Dissemination of Leptospira into the intestinal tract resulting in fecal excretion in a hamster model of subcutaneous infection with Leptospirainterrogans.

Leptospirosis, caused by pathogenic Leptospira, is one of the most common zoonotic diseases in the world. It is transmitted to humans through the skin and mucous membranes by contact with water or soil contaminated with urine excreted from infected animals. In human infections, gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea have been frequently observed, but there have been no reports analyzing gastrointestinal lesions in leptospirosis, and the pathological mechanism of gastrointestinal symptoms in leptospirosis remains unclear. In this study, we investigated the pathological changes and the distribution of leptospires in the intestinal wall, and the presence of leptospires in the intestinal contents and feces, of hamsters subcutaneously infected with Leptospira interrogans. Results showed that infected hamsters had macroscopic redness in the jejunum and ileum. Submucosal hemorrhage was observed histologically, and there was no infiltration of inflammatory cells such as neutrophils. There were no obvious changes in the colon, either macroscopically or histologically, and the feces were normal (solid stools). Leptospira was isolated from all the intestinal walls from the small intestine to the colon, the intestinal contents, and the feces. These findings suggest that the invasion of leptospires into the intestinal wall and the associated submucosal hemorrhage may be the cause of the gastrointestinal symptoms observed in leptospirosis. Furthermore, not only the urine of infected animals but also the feces could be a source of infection.

Correlation between renal distribution of leptospires during the acute phase and chronic renal dysfunction in a hamster model of infection with Leptospira interrogans.

BACKGROUND: Leptospirosis has been described as a biphasic disease consisting of hematogenous dissemination to major organs in the acute phase and asymptomatic renal colonization in the chronic phase. Several observational studies have suggested an association between leptospirosis and chronic kidney disease (CKD). We investigated the dynamics of leptospires and histopathological changes in the kidney to understand the relationship between them, and also investigated the extent of renal dysfunction in the acute and chronic phases of leptospirosis using a hamster model. FINDINGS: Hamsters (n = 68) were subcutaneously infected with 1 × 104 cells of the Leptospira interrogans serovar Manilae strain UP-MMC-SM. A total of 53 infected hamsters developed fatal acute leptospirosis, and the remaining 15 hamsters recovered from the acute phase, 13 of which showed Leptospira colonization in the kidneys in the chronic phase. Five asymptomatic hamsters also had renal colonization in the chronic phase. Immunofluorescence staining showed that leptospires were locally distributed in the renal interstitium in the early acute phase and then spread continuously into the surrounding interstitium. The kidneys of the surviving hamsters in the chronic phase showed patchy lesions of atrophic tubules, a finding of chronic tubulointerstitial nephritis, which were substantially consistent with the distribution of leptospires in the renal interstitium. The degree of atrophic tubules in kidney sections correlated statistically with the serum creatinine level in the chronic phase (rs = 0.78, p = 0.01). CONCLUSION: Subcutaneous infection with pathogenic leptospires could cause acute death or chronic leptospirosis in hamsters after surviving the acute phase. We suggest that the renal distribution of leptospires during the acute phase probably affected the extent of tubular atrophy, leading to CKD.

Acquisition of genetic mutations in Group A Streptococci at infection site and subsequent systemic dissemination of the mutants with lethal mutations in a streptococcal toxic shock syndrome mouse model.

Streptococcal toxic shock syndrome (STSS) is caused mainly by Streptococcus pyogenes (Group A Streptococci, GAS), and it has a fatality rate of 25%. Mutations in CsrRS and RopB, which suppress the transcription of many virulence factors, were recently found in clinical isolates from STSS patients, but it is not fully understood when and where GAS acquires the mutations in the host. To resolve this question, we used our mouse model of human STSS to recover GAS strains from injections sites, spleens and blood of moribund mice with STSS-like symptoms, and analyzed the sequence of the covR/covS genes and ropB gene that encode CsrRS and RopB. Fifteen out of twenty mice that were inoculated transdermally into muscles with GAS organisms became moribund with STSS-like symptoms after more than 20 days after inoculation. We found that all the disseminated GAS strains recovered from the blood and spleens of the moribund mice had mutations in either the covR genes or the covS genes. The mutation sites in the GAS strains recovered from the blood and spleen were identical in each mouse, whereas the strains recovered from the muscles included a mix of disseminated strains, other mutant strains, and the parent strain. The mutant strains killed mice significantly earlier than the parent strain. Our data indicated that GAS organisms remained at the injection site, and various mutants appeared there, among which the strain that acquires the mutation in the covR/S gene is expected to overexpress various virulence factors simultaneously and cause systemic infection such as STSS.