Leptospira Bacteria Research Articles

Unveiling Allium sativum Phytocompounds as New Antileptospiral Agents via a Structural‐Based Virtual Screening Approach

AbstractLeptospirosis, a disease of zoonotic origin, is transmitted to humans via the Leptospira bacteria, which infected rats and domestic animals carry. This disease is prevalent in certain regions of South India and North‐East India. As per the Leptospirosis Burden Epidemiology Group (WHO), there are approximately 873,000 reported cases and 48,600 deaths annually. Interestingly, we have identified specific targets that are vital to metabolic processes, lipid synthesis, the flagellar motor protein system, and bacterial chemotaxis. By developing new drugs that target these areas, we could significantly mitigate the risks associated with severe Leptospirosis. This study aims to create a new antileptospiral drug using data from the IMPPAT database. We performed virtual screening with Schrodinger, molecular dynamic simulation, and free energy investigation using GROMACS throughout 50 ns. The primary objective was to identify eight potential therapeutic targets in Leptospira for drug development. The screening process successfully identified promising drug candidates for the treatment of Leptospirosis, specifically IMPHY015116, IMPHY004388, IMPHY004619, IMPHY014919, IMPHY007598, and IMPHY001246. These phytochemical compounds exhibit higher binding energy than conventional drug molecules and show stability in dynamic environments. However, additional studies are required to validate their effect on disease progression and pathogenicity through in vitro studies.

Leptospirosis in the Platypus (Ornithorhynchus anatinus) in Australia: Who Is Infecting Whom?

The platypus (Ornithorhynchus anatinus) is an amphibious, egg-laying mammal of high conservation value that is found only in Australia. The zoonotic bacterium Leptospira interrogans serovar Hardjo was discovered in platypuses in prior studies, but little is known about its epidemiology. Samples in the Platypus Serum Bank were tested in 2023 and the results were combined with historical records. Antibodies against L. interrogans serovar Hardjo were found in 50% of 464 serum samples from 411 platypuses collected from 14 river basins in southeastern Australia between 1981 and 2012; prevalence remained high over three decades in the Shoalhaven River population. Seroprevalence increased with age, suggesting environmental exposure. Individual platypuses had persistent titres, some for six years. Seropositive females lactated, juveniles were recruited into the population, and there were no reports of clinical leptospirosis. Three necropsied platypuses were seropositive and had mild nephritis with leptospires in the renal tubules. The high seroprevalence, persistent titres, lack of disease, mild renal lesions, and renal colonisation suggest the platypus may be a maintenance host. Sympatric cattle had L. interrogans serovar Hardjo titres, but the spatial association with seropositive platypuses was statistically weak. Other mammalian wildlife species and sheep also have L. interrogans serovar Hardjo titres; therefore, a complex ecological network must be considered. A landscape-wide study is recommended to properly assess transmission pathways and confirm who is infecting whom.

Socio-environmental factors associated with small mammal assemblage and Leptospira prevalence in Suburban Areas of Terengganu, Malaysia

Objective: To examine the socio-environmental factors associated with the assemblage of small mammals and the prevalence of Leptospira pathogen in poor suburban communities of Terengganu, Malaysia. Methods: We trapped small mammals from 119 trapping points scattered around three suburban communities of Terengganu using sausage-baited live traps. On the average, we set up five traps for three nights at each sampling point during the trapping period. Kidneys of captured animals were harvested and processed for Leptospira investigation. Additionally, environmental survey was conducted at each trapping point to obtain information about possible variables supporting small mammal assemblage. We used a generalized linear model to evaluate the effect of different socio-environmental variables on small mammals’ assemblage. Results: A total of 89 small mammals, specifically, Rattus norvegicus (n=39), Rattus rattus (n=27), Rattus exulans (n=10), Suncus murinus (n=11), and Tupaia glis (n=2) were captured from 1 385 trap nights. Fourteen individuals (15.7%) of the captured animals tested positive for Leptospira bacteria using PCR detection. Results of our generalized linear model showed only residences bordering vacant lots as the variable positively associated with small mammal occurrence in the three study sites. Conclusions: Small mammal community, especially the often neglected species, could harbour and potentially contribute towards pathogenic Leptospira maintenance in the study sites. To adequately control small mammals’ population and subsequent human zoonoses transmission, it is critical to advocate and promote appropriate infrastructure and suburban services, together with good hygiene practices that can reduce the animals’ access to food and harborage.

