Research Article: Adipose tissue is the first colonization site of Leptospira interrogans in subcutaneously infected hamsters

Date Published: February 28, 2017

Publisher: Public Library of Science

Author(s): Ryo Ozuru, Mitsumasa Saito, Takaaki Kanemaru, Satoshi Miyahara, Sharon Y. A. M. Villanueva, Gerald L. Murray, Ben Adler, Jun Fujii, Shin-ichi Yoshida, R. Mark Wooten.


Leptospirosis is one of the most widespread zoonoses in the world, and its most severe form in humans, “Weil’s disease,” may lead to jaundice, hemorrhage, renal failure, pulmonary hemorrhage syndrome, and sometimes,fatal multiple organ failure. Although the mechanisms underlying jaundice in leptospirosis have been gradually unraveled, the pathophysiology and distribution of leptospires during the early stage of infection are not well understood. Therefore, we investigated the hamster leptospirosis model, which is the accepted animal model of human Weil’s disease, by using an in vivo imaging system to observe the whole bodies of animals infected with Leptospira interrogans and to identify the colonization and growth sites of the leptospires during the early phase of infection. Hamsters, infected subcutaneously with 104 bioluminescent leptospires, were analyzed by in vivo imaging, organ culture, and microscopy. The results showed that the luminescence from the leptospires spread through each hamster’s body sequentially. The luminescence was first detected at the injection site only, and finally spread to the central abdomen, in the liver area. Additionally, the luminescence observed in the adipose tissue was the earliest detectable compared with the other organs, indicating that the leptospires colonized the adipose tissue at the early stage of leptospirosis. Adipose tissue cultures of the leptospires became positive earlier than the blood cultures. Microscopic analysis revealed that the leptospires colonized the inner walls of the blood vessels in the adipose tissue. In conclusion, this is the first study to report that adipose tissue is an important colonization site for leptospires, as demonstrated by microscopy and culture analyses of adipose tissue in the hamster model of Weil’s disease.

Partial Text

Leptospirosis, which is mainly caused by the pathogenic spirochete Leptospira interrogans, is one of the most widespread and potentially fatal zoonoses in the world [1]. Many wild and domestic animals can serve as reservoir hosts for leptospires and the brown rat (Rattus norvegicus) is the most important source of human infections [2]. Rat urine containing leptospires contaminates environmental soil and water, and leptospires infect humans and livestock when they are exposed to a contaminated environment [3]. The early stage of leptospirosis is similar to that of other febrile illnesses, but the most severe clinical manifestations of leptospirosis are jaundice, renal failure and hemorrhage (Weil’s disease) and sometimes pulmonary hemorrhage syndrome [4–6]. Because L. interrogans has more than 250 serovars [2], effective universal vaccination is not yet available.

We performed this study to determine where in the body leptospires colonize and grow at the early phase of an infection. Although the clinical manifestations of leptospirosis are relatively mild, they may eventually worsen and become lethal if appropriate therapy is not initiated. It is already known that when pathogenic leptospires infect percutaneously, they immediately move into the bloodstream and persist there during the leptospiremic phase of the illness [2, 25]. Our study is the first report suggesting that leptospires initially colonize the blood vessels of adipose tissues in the hamster model of Weil’s disease, as based on the results of IVIS, microscopy, and culture.