Abstract
The zoonotic disease leptospirosis is caused by pathogenic species of the genus Leptospira. With the advancement of studies in leptospirosis, several new species are being reported. It has always been a query, whether Leptospira species, serovars, and strains isolated from different geographical locations contribute to the difference in the disease presentations and severity. In an epidemiological surveillance study performed in Malaysia, we isolated seven novel intermediate and saprophytic species (Leptospira semungkisensis, Leptospira fletcheri, Leptospira langatensis, Leptospira selangorensis, Leptospira jelokensis, Leptospira perdikensis, Leptospira congkakensis) from environments and three pathogenic species from rodents (Leptospira borgpetersenii strain HP364, Leptospira weilii strain SC295, Leptospira interrogans strain HP358) trapped in human leptospirosis outbreak premises. To evaluate the pathogenic potential of these isolates, we performed an in vivo and in silico virulence analysis. Environmental isolates and strain HP364 did not induce any clinical manifestations in hamsters. Strain SC295 caused inactivity and weight loss with histopathological changes in kidneys, however, all hamsters survived until the end of the experiment. Strain HP358 showed a high virulent phenotype as all infected hamsters died or were moribund within 7 days postinfection. Lungs, liver, and kidneys showed pathological changes with hemorrhage as the main presentation. In silico analysis elucidated the genome size of strain HP358 to be larger than strains HP364 and SC295 and containing virulence genes reported in Leptospira species and a high number of specific putative virulence factors. In conclusion, L. interrogans strain HP358 was highly pathogenic with fatal outcome. The constituent of Leptospira genomes may determine the level of disease severity and that needs further investigations.
Highlights
Leptospirosis is a zoonotic disease, with rodents being the main transmitting source
All hamsters infected with Leptospira isolates from environments survived, increased in body weight (Figure 1), and showed no clinical presentations until the animals were euthanized on day 14 (Table 2)
L. interrogans strain HP358 induced a fatal outcome in infected hamsters
Summary
Leptospirosis is a zoonotic disease, with rodents being the main transmitting source. There are unique genetic determinants that influence the pathogenic Leptospira to adhere, invade, disseminate, escape from host defense, and establish systemic infection. These genetic elements may be absent or less expressed in intermediate and nonpathogenic Leptospira. Endostatin-like outer membrane proteins, such as LipL32/53, Lsa21/32/63, LenA, LigA, and LigB (Choy et al, 2007; Stevenson et al, 2007; Atzingen et al, 2008; Hauk et al, 2008; Oliveira et al, 2010; Vieira et al, 2010; Domingos et al, 2015), have been identified to participate in the adherence of pathogenic Leptospira to host cells by binding to fibronectin, laminin, and collagens of extracellular matrix, whereas collagenase (Kassegne et al, 2014), invA (Fraser and Brown, 2017), M16 type of metalloprotease/metallopeptidase (Ren et al, 2003), mammalian cell entry protein, and endoflagellum of pathogenic Leptospira have been reported to contribute to leptospiral invasiveness (Liao et al, 2009; Zhang et al, 2012). It is believed that there could be more virulent determinants that are yet to be discovered
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