Leptospiral Biofilms and the Impact on Leptospirosis Chronic Kidney Disease

Leptospirosis, caused by the pathogenic spirochete Leptospira spp., is the most widespread zoonosis throughout the world and a re-emerging infectious disease with public health impacts because of its increasing incidence and epidemic proportions. Due to the endemic regional consistency and the similarity of pathophysiological changes in the kidney, evidences suggest a positive association between leptospirosis and chronic kidney diseases, whereby leptospirosis could be a risk factor for chronic kidney diseases. Taiwan has been recognized as an epidemic area with the highest incidence and prevalence rates of chronic kidney diseases. The most important findings from our previous cohort studies is to ensure that asymptomatic exposure to leptospiral infection carry the risk for chronic kidney diseases. We also established the chronic leptospira-infection murine model in C57BL/6 mice characterized by mild tubulo-interstitial lesions in kidneys and findings revealed the colonization of leptospires was examined in the proximal renal tubules of the kidneys at day 28 and 86 post-infection. Previous publications have demonstrated Leptospira spp. are able to form biofilms on abiotic surfaces working as a physical barrier to antibiotic agents. Hence, we hypothesize that colonization of leptospires in the kidneys may form biofilms, induce antibiotic tolerance and modulate the host immune responses. In this study, we will investigate the structure/functional characteristics and significance of biofilm development by leptospires in vitro and in vivo infection models. This study will discuss the impact of leptospiral biofilms in the pathogenesis of leptospirosis chronic kidney diseases and the goal will provide the basis for future anti-biofilm therapeutic strategies aimed at effectively inhibiting/eradicating leptospiral biofilms in infected kidneys.The specific aims for each year to be completed are:Year 1: To identify leptospiral biofilm production in renal tissue-biofilm models from chronically infected mice;Year 2: To evaluate leptospiral biofilm in modulating the immune responses;Year 3: To characterize and elucidate the composition and structure of in vitro biofilms developed by pathogenic and non-pathogenic Leptospira spp.

Project ID:PC10907-1100
External Project ID:MOST109-2314-B182-050-MY3