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Clinical Microbiology Reviews Apr 2001Leptospirosis is a worldwide zoonotic infection with a much greater incidence in tropical regions and has now been identified as one of the emerging infectious diseases.... (Review)
Review
Leptospirosis is a worldwide zoonotic infection with a much greater incidence in tropical regions and has now been identified as one of the emerging infectious diseases. The epidemiology of leptospirosis has been modified by changes in animal husbandry, climate, and human behavior. Resurgent interest in leptospirosis has resulted from large outbreaks that have received significant publicity. The development of simpler, rapid assays for diagnosis has been based largely on the recognition that early initiation of antibiotic therapy is important in acute disease but also on the need for assays which can be used more widely. In this review, the complex taxonomy of leptospires, previously based on serology and recently modified by a genotypic classification, is discussed, and the clinical and epidemiological value of molecular diagnosis and typing is also evaluated.
Topics: Animals; Dogs; Guinea Pigs; Humans; Leptospira; Leptospirosis; Rats
PubMed: 11292640
DOI: 10.1128/CMR.14.2.296-326.2001 -
PLoS Neglected Tropical Diseases May 2019The causative agents of leptospirosis are responsible for an emerging zoonotic disease worldwide. One of the major routes of transmission for leptospirosis is the...
The causative agents of leptospirosis are responsible for an emerging zoonotic disease worldwide. One of the major routes of transmission for leptospirosis is the natural environment contaminated with the urine of a wide range of reservoir animals. Soils and surface waters also host a high diversity of non-pathogenic Leptospira and species for which the virulence status is not clearly established. The genus Leptospira is currently divided into 35 species classified into three phylogenetic clusters, which supposedly correlate with the virulence of the bacteria. In this study, a total of 90 Leptospira strains isolated from different environments worldwide including Japan, Malaysia, New Caledonia, Algeria, mainland France, and the island of Mayotte in the Indian Ocean were sequenced. A comparison of average nucleotide identity (ANI) values of genomes of the 90 isolates and representative genomes of known species revealed 30 new Leptospira species. These data also supported the existence of two clades and 4 subclades. To avoid classification that strongly implies assumption on the virulence status of the lineages, we called them P1, P2, S1, S2. One of these subclades has not yet been described and is composed of Leptospira idonii and 4 novel species that are phylogenetically related to the saprophytes. We then investigated genome diversity and evolutionary relationships among members of the genus Leptospira by studying the pangenome and core gene sets. Our data enable the identification of genome features, genes and domains that are important for each subclade, thereby laying the foundation for refining the classification of this complex bacterial genus. We also shed light on atypical genomic features of a group of species that includes the species often associated with human infection, suggesting a specific and ongoing evolution of this group of species that will require more attention. In conclusion, we have uncovered a massive species diversity and revealed a novel subclade in environmental samples collected worldwide and we have redefined the classification of species in the genus. The implication of several new potentially infectious Leptospira species for human and animal health remains to be determined but our data also provide new insights into the emergence of virulence in the pathogenic species.
Topics: Animals; Asia; Evolution, Molecular; Genome, Bacterial; Genomics; Humans; Leptospira; Leptospirosis; Phylogeny; Virulence; Zoonoses
PubMed: 31120895
DOI: 10.1371/journal.pntd.0007270 -
Microbes and Infection Dec 2019
Topics: Adaptation, Physiological; Artifacts; Cell Culture Techniques; Host-Pathogen Interactions; Leptospira; Leptospirosis; Models, Biological
PubMed: 31226394
DOI: 10.1016/j.micinf.2019.06.001 -
Current Topics in Microbiology and... 2015The outer membrane (OM) is the front line of leptospiral interactions with their environment and the mammalian host. Unlike most invasive spirochetes, pathogenic... (Review)
Review
The outer membrane (OM) is the front line of leptospiral interactions with their environment and the mammalian host. Unlike most invasive spirochetes, pathogenic leptospires must be able to survive in both free-living and host-adapted states. As organisms move from one set of environmental conditions to another, the OM must cope with a series of conflicting challenges. For example, the OM must be porous enough to allow nutrient uptake, yet robust enough to defend the cell against noxious substances. In the host, the OM presents a surface decorated with adhesins and receptors for attaching to, and acquiring, desirable host molecules such as the complement regulator, Factor H.Factor H. On the other hand, the OM must enable leptospires to evade detection by the host's immune system on their way from sites of invasion through the bloodstream to the protected niche of the proximal tubule. The picture that is emerging of the leptospiral OM is that, while it shares many of the characteristics of the OMs of spirochetes and Gram-negative bacteria, it is also unique and different in ways that make it of general interest to microbiologists. For example, unlike most other pathogenic spirochetes, the leptospiral OM is rich in lipopolysaccharide (LPS). Leptospiral LPS is similar to that of Gram-negative bacteria but has a number of unique structural features that may explain why it is not recognized by the LPS-specific Toll-like receptor 4 of humans. As in other spirochetes, lipoproteins are major components of the leptospiral OM, though their roles are poorly understood. The functions of transmembrane outer membrane proteins (OMPs) in many cases are better understood, thanks to homologies with their Gram-negative counterparts and the emergence of improved genetic techniques. This chapter will review recent discoveries involving the leptospiral OM and its role in leptospiral physiology and pathogenesis.
