Leptospira spp., a genus in the stage of diversity and genomic data expansion

Highlights

• Leptospira genus diversity has been significantly increased over the past few years

• Extensive genomic data will improve actual molecular typing methods for the whole genus, not restricted to pathogenic species

• Genetic variability must be studied in the clinical/environmental context

Abstract

Leptospirosis is a widespread global zoonotic bacterial disease with a noteworthy human-animal-ecosystem interface. The disease presents different clinical manifestations and a high mortality and morbidity rates in humans and animals throughout the world. Characterization and correct classification of Leptospira isolates is essential for a better understanding the epidemiological properties of the disease. In the last ten years, molecular typing tools have been developed and applied to this field. These methods together with the availability of hundreds of new whole genome sequences that belong to known and new described species are shaping the understanding and structure of the entire genus.

Introduction

Leptospirosis is a widespread global zoonotic bacterial disease with a noteworthy human-animal-ecosystem interface (Petrakovsky et al., 2014). The disease is caused by pathogenic spirochetes of the genus Leptospira that has recently been redefined as composed by 66 different species that include more than 300 serovars (Guglielmini et al., 2019; Thibeaux et al., 2018a, Thibeaux et al., 2018b; Vincent et al., 2019). Leptospirosis occurred in all continents except Antarctica and its incidence is increasing predominantly in impoverished populations inhabiting developing countries with tropical climates (Adler and de la Peña Moctezuma, 2010) Recently, the global leptospirosis burden was estimated to cause more than 1 million severe cases and approximately 60,000 deaths per year, suggesting that the burden of leptospirosis is comparable or even higher than some other important neglected tropical diseases, including visceral leishmaniasis, severe dengue, echinococcosis, and cysticercosis (Costa et al., 2015; Picardeau, 2015). However, the disease burden is even today underestimated, due to the low warning in medical services, poor quality of surveillance data, the difficulty of diagnosis, and the poor sensitivity of the standard diagnostic tests (Cerqueira and Picardeau, 2009).

The disease can be acquired through direct contact with infected animals or indirectly through contact with urine-contaminated environments, where the main route of transmission is water. All mammals can be carriers of pathogenic leptospires, including pinnipeds and bats, but the presence of leptospires has also been described in other classes such as birds, amphibians, reptiles and possibly fish (Dietrich et al., 2015; Ellis, 2015; Jobbins and Alexander, 2015; Mgode et al., 2015). Asymptomatic reservoir animals, mainly rodents, maintained pathogenic leptospires in their renal tubules excreting the bacteria through the urine, contaminating the environment, where they can survive for months. For this reason, the three main tracks presenting transmission risk were summarized as water-based, rodent-borne and livestock/pet-borne infection (Levett, 2015). Climatic conditions strongly influence the transmission of leptospires, which require warm, humid conditions for survival. The bacteria persist for weeks to months following their excretion into water or moist soil (Haake and Levett, 2015).

Humans are considered a dead-end host and are highly susceptible to infection with many serovars (Mwachui et al., 2015). The disease may range from a very mild and self-limited illness to severe multisystem illness that includes high fever, renal failure, jaundice, and aseptic meningitis as well as a plethora of other signs and symptoms. Weil's syndrome, a severe leptospirosis manifestation, is characterized by renal failure, jaundice, and splenomegaly. However, since 1980s, the incidence of severe pulmonary hemorrhage leptospirosis (SPHL) has increased, carrying in many settings a mortality rate over 50%, and does not always coincide with the classic manifestations of severe leptospirosis. The reasons behind the emergence of SPHL are not yet known, but the emergence of new bacterial strains or the acquisition of virulence traits by strains in the endemic regions are among the main possibilities (Truong and Coburn, 2012).

Vaccines based on killed-whole leptospires from the most prevalent serovars circulating in a determined setting are available, both for animals and humans, but many of them present side effects or a short duration of efficacy and incomplete cross-protection (Picardeau, 2015).

For the above-mentioned reasons, the characterization and correct classification of Leptospira isolates is essential for a better understanding of the epidemiological properties of the disease. In the past ten years many molecular typing tools have been developed and applied to this field, such as Multilocus Sequence Typing (MLST) together with the availability of hundreds of new whole genome sequences that are shaping the understanding and structure of the entire genus.

The purpose of this review was to describe classic (serotyping), and post-genomic typing methods and the advances made in the application of new sequencing technologies. We also discuss themes of genomic structure and evolution of this important human pathogen.