Molecular epidemiology of Leptospira spp. serogroup Sejroe associated with chronic bovine leptospirosis

Pathogenic bacteria Leptospira spp. are commonly associated with bovine leptospirosis, characterized chiefly by chronic and subclinical reproductive disorders. Strains from the Sejroe serogroup play a significant role in these chronic genital infections known as Bovine Genital Leptospirosis (BGL), which notably impact cattle health. This study aims to deepen our understanding of BGL by investigating the genetic diversity, geographical distribution, and specific anatomical sites of infection of the causative agents. Initially, uterine fragments and cervicovaginal mucus were collected from 47 cows and subjected to PCR targeting the lipL32 gene. Positive samples in lipL32-PCR (9 samples) underwent genotyping based on the secY gene. Subsequently, sequences were aligned with GenBank entries (108 sequences) and analyzed in silico. All nine sequences from this study were identified as L. interrogans with an identity >99 % to serogroup Sejroe reference strains (Norma and L53). In the broader analysis, the most prevalent species observed was L. borgpetersenii, followed by L. interrogans and L. santarosai. The haplotype network of L. interrogans revealed that haplogroups B and C exclusively included L. interrogans strains of genital origin, while haplogroup A encompassed strains from renal sources as well. These findings underscore the significance of the L. borgpetersenii genotype Hardjobovis and L. interrogans genotype Hardjoprajitno as the predominant circulating strains and highlight the existence of distinct haplogroups of pathogenic leptospires originating from genital sources. We advocate for the use of secY as an effective genetic marker for Leptospira spp. and stress the necessity for additional research prioritizing the genital tract. The outcomes of this study contribute to the development of improved control measures for chronic cattle diseases and provide valuable guidance for future investigations.

Mathematical Analysis and Numerical Simulation on Free-Living Leptospira: A Mathematical Modeling Perspective

A bacterial disease called leptospirosis is very typical in both tropical and subtropical regions. It is a well-known animal-borne illness that is brought on by spiral-shaped bacteria (Leptospira spp.). Both directly and indirectly, the disease can spread to humans through the urine of sick animals or polluted water, soil, or food. Two phases might appear in leptospirosis symptoms. The patient will have symptoms such as fever, chills, headache, muscle aches, vomiting, or diarrhea during the first phase, which is known as the Septicemic phase. In the meantime, the Immune phase, the second, is more severe. Meningitis, liver failure, renal failure, or both could be fatal for the patient. This study aimed to create a mathematical model of leptospirosis disease using free-living bacteria. In the model, interactions occur between people, free-living Leptospira, animal hosts, and animal vectors. The population's characteristics are used to build the model, and the actual issue is used to identify the disease's transmission paths. While the endemic equilibrium is investigated numerically, the disease-free equilibrium is analyzed theoretically. The paper demonstrates that for the established mathematical model with an epidemic threshold $R_0$, analytical and numerical solutions produced the same outcome.

Identification of rodent species confirmed as the cause of leptospirosis disease, along with ecosystem distribution and environmental factors

Background: Leptospirosis outbreaks have been reported in various parts of the world, classifying it as a re-emerging infectious disease. Rats act as the main reservoir for Leptospira spp. bacteria. The Indonesian Ministry of Health reported 1,170 cases of leptospirosis with 106 deaths Case Fatality Rate (CFR 9.1%) in 2020, obtained from 8 provinces. Additionally, in 2021, there was a decrease in cases by 734, but with an increased CFR of 11.4%, with the largest contributors being Central Java and East Java. Objective: To determine the most dominant rodent species confirmed to cause leptospirosis and the distribution of ecosystems and environmental factors that are the dominant causes of leptospirosis. Method: This paper is a narrative literature review study. Articles were searched through online databases such as Google Scholar and PubMed using keywords leptospirosis, rats, ecosystem, and environmental factors, published within the last 5 years. Findings: The identification results showed that Bandicota indica was the most dominant rodent species infected with leptospirosis. This type of rat is a commensal species. Leptospirosis cases occurred in non-forest ecosystems near settlements and coastal areas near settlements. The dominant environmental factors associated with leptospirosis incidence were poor sanitation conditions, indiscriminate waste disposal behavior, and stagnant water. Conclusion: The identification results indicate that Bandicota indica is the most dominant rodent species infected with leptospirosis, being a commensal rat species in non-forest ecosystems near settlements and coastal areas near settlements. The dominant environmental factors associated with leptospirosis incidence include poor sanitation conditions, indiscriminate waste disposal behavior, and stagnant water. Novelty/Originality of this Study: The study's findings confirmed that non-forest and coastal ecosystems near settlements are significant reservoirs for Leptospira bacteria. Additionally, it highlighted the critical role of poor sanitation, indiscriminate waste disposal, and stagnant water as environmental factors contributing to the transmission of leptospirosis.