Topics: Bacterial Outer Membrane Proteins; Cell Membrane; Immunity, Innate; Leptospira; Lipopolysaccharides
PubMed: 25388136
DOI: 10.1007/978-3-662-45059-8_8 -
Current Opinion in Infectious Diseases Oct 2016The definitive diagnosis of leptospirosis, which results from infection with spirochetes of the genus Leptospira, currently relies on the use of culture, serological... (Review)
Review
PURPOSE OF REVIEW
The definitive diagnosis of leptospirosis, which results from infection with spirochetes of the genus Leptospira, currently relies on the use of culture, serological testing (microscopic agglutination testing), and molecular detection. The purpose of this review is to describe new molecular diagnostics for Leptospira and discuss advancements in the use of available methods.
RECENT FINDINGS
Efforts have been focused on improving the clinical sensitivity of Leptospira detection using molecular methods. In this review, we describe a reoptimized pathogenic species-specific real-time PCR (targeting lipL32) that has demonstrated improved sensitivity, findings by two groups that real-time reverse-transcription PCR assays targeting the 16S rrs gene can improve detection, and two new loop-mediated amplification techniques. Quantitation of leptospiremia, detection in different specimen types, and the complementary roles played by molecular detection and microscopic agglutination testing will be discussed. Finally, a protocol for Leptospira strain subtyping using variable number tandem repeat targets and high-resolution melting will be described.
SUMMARY
Molecular diagnostics have an established role for the diagnosis of leptospirosis and provide an actionable diagnosis in the acute setting. The use of real-time reverse-transcription PCR for testing serum/plasma and cerebrospinal fluid, when available, may improve the detection of Leptospira without decreasing clinical specificity.
Topics: Humans; Leptospira; Leptospirosis; Molecular Diagnostic Techniques; Molecular Typing; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 27537829
DOI: 10.1097/QCO.0000000000000295 -
FEBS Letters Aug 2020Leptospires are highly invasive spirochetes equipped with efficient strategies for dissemination in the host. The Leptospira genus currently comprises 64 species divided... (Review)
Review
Leptospires are highly invasive spirochetes equipped with efficient strategies for dissemination in the host. The Leptospira genus currently comprises 64 species divided into two major clades: the saprophytes composed of nonpathogenic, free-living organisms, and the pathogens encompassing all the species that cause mild or severe infections in humans and animals. While saprophytes are highly susceptible to the lytic action of the complement system, pathogenic (virulent) strains have evolved virulence strategies that allow efficient colonization of a variety of hosts and target organs, including mechanisms to circumvent hosts' innate and acquired immune responses. Pathogenic Leptospira avoid complement-mediated killing by recruiting host complement regulatory proteins and by targeting complement proteins using own and host-expressed proteases. This review outlines the role of complement in eradicating saprophytic Leptospira and the stratagems adopted by pathogenic Leptospira to maneuver the host complement system for their benefit.
Topics: Animals; Complement System Proteins; Humans; Immune Evasion; Leptospira; Leptospirosis
PubMed: 32153015
DOI: 10.1002/1873-3468.13768 -
Parasitology Apr 2018Leptospirosis is a zoonotic bacterial disease of global importance. A large spectrum of asymptomatic animal hosts can carry the infection and contribute to the burden of... (Review)
Review
Leptospirosis is a zoonotic bacterial disease of global importance. A large spectrum of asymptomatic animal hosts can carry the infection and contribute to the burden of human disease. Environmental sources of human contamination also point to the importance of a hydrotelluric reservoir. Leptospirosis can be caused by as many as 15 different pathogenic or intermediate Leptospira species. However, classification of these bacteria remains complicated through the use of both serological and genetic classification systems that show poor correlation. With the advent of molecular techniques, DNA-based barcoding offers a conceptual framework that can be used for leptospirosis surveillance as well as source tracking. In this review, we summarize some of the current techniques, highlight significant successes and weaknesses and point to the future opportunities and challenges to successfully establish a widely applicable barcoding scheme for Leptospira.
Topics: Animals; DNA Barcoding, Taxonomic; Disease Reservoirs; Environmental Microbiology; Genotyping Techniques; Humans; Leptospira; Leptospirosis; Phylogeny; Zoonoses
PubMed: 28716157
DOI: 10.1017/S0031182017001147 -
Acta Tropica Feb 2018Leptospirosis is a zoonotic disease caused by a diverse pathogenic leptospira species and serovars. The disease is transmitted directly following contact with infected... (Review)
Review
INTRODUCTION
Leptospirosis is a zoonotic disease caused by a diverse pathogenic leptospira species and serovars. The disease is transmitted directly following contact with infected urine and other body fluids or indirectly after contact with water or soil contaminated with infected urine.
