Advances in the Research on Leptospira and Leptospirosis

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Public Health Microbiology".

Deadline for manuscript submissions: 15 June 2025 | Viewed by 7643

Special Issue Editors


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Guest Editor
Centro de Bacteriología, Instituto Adolfo Lutz, Sao Paulo 01246-902, SP, Brazil
Interests: leptospirosis; Leptospira

E-Mail Website
Guest Editor
Clinical Hospital, School of Medicine, University of São Paulo, São Paulo, Brazil
Interests: leptospirosis; Leptospira

Special Issue Information

Dear Colleagues,

Leptospirosis is a neglected and re-emerging disease with high morbidity and mortality in humans and animals and is one of the most widespread zoonotic diseases worldwide. Human infections occur through direct contact with the urine of infected animals, such as rodents, livestock, and domesticated pets, and exposure through water or soil. Increasing temperature and extreme weather events, due to global climate change, can prolong the survival of leptospires in the environment, expanding the geographical distribution of these bacteria. Clinical illness in humans can range from a mild, self-limiting acute febrile illness to a severe, life-threatening condition with multiple organ dysfunction. No effective human vaccine is currently available. The pathogenesis of severe leptospirosis is poorly understood, and studies should focus on identifying potential biomarkers for diagnostic and therapeutic targets and prognostic applications. This Special Issue solicits manuscripts on One Health approach, perspectives, challenges, pathology, clinical cases, vaccine development, genomics, and recent advances in the diagnostics of leptospirosis. We welcome both original research articles and comprehensive review papers.

Dr. Eliete Caló Romero
Dr. Antônio José Magaldi
Guest Editors

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Keywords

  • leptospirosis
  • zoonoses
  • environmental exposure
  • epidemiology
  • pathogenesis
  • clinical cases
  • diagnosis
  • genomics
  • serology
  • vaccine
  • One Health

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Published Papers (5 papers)