Responsive refractive index sensor based on actively tuning liquid crystal topological edge states

In this paper, using the electric field regulation and low loss properties of liquid crystal materials, a tunable polarization-separated liquid crystal (LC) topological edge state is proposed, whose potential in responsive sensors (RSs) is explored. Adjustment of the measuring range and sensitivity of the RS can be realized by controlling the orientation angle of LC and the analyte proportion. In the case of a low ratio of analytes, as the LC orientation angle changes from 18° to 0°, the measurement range will also vary from 1–1.8 RIU (refractive index unit) to 1.8–2.3 RIU. When adding the proportion of analytes and the number of periods, the normalized sensitivity will be increased from 0.0759 c/d/RIU (c is the propagation speed of light in vacuum, and d is the normalized thickness) to 0.299 c/d/RIU, leading to a reduction in the detection limit from 2.75 × 10−4 to 5 × 10−6 RIU, so biological indicators such as bacteria Leptospira in rodent urine can be detected.

Surveillance of pathogenic Leptospira among rodents and small mammals in enzootic areas of plague in Pasuruan Indonesia

Leptospirosis is a globally significant yet often overlooked zoonotic infection. Several regions in Indonesia are endemic for leptospirosis, including East Java. Pasuruan a region located in the East Java province of Indonesia, has been recognized as an enzootic area of plague infection. However, the presence of other rodent-borne diseases has not been reported. This study aims to detect the presence of pathogenic Leptospira in rats and small mammals in the enzootic plague area of Pasuruan in Indonesia. This study belongs to the type of observational analytic research with a cross-sectional study design. Simple random sampling was conducted to trap a total of 119 forms 107 rats and 12 small mammal kidneys were analyzed molecularly (PCR) to detect Leptospira bacteria with the LipL32 gene as the target. The study revealed that 7.6% (9/119) of rats in the enzootic areas of plague (Sedaeng, Tosari, Surorowo, Petren, Pakis Bincil, Kutukan) were found to carry Leptospira DNA, indicating a significant difference between infection rates per region (p < 0.0001). Rattus tanezumi was identified as the Leptospirosis reservoir in settlements habitats with a percentage of 13.2%, Rattus tiomanicus was detected at 28.6% in forest habitats, and Rattus exulans was found at 4.4% in both habitats. The findings in our study, it is crucial for the community to increase awareness of the spread of rodent-borne diseases, including Leptospirosis.

Are Pathogenic Leptospira Species Ubiquitous in Urban Recreational Parks in Sydney, Australia?

Leptospirosis is a zoonotic disease caused by the spirochete bacteria Leptospira spp. From December 2017 to December 2023, a total of 34 canine leptospirosis cases were reported in urban Sydney, Australia. During the same spatio-temporal frame, one locally acquired human case was also reported. As it was hypothesised that human residents and companion dogs might both be exposed to pathogenic Leptospira in community green spaces in Sydney, an environmental survey was conducted from December 2023 to January 2024 to detect the presence of pathogenic Leptospira DNA in multipurpose, recreational public parks in the council areas of the Inner West and City of Sydney, Australia. A total of 75 environmental samples were collected from 20 public parks that were easily accessible by human and canine visitors. Quantitative PCR (qPCR) testing targeting pathogenic and intermediate Leptospira spp. was performed, and differences in detection of Leptospira spp. between dog-allowed and dog-prohibited areas were statistically examined. The global Moran's Index was calculated to identify any spatial autocorrelation in the qPCR results. Pathogenic leptospires were detected in all 20 parks, either in water or soil samples (35/75 samples). Cycle threshold (Ct) values were slightly lower for water samples (Ct 28.52-39.10) compared to soil samples (Ct 33.78-39.77). The chi-squared test and Fisher's exact test results were statistically non-significant (p > 0.05 for both water and soil samples), and there was no spatial autocorrelation detected in the qPCR results (p > 0.05 for both sample types). Although further research is now required, our preliminary results indicate the presence of pathogenic Leptospira DNA and its potential ubiquity in recreational parks in Sydney.