OBJECTIVES
While a wide range of domestic and wild animals are known to be reservoirs of the disease, occupation, international travel and recreation are beginning to assume a center stage in the transmission of the disease. The objective of this study is to review available literatures to determine the extent to which these aforementioned risk factors aid the transmission, increase incidence and outbreak of leptospirosis in Malaysia.
STUDY DESIGN
The review was conducted based on prevalence, incidence, and outbreak cases of leptospirosis among human and susceptible animals predisposed to several of the risk factors identified in Malaysia.
METHODS
Literature searchers and reviews were conducted based on articles published in citation index journals, Malaysian ministry of health reports, periodicals as well as reliable newspapers articles and online media platforms. In each case, the newspapers and online media reports were supported by press briefings by officials of the ministry of health and other agencies responsible.
RESULTS
The disease is endemic in Malaysia, and this was attributed to the large number of reservoir animals, suitable humid and moist environment for proliferation as well as abundant forest resources. Over 30 different serovars have been detected in Malaysia in different domestic and wild animal species. This, in addition to the frequency of flooding which has increased in recent years, and has helped increase the risk of human exposure. Occupation, recreation, flooding and rodent population were all identified as an important source and cause of the disease within the study population.
CONCLUSION
There is an urgent need for the government and other stakeholders to intensify efforts to control the spread of the disease, especially as it greatly affect human health and the tourism industry which is an important component of the Malaysian economy. The risk of infection can be minimized by creating awareness on the source and mode of transmission of the disease, including the use of protective clothing and avoiding swimming in contaminated waters. Moreover, improved diagnostics can also help reduce the suffering and mortalities that follow infection after exposure to infection source.
Topics: Animals; Humans; Leptospira; Leptospirosis; Malaysia; Zoonoses
PubMed: 29217379
DOI: 10.1016/j.actatropica.2017.12.010 -
PLoS Neglected Tropical Diseases Nov 2021Leptospirosis is a re-emerging zoonosis with a global distribution. Surface-exposed outer membrane proteins (SE-OMPs) are crucial for bacterial-host interactions....
Leptospirosis is a re-emerging zoonosis with a global distribution. Surface-exposed outer membrane proteins (SE-OMPs) are crucial for bacterial-host interactions. SE-OMPs locate and expose their epitope on cell surface where is easily accessed by host molecules. This study aimed to screen for surface-exposed proteins and their abundance profile of pathogenic Leptospira interrogans serovar Pomona. Two complementary approaches, surface biotinylation and surface proteolytic shaving, followed by liquid chromatography tandem-mass spectrometry (LC-MS/MS) were employed to identify SE-OMPs of intact leptospires. For quantitative comparison, in-depth label-free analysis of SE-OMPs obtained from each method was performed using MaxQuant. The total number of proteins identified was 1,001 and 238 for surface biotinylation and proteinase K shaving, respectively. Among these, 39 were previously known SE-OMPs and 68 were predicted to be localized on the leptospiral surface. Based on MaxQuant analysis for relative quantification, six known SE-OMPs including EF- Tu, LipL21, LipL41, LipL46, Loa22, and OmpL36, and one predicted SE-OMPs, LipL71 were found in the 20 most abundant proteins, in which LipL41 was the highest abundant SE-OMP. Moreover, uncharacterized LIC14011 protein (LIP3228 ortholog in serovar Pomona) was identified as a novel predicted surface βb-OMP. High-abundance leptospiral SE-OMPs identified in this study may play roles in virulence and infection and are potential targets for development of vaccine or diagnostic tests for leptospirosis.
Topics: Bacterial Outer Membrane Proteins; Chromatography, High Pressure Liquid; Humans; Leptospira interrogans serovar pomona; Leptospirosis; Proteomics; Tandem Mass Spectrometry
PubMed: 34843470
DOI: 10.1371/journal.pntd.0009983 -
Frontiers in Cellular and Infection... 2022Leptospirosis is a zoonotic infectious disease affecting all vertebrates. It is caused by species of the genus , among which are the highly pathogenic . Different... (Review)
Review
Leptospirosis is a zoonotic infectious disease affecting all vertebrates. It is caused by species of the genus , among which are the highly pathogenic . 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.
Topics: Animals; Cattle; Horses; Humans; Leptospira; Leptospira interrogans; Leptospirosis; Mammals; Mice; Mice, Inbred C57BL; Rats; Receptors, Pattern Recognition; Swine; Toll-Like Receptor 4
PubMed: 35937697
DOI: 10.3389/fcimb.2022.932137