Translocation of Mycobacterium tuberculosis after experimental ingestion
Mustapha Fellag1,2, Ahmed Loukil2, Jamal Saad1,2
1IHU Méditerranée Infection, Marseille, France.
Abstract:
Human tuberculosis is a life-threatening infection following the inhalation of Mycobacterium tuberculosis, while the closely related bacteria Mycobacterium bovis and Mycobacterium canettii are thought to be transmitted by ingestion. To explore whether M. tuberculosis could also infect individuals by ingestion, male BALBc mice were fed 2 x 106 CFUs of M. tuberculosis Beijing or phosphate-buffered saline as a negative control, over a 28-day experiment. While eight negative control mice remained disease-free, M. tuberculosis was identified in the lymph nodes and lungs of 8/14 mice and in the spleens of 4/14 mice by microscopy, PCR-based detection and culture. Whole-genome sequencing confirmed the identity of the inoculum and the tissue isolates. In these genetically identical mice, the dissemination of M. tuberculosis correlated with the results of the culture detection of four intestinal bacteria. These observations indicate that ingested M. tuberculosis mycobacteria can translocate, notably provoking lymphatic tuberculosis.
Insights
Ingested Mycobacterium tuberculosis can cause infection and lymphatic tuberculosis in mice. This study shows that oral transmission of tuberculosis is possible, challenging previous assumptions about inhalation as the sole route.
Area of Science:
- Microbiology
- Infectious Diseases
- Immunology
Background:
- Human tuberculosis is typically caused by inhalation of Mycobacterium tuberculosis.
- Mycobacterium bovis and Mycobacterium canettii are believed to be transmitted through ingestion.
- The potential for oral transmission of M. tuberculosis in humans remains largely unexplored.
Purpose of the Study:
- To investigate whether Mycobacterium tuberculosis can infect individuals through ingestion.
- To determine if ingested M. tuberculosis can translocate and cause disease.
Main Methods:
- Male BALB/c mice were orally administered M. tuberculosis Beijing (2 x 10^6 CFUs) or a phosphate-buffered saline control.
- Experiments were conducted over a 28-day period.
- Detection of M. tuberculosis in tissues (lymph nodes, lungs, spleen) was performed using microscopy, PCR, and culture. Whole-genome sequencing confirmed isolate identity.