Ecological Studies and Epidemiological Aspects of Leptospirosis in the Northeast Region of Brazil

Introduction: Leptospirosis, a globally prevalent zoonotic infection, affects approximately one million people annually. Originating from the bacterium Leptospira, it is transmitted through contact with the urine of reservoir animals, such as rodents. In Brazil, it is endemic, especially in the Northeast region, where poor sanitary conditions contribute to its dissemination. The objective of this study is to analyze the main determining factors for the increase in leptospirosis cases in the Northeast region of Brazil, with an emphasis on rainfall patterns and deficiencies in basic sanitation. Methodology: The methodology consisted of a qualitative exploratory-descriptive bibliographic review of articles published between 2014 and 2024 in Portuguese, English, and Spanish. Inclusion criteria were relevance to the topic, while exclusion criteria involved duplicated articles or those that did not highlight the content of interest. The search was conducted in databases such as LILACS, SciELO, and PubMed, using specific descriptors. The analysis involved careful selection and exhaustive reading for the categorization of results. Results and Discussion: Leptospirosis impacts urban and poor areas, with over one million annual cases globally. Factors such as precipitation and disordered urbanization contribute to its spread, especially in tropical regions. Low-income populations are vulnerable due to the lack of basic sanitation. The unequal distribution reflects socio-economic disparities, with densely populated urban areas being more affected. Conclusion: Leptospirosis poses a challenge to public health, especially in regions with poor sanitary conditions. Effective control requires a comprehensive approach, including improvements in sanitation infrastructure, health education, and rodent control.

Host-pathogen interactions in Leptospirosis

Abstract Leptospirosis is an emerging zoonotic disease, predominant in tropical and sub-tropical climates, with increasing sporadic outbreaks worldwide causing around 60,000 deaths per year. The spirochetal bacteria Leptospira interrogans is the major causative agent of leptospirosis. Canines and livestock animals are particularly susceptible to Leptospira and develop acute symptoms. Rodents, on the other hand, serve as reservoir hosts in which the bacteria chronically colonize the kidneys and get excreted in the urine. Humans are incidental hosts but can develop fulminant disease which can prove fatal. The host immune response to Leptospira spp. remains poorly defined. Leptospiral lipopolysaccharide and lipoproteins can activate TLR4 and TLR2. In addition, leptospires have been shown to activate the NLRP3 inflammasome. However, we observed that L. interrogans induced a poor inflammasome response particularly in mouse macrophages when compared to other bacteria known to activate NLRP3 inflammasome. In contrast, L. interrogans induced robust type I IFN responses in both mouse macrophages and human monocytes. In vivo studies suggest a potential role of type I IFN response in controlling bacteria loads in mouse models. Interestingly, we found the type I IFN response to be dependent on both cGAS-STING and TLR4-TRIF pathways. Further, differences in disease susceptibility in mouse and humans, when infected with Leptospira, may be explained by differences in host-specific immune responses.

The Influencing Factors of The Leptospirosis Prevalence in the Working Area of the Kebonagung Public Health Center

Leptospirosis is an infectious disease in the world caused by the bacterium Leptospira sp. The Kebonagung Public Health Center reported 34 cases of leptospirosis in 2023. The purpose of the study is to determine the factors influencing the leptospirosis prevalence in the Working Area of the Kebonagung Public Health Center. The type of this research was quantitative using a case control study design. The number of samples obtained were 22 cases and 22 controls. The sampling technique used were non probability sampling with purposive sampling. Univariate data analysis construed the frequency distribution, bivariate analysis with Chi-square test, and multivariate analysis with logistic regression test. The results of the bivariate analysis shows that there is an influence between education (p-value=0,018), occupation (p-value=0,037), and past injury (p-value=0,003) on the prevalence of leptospirosis in the working area of the Kebonagung Public Health Center. There is no influence between income (p-value 0,280) and personal hygiene (p-value=0,203) on the leptospirosis prevalence in the working area of the Kebonagung Public Health Cente,. The results of multivariate analysis shows that the factor that most influenced the prevalence of leptospirosis in the working area of the Kebonagung Public Health Center, is past injuries with (p-value=0,006). It is hoped that the public will adopt clean and healthy living habits, especially in caring for wounds and with Increasing leptospirosis surveillance, cross-sectoral coordination, and also familiarization of leptospirosis prevention and control need to be conducted as soon as possible to prevent the prevalence of leptospirosis.

