448
- Infectious diseases frequently have multiple potential routes of intraspecific transmission of pathogens within wildlife and other populations. For pathogens causing zoonotic diseases, knowing whethe…
Infectious diseases frequently have multiple potential routes of intraspecific transmission of pathogens within wildlife and other populations. For pathogens causing zoonotic diseases, knowing whether these transmission routes occur in the wild and their relative importance, is critical for understanding maintenance, improving control measures and ultimately preventing human disease. The Norway rat (Rattus norvegicus) is the primary reservoir of leptospirosis in the urban slums of Salvador, Brazil. There is biological evidence for potentially three different transmission routes of leptospire infection occurring in the rodent population. Using newly obtained prevalence data from rodents trapped at an urban slum field site, we present changes in cumulative risk of infection in relation to age-dependent transmission routes to infer which intra-specific transmission routes occur in the wild. We found that a significant proportion of animals leave the nest with infection and that the risk of infection increases throughout the lifetime of Norway rats. We did not observe a significant effect of sexual maturity on the risk of infection. In conclusion, our results suggest that vertical and environmental transmission of leptospirosis both occur in wild populations of Norway rats.
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- Risk factors of Leptospira infection in Mediterranean periurban micromammals. [Journal Article]
- ZPZoonoses Public Health 2018; 65(1):e79-e85
- Urbanization of natural areas can change abiotic factors, providing artificial sources of humidity in summer and decreasing variation of temperatures in winter. Our study aimed at document risk facto…
Urbanization of natural areas can change abiotic factors, providing artificial sources of humidity in summer and decreasing variation of temperatures in winter. Our study aimed at document risk factors of infection in mammal reservoirs of pathogenic Leptospira in the human/wildlife interface of a large metropolitan area. We hypothesize that survival of Leptospira and thus their prevalence in animal reservoirs should be higher in residential areas than in natural habitats, especially after the hot, dry Mediterranean summers. We established the prevalence of Leptospira spp. and identified the serovars in 353 urine samples from micromammals (chiefly the wood mouse Apodemus sylvaticus, n = 266) using direct immunofluorescence and PCR. Animals were captured in spring and autumn, 2011-2012, in two natural parks and two adjacent residential areas in periurban Barcelona (NE Spain). Overall observed prevalence of infection was 11%, ranking between 8% and 13% in the better represented host species. We observed marked differences between seasons; the probability of finding a micromammal infected in spring was three times greater than in autumn (almost four times for wood mouse). Prevalence was not related with type of habitat, micromammal relative abundance or sex of the animal. Three Leptospira species were confirmed: Leptospira interrogans (47% of cases), Leptospira borgpetersenii (41%) and Leptospira kirschneri (12%). The serovars most commonly detected were those typically hosted by rodents, and serovars Ballum and Icterohemorrhagiae were the only ones found in autumn. People living in periurban Barcelona and those visiting the natural areas of the metropolitan area face hazard of infection with rodent-borne Leptospira, especially during spring.