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Research

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16 pages, 3078 KiB  
Article
The VapBC-4 Characterization Indicates It Is a Bona Fide Toxin-Antitoxin Module of Leptospira interrogans: Initial Evidence for a Role in Bacterial Adaptation
by Bruna Oliveira Pigatto Azevedo, Deborah Kohn Damiano, Aline Florencio Teixeira, Ana Lucia Tabet Oller Nascimento, Luis Guilherme Virgilio Fernandes and Alexandre Paulo Yague Lopes
Microorganisms 2025, 13(4), 879; https://doi.org/10.3390/microorganisms13040879 - 11 Apr 2025
Viewed by 302
Abstract
Toxin-antitoxin (TA) systems are one of the bacterial adaptation mechanisms to adverse conditions. Leptospira interrogans serovar Copenhageni contains nine putative TA systems. To date, only VapBC-3 and VapBC-1 have been experimentally characterized and considered functional modules. This study shows that the VapBC-4 module [...] Read more.
Toxin-antitoxin (TA) systems are one of the bacterial adaptation mechanisms to adverse conditions. Leptospira interrogans serovar Copenhageni contains nine putative TA systems. To date, only VapBC-3 and VapBC-1 have been experimentally characterized and considered functional modules. This study shows that the VapBC-4 module is a novel bona fide TA system constituted by VapB-4 antitoxin and VapC-4 toxin. Overexpression of the recombinant toxin in Escherichia coli resulted in growth inhibition, which was rescued by co-expression of the VapB-4 antitoxin. The toxin-antitoxin binding capability, essential to TA functionality, was demonstrated by dot blot assay in vitro, while the pull-down assay indicates that the toxin and antitoxin interact in vivo. In addition, we confirmed that VapC-4 is a PIN domain endoribonuclease capable of degrading viral MS2 substrate. The transcriptional studies suggest that vapC-4 may be involved in the virulence and adaptability of L. interrogans serovar Copenhageni for adverse environmental conditions. Taken together, these results show that the VapBC-4 module is functional and can be considered a bona fide module. Full article
(This article belongs to the Special Issue Advances in the Research on Leptospira and Leptospirosis)
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14 pages, 2096 KiB  
Article
The Toxin of VapBC-1 Toxin-Antitoxin Module from Leptospira interrogans Is a Ribonuclease That Does Not Arrest Bacterial Growth but Affects Cell Viability
by Deborah K. Damiano, Bruna O. P. Azevedo, George S. C. Fernandes, Aline F. Teixeira, Viviane M. Gonçalves, Ana L. T. O. Nascimento and Alexandre P. Y. Lopes
Microorganisms 2024, 12(8), 1660; https://doi.org/10.3390/microorganisms12081660 - 13 Aug 2024
Cited by 2 | Viewed by 1634
Abstract
Bacterial ubiquitous Toxin-Antitoxin (TA) systems are considered to be important survival mechanisms during stress conditions. In regular environmental conditions, the antitoxin blocks the toxin, whereas during imbalanced conditions, the antitoxin concentration decreases, exposing the bacteria cell to a range of toxic events. The [...] Read more.
Bacterial ubiquitous Toxin-Antitoxin (TA) systems are considered to be important survival mechanisms during stress conditions. In regular environmental conditions, the antitoxin blocks the toxin, whereas during imbalanced conditions, the antitoxin concentration decreases, exposing the bacteria cell to a range of toxic events. The most evident consequence of this disequilibrium is cell growth arrest, which is the reason why TAs are generally described as active in the function of bacterial growth kinetics. Virulence-associated proteins B and C (VapBC) are a family of type II TA system, in which VapC is predicted to display the toxic ribonuclease activity while VapB counteracts this activity. Previously, using in silico data, we designated four VapBC TA modules in Leptospira interrogans serovar Copenhageni, the main etiological agent of human leptospirosis in Brazil. The present study aimed to obtain the proteins and functionally characterize the VapBC-1 module. The expression of the toxin gene vapC in E. coli did not decrease the cell growth rate in broth culture, as was expected to happen within active TA modules. However, interestingly, when the expression of the toxin was compared to that of the complexed toxin and antitoxin, cell viability was strongly affected, with a decrease of three orders of magnitude in colony forming unity (CFU). The assumption of the affinity between the toxin and the antitoxin was confirmed in vivo through the observation of their co-purification from cultivation of E. coli co-expressing vapB-vapC genes. RNAse activity assays showed that VapC-1 cleaves MS2 RNA and ribosomal RNA from L. interrogans. Our results indicate that the VapBC-1 module is a potentially functional TA system acting on targets that involve specific functions. It is very important to emphasize that the common attribution of the functionality of TA modules cannot be defined based merely on their ability to inhibit bacterial growth in a liquid medium. Full article
(This article belongs to the Special Issue Advances in the Research on Leptospira and Leptospirosis)
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11 pages, 4786 KiB  
Communication
Exploring Leptospira interrogans FDAARGOS_203: Insights into AMR and Anti-Phage Defense
by Pavlo Petakh, Valentyn Oksenych and Oleksandr Kamyshnyi
Microorganisms 2024, 12(3), 546; https://doi.org/10.3390/microorganisms12030546 - 8 Mar 2024
Cited by 2 | Viewed by 2428
Abstract
Leptospira, which are known to be important disease-causing agents transmitted between animals and humans, result in significant illness and, in some cases, significant death in human populations. This purpose of this study was to examine the genomic structure of Leptospira interrogans serovar Copenhageni [...] Read more.