Bacterial community profiles within the water samples of leptospirosis outbreak areas.

Leptospirosis is a water-related zoonotic disease. The disease is primarily transmitted from animals to humans through pathogenic Leptospira bacteria in contaminated water and soil. Rivers have a critical role in Leptospira transmissions, while co-infection potentials with other waterborne bacteria might increase the severity and death risk of the disease. The water samples evaluated in this study were collected from four recreational forest rivers, Sungai Congkak, Sungai Lopo, Hulu Perdik, and Gunung Nuang. The samples were subjected to next-generation sequencing (NGS) for the 16S rRNA and in-depth metagenomic analysis of the bacterial communities. The water samples recorded various bacterial diversity. The samples from the Hulu Perdik and Sungai Lopo downstream sampling sites had a more significant diversity, followed by Sungai Congkak. Conversely, the upstream samples from Gunung Nuang exhibited the lowest bacterial diversity. Proteobacteria, Firmicutes, and Acidobacteria were the dominant phyla detected in downstream areas. Potential pathogenic bacteria belonging to the genera Burkholderiales and Serratia were also identified, raising concerns about co-infection possibilities. Nevertheless, Leptospira pathogenic bacteria were absent from all sites, which is attributable to its limited persistence. The bacteria might also be washed to other locations, contributing to the reduced environmental bacterial load. The present study established the presence of pathogenic bacteria in the river ecosystems assessed. The findings offer valuable insights for designing strategies for preventing pathogenic bacteria environmental contamination and managing leptospirosis co-infections with other human diseases. Furthermore, closely monitoring water sample compositions with diverse approaches, including sentinel programs, wastewater-based epidemiology, and clinical surveillance, enables disease transmission and outbreak early detections. The data also provides valuable information for suitable treatments and long-term strategies for combating infectious diseases.

Seroprevalence of pathogenic Leptospira serogroups in asymptomatic domestic dogs and cats: systematic review and meta-analysis.

Leptospirosis is a neglected zoonotic disease transmitted by contact with the urine of animals infected with pathogenic species of the bacteria Leptospira or by contact with environments contaminated with the bacteria. Domestic dogs and cats may act as reservoirs or as sentinels of environmental contamination with leptospires, posing a public health concern. There is a great diversity of leptospires, and one common way to classify them is into serogroups that provide some information on the host species they are associated with. The aims of this study were: (1) to quantitatively summarize the overall prevalence and serogroup-specific prevalence of antibodies against pathogenic leptospires in asymptomatic dogs and cats and (2) to identify environmental and host characteristics that may affect the prevalence. Three electronic databases and the reference lists of eligible articles were screened, for epidemiological studies conducted between the years 2012-2022. We estimated overall and serogroup-specific prevalence using three-level meta-analysis models and assessed potential sources of heterogeneity by moderator analysis and meta-regression. Eighty-four studies met the inclusion criteria (dog studies 66.7%, cat studies 26.2%, and both species 7.1%). There were significant differences between dogs and cats in the overall prevalence model (P < 0.001), but not in the serogroup-specific model (P>0.05). In dogs, the prevalence of Leptospira interrogans serogroup Canicola was significantly higher than the other pathogenic serogroups (P < 0.001), while in cats there were no significant differences among serogroups (P = 0.373). Moderator analysis showed that the prevalence of L. kirschneri serogroup Grippotyphosa was significantly higher in stray/sheltered dogs than in domiciled dogs (P = 0.028). These results suggest that pathogenic serogroups associated with small mammals are circulating among asymptomatic pets and should be taken into account in the transmission cycle of leptospires, as well as in the standard MAT panel for diagnosis in dogs and cats. It also highlights the importance of including both dogs and cats as potential reservoirs when conducting eco-epidemiological studies in different geographical and ecological areas.

