Transdermal, but not oral mucosa exposure, causes sublethal leptospirosis in mice

ABSTRACT The goal of this study was to determine the timing of Leptospira dissemination after infection using natural physiologic routes and its correlation with signs and symptoms of leptospirosis. Groups of C3H-HeJ mice were sub-lethally infected through exposure of a dermis wound and the oral mucosa to L. interrogans serovar Copenhageni, and compared to mice infected via standard laboratory practice of intraperitoneal inoculation. We found that transdermal infection leads to delayed bacterial dissemination in blood and urine when compared to intraperitoneal infection using the same infectious dose, and that the overlapping presence of L. interrogans in both fluids was twice as long as the standard intraperitoneal infection. Furthermore, dissemination of L. interrogans and disease did not occur in mice infected with the same dose of L. interrogans via the oral mucosa. Over the course of these studies we also observed that the timing of exit of Leptospira from blood and establishment of colonization of the kidney in the second week of infection correlated well with weight loss, but not with hypothermia. Thus, a non-invasive sign of leptospirosis such as weigh loss can be used to monitor bacterial dissemination and disease stage in mice. Our findings underline the importance of precise determination of windows of pathogen dissemination in biological fluids and how the route of infection affects the progression of disease. These studies could help focus the development of better treatment strategies and new technologies for diagnostic use.