Leptospira, which are known to be important disease-causing agents transmitted between animals and humans, result in significant illness and, in some cases, significant death in human populations. This purpose of this study was to examine the genomic structure of Leptospira interrogans serovar Copenhageni strain FDAARGOS_203 to identify the specific genetic factors that contribute to antimicrobial resistance (AMR) and defense against phages. The genome, consisting of two contigs totaling 4,630,574 base pairs, underwent thorough examination for protein-coding sequences, transfer RNA genes, and ribosomal RNA genes. A total of twenty-two antibiotic resistance genes that specifically target essential cellular processes such as cell wall synthesis, DNA replication, and protein synthesis have been identified. Significant among these were gidB, gdpD, and ggsA, each involved in separate aspects of antibiotic resistance. In addition, the investigation explored the defense mechanisms of bacteriophages, revealing the presence of defense islands that contain a range of anti-phage systems, including RM_Type_IV, PrrC, Borvo, CAS_Class1-Subtype-IC, and CAS_Class1-Subtype-IB. This comprehensive genomic analysis enhances our understanding of the molecular mechanisms that determine Leptospira’s ability to adapt to various environments. The identified genetic factors linked to AMR and defense against phages not only enhance our scientific comprehension, but also provide a basis for focused interventions to reduce the impact of leptospirosis. Full article
(This article belongs to the Special Issue Advances in the Research on Leptospira and Leptospirosis)
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11 pages, 1080 KiB  
Brief Report
Diversity of Leptospira Species and Their Rodent Reservoirs in the Guinean Forest
by Siba Pricemou, Barré Soropogui, Fanta Bérété, Michel Bossou Beavogui, Aboubacar Samoura, Mathieu Picardeau, Pascale Bourhy, Noël Tordo and Solène Grayo
Microorganisms 2025, 13(4), 833; https://doi.org/10.3390/microorganisms13040833 - 7 Apr 2025
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Abstract
Leptospirosis is a bacterial zoonosis caused by pathogenic species from the genus Leptospira. Infection mostly occurs through indirect contact with environmental water contaminated with the urine of reservoir animals. Information on the circulation of leptospirosis in West Africa, as well as its [...] Read more.
Leptospirosis is a bacterial zoonosis caused by pathogenic species from the genus Leptospira. Infection mostly occurs through indirect contact with environmental water contaminated with the urine of reservoir animals. Information on the circulation of leptospirosis in West Africa, as well as its potential reservoir hosts, is limited. Therefore, we carried out trapping surveys in the Guinean forest in November 2022, and samples were collected from 42 micromammals. The animals were both morphologically and genetically identified. The lungs and kidneys were screened for Leptospira using Lfb1-gene-targeting real-time PCR, and positive samples were genotyped based on the polymorphic Lfb1 gene. Leptospira species were detected in the kidneys of three micromammals: Mastomys natalensis, Lophuromys sikapusi, and Rattus rattus. Leptospira borgpetersenii was identified in Rattus rattus and Mastomys natalensis that were captured in two different villages. The phylogenetic analysis indicated that this subspecies had previously been detected in one patient in Mayotte, but the reservoir was not identified. A new subspecies of Leptospira kirschneri was isolated in Lophuromys sikapusi from the same village as the Mastomys natalensis positive for L. borgpetersenii. The high diversity of both the reservoirs and Leptospira species in the Guinean forest indicates that we should study other natural regions and reinforce communities’ awareness of Leptospira infection risks in Guinea. Full article
(This article belongs to the Special Issue Advances in the Research on Leptospira and Leptospirosis)
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15 pages, 1340 KiB  
Systematic Review
Diagnostic Advances in Leptospirosis: A Comparative Analysis of Paraclinical Tests with a Focus on PCR
by Elena Ciurariu, Catalin Prodan-Barbulescu, Diana-Maria Mateescu, Paul Tutac, Virgiliu-Bogdan Sorop, Monica Susan and Norberth-Istvan Varga
Microorganisms 2025, 13(3), 667; https://doi.org/10.3390/microorganisms13030667 - 15 Mar 2025
Viewed by 778
Abstract
Leptospirosis is a zoonotic disease with a varied clinical presentation that can mimic other infectious diseases, posing diagnostic challenges. While the Microscopic Agglutination Test (MAT) remains the gold standard for serological diagnosis, its limitations have led to increasing interest in polymerase chain reaction [...] Read more.
Leptospirosis is a zoonotic disease with a varied clinical presentation that can mimic other infectious diseases, posing diagnostic challenges. While the Microscopic Agglutination Test (MAT) remains the gold standard for serological diagnosis, its limitations have led to increasing interest in polymerase chain reaction (PCR) as a rapid and sensitive diagnostic tool. This systematic review evaluates the role and clinical applications of PCR for diagnosing human leptospirosis. We analyzed the sensitivity and specificity of PCR, compared its performance with other diagnostic tests, and assessed the comparative utility of blood and urine samples for PCR testing. Our findings demonstrate that PCR has a high sensitivity and specificity, particularly in the early stages of the disease. Combining PCR with serological tests like MAT can maximize the diagnostic accuracy across different stages of illness. We recommend that PCR be considered a first-line diagnostic test for suspected leptospirosis, especially when rapid diagnosis is crucial. Further research is needed to standardize PCR protocols and explore its potential in differentiating Leptospira species and serotypes. By leveraging the strengths of PCR and combining it with other diagnostic methods, we can significantly improve the diagnosis and management of leptospirosis. Full article
(This article belongs to the Special Issue Advances in the Research on Leptospira and Leptospirosis)
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