Unraveling the leptospirosis epidemic: tales from the Philippine outbreak – a short communication

Leptospirosis, also known as Weil’s disease, is an emerging zoonotic infection that occurs worldwide but is particularly common in the tropics. There has been an increasing trend of leptospirosis in the Philippines since the outbreak occurred in 2020. The number of reported cases was 182 in 2020, 1661 in 2021, and 2794 in 2022. This present article aimed to access previously published studies on the prevalence, implications, and efforts to combat leptospirosis worldwide, with a particular focus on the Philippines from 2001 to 2023. In writing this article, we conducted a thorough search of databases such as PubMed, Researchgate, Web of Science, Scopus, and Google Scholar within 20 years. This present article found that more than 810 cases were reported from 1 January to 4 March 2023. The Cagayan Valley Region has 103 cases, the Zamboanga Peninsula has 77 cases, and the Western Visayas Region has 176 cases, making them the worst-hit areas. The increase in leptospirosis cases in the Philippines is primarily attributed to several factors. Firstly, the country is prone to natural disasters such as typhoons, floods, and landslides, which increase the risk of water sources and the environment being contaminated with Leptospira bacteria. To address the menace of leptospirosis in the Philippines, we urge the Philippine government to focus on improving healthcare infrastructure, providing swift, reliable, and effective treatments, implementing safety regulations, supplying personal protective equipment to medical authorities, and taking strict actions to improve water sanitation.

SYSTEMATIC REVIEW: ZOONOSIS ASSOCIATED WITH MOUSE AND RAT

Mouse and rat borne zoonotic diseases refer to illnesses that can be transmitted from rodents such as mice and rats to humans. These animals can carry various pathogens, including bacteria, viruses, and parasites, which can cause diseases in humans through direct contact, inhalation of airborne particles, consumption of contaminated food or water, or via vectors such as ticks and fleas. Here are some common mouse and rat zoonotic diseases: Leptospirosis, Hantavirus Pulmonary Syndrome (HPS), Lymphocytic Choriomeningitis (LCM), Rat-Bite Fever (RBF), Salmonellosis dan Pes. Leptospirosis: This bacterial infection is caused by Leptospira bacteria found in the urine of infected rodents. Humans can contract leptospirosis through contact with contaminated water, soil, or food. Symptoms can range from mild flu-like illness to severe complications involving the kidneys, liver, and other organs. Hantavirus Pulmonary Syndrome (HPS): Hantaviruses are transmitted to humans through contact with rodent urine, droppings, or saliva, primarily from deer mice. Inhalation of aerosolized virus particles is the most common route of transmission. HPS can lead to severe respiratory illness, with symptoms including fever, muscle aches, coughing, and potentially fatal pulmonary edema. Lymphocytic Choriomeningitis (LCM): LCM is caused by the Lymphocytic Choriomeningitis Virus (LCMV), which is carried by house mice. Humans can become infected through exposure to rodent urine, droppings, saliva, or nesting materials. LCM can cause flu-like symptoms initially and may progress to more severe neurological complications, including meningitis and encephalitis. Rat-Bite Fever (RBF): This bacterial infection is caused by Streptobacillus moniliformis (commonly associated with rat bites) or Spirillum minus (associated with exposure to rat feces or urine). RBF can result from a bite or scratch from an infected rodent or handling of contaminated materials. Symptoms include fever, rash, joint pain, and in severe cases, endocarditis or meningitis. Salmonellosis: Salmonella bacteria can be carried by rodents, particularly in their feces. Humans can contract salmonellosis through the ingestion of contaminated food or water, as well as through direct contact with rodents or their habitats. Symptoms typically include diarrhea, abdominal cramps, fever, and vomiting. Pes: While commonly associated with fleas that infest rodents like rats, plague bacteria (Yersinia pestis) can also be transmitted directly through contact with infected rodents or their bodily fluids. Plague can manifest as bubonic (swollen lymph nodes), septicemic, or pneumonic forms, with symptoms ranging from fever and chills to respiratory distress and organ failure. Preventing mouse and rat zoonotic diseases involves maintaining good hygiene practices, such as proper food storage, waste disposal, and rodent-proofing buildings. Additionally, avoiding contact with wild rodents and seeking prompt medical attention if exposed to rodents or experiencing symptoms of illness are crucial preventive measures.

Structural investigation of vitamin K epoxide reductase domain-containing protein in Leptospira species: a potential target for the development of new leptospirosis treatments as an alternative to antibiotics

Leptospirosis is a worldwide zoonosis caused by the motile bacterium Leptospira. This disease can cause hemorrhagic symptoms, multi-visceral and renal failures, resulting in one million cases and approximately 60,000 deaths each year. The motility of Leptospira is highly involved in its virulence and is ensured by the presence of two flagella in the periplasm. Several proteins that require the formation of disulfide bridges are essential for flagellar function. In Leptospira, these redox reactions are catalysed by the vitamin K epoxide reductase domain-containing protein (VKORdcp). The aim of the present work was to study the conservation of VKORdcp among Leptospira species and its interactions with putative substrates and inhibitor. Our results evidenced the presence of ten amino acids specific to either pathogenic or saprophytic species. Furthermore, structural studies revealed a higher affinity of the enzyme for vitamin K1 quinone, compared to ubiquinone. Finally, characterisation of the binding of a potential inhibitor revealed the involvement of some VKORdcp amino acids that have not been present in the human enzyme, in particular the polar residue D114. Our study thus paves the way for the future development of Leptospira VKORdcp inhibitors, capable of blocking bacterial motility. Such molecules could therefore offer a promising therapeutic alternative to antibiotics, especially in the event of the emergence of antibiotic-resistant strains. Communicated by Ramaswamy H. Sarma

Inundation Sewers and Mapping the Prevalence Leptospirosis Throughout Rats in Central Java Province

Leptospirosis is a public health threat in countries with tropical climates, like Indonesia. Incidents in Central Java Province are still found every year and still threaten the local community. The goal of this study is to find out what connection there is between sewer puddles and mice that have found leptospira bacteria that can cause leptospirosis in the Regencies of Klaten, Sukoharjo, Karanganyar, and Boyolali in Central Java Province. This research uses descriptive analysis, a cross-sectional design study, and the Geographic Information System (GIS) to carry out mapping. From the research results, it was found that the rat species that were positive for leptospira bacteria were Rattus norvegicus (31%), Rattus tanezumi (44.8%), and Rattus argentiventer (24.1%). Apart from that, only the sampling area and the presence of puddles in the gutter had significant results with the mouse PCR results with p&lt;0.002 and p&lt;0.03. Due to this, there are still many mice infected with leptospira bacteria in Central Java Province. For this reason, it is hoped that the public can increase awareness to always maintain a clean environment so that mice cannot breed freely. Apart from that, related agencies can carry out more monitoring of areas where leptospirosis is still endemic.

Machine learning-based motion tracking reveals an inverse correlation between adhesivity and surface motility of the leptospirosis spirochete

Bacterial motility is often a crucial virulence factor for pathogenic species. A common approach to study bacterial motility is fluorescent labeling, which allows detection of individual bacterial cells in a population or in host tissues. However, the use of fluorescent labeling can be hampered by protein expression stability and/or interference with bacterial physiology. Here, we apply machine learning to microscopic image analysis for label-free motion tracking of the zoonotic bacterium Leptospira interrogans on cultured animal cells. We use various leptospiral strains isolated from a human patient or animals, as well as mutant strains. Strains associated with severe disease, and mutant strains lacking outer membrane proteins (OMPs), tend to display fast mobility and reduced adherence on cultured kidney cells. Our method does not require fluorescent labeling or genetic manipulation, and thus could be applied to study motility of many other bacterial species.

Study of Risk Level Death Based on Clinical Symptoms in Cases of Canine Leptosprirosis in Jakarta, Depok and South Tangerang: Data from January-August 2020

Leptospirosis is a zoonotic disease caused by bacteria Leptospira sp. which causes infection in animals and humans. Dogs infected with leptospirosis showed symptoms such as anorexia, fever, vomiting, weakness, diarrhea and often experience yellowing of the eye area and mucosa around the mouth (icteric) with fatal systemic complications and multi-organ dysfunction, especially in the kidneys and liver. Leptospirosis is an endemic disease in Jakarta. This study aims to identify risk factors that can contribute to canine mortality based on early clinical symptoms that are found when the dog is in an animal health service facility such as a veterinary clinic, veterinary hospital, or independent practice veterinarian. Method was used in this study is clinical manifestations and laboratory examinations and medical records of dogs with suspected leptospirosis. Criteria inclusions were based on aspects of the clinical symptoms of dogs in and around Jakarta. Analysis data used the chi-square with confidence of interval (CI) 95%. Dogs used during the study had ages for puppies (less than 1 year) totaling 13 or 32.50%, for adult dogs over 1 year amounted to 27 or 67.50%, 80% male dogs and 20% female. with 80% maintenance system not housed by the owner. And the conclusion is risk factors for clinical symptoms such as myalgia, symptomatic vomiting of the pulmonary area or shortness of breath and abdominal pain, conjunctival suffusion, anorexia and diarrhea contributed to the high mortality rate leptospirosis during study in dogs 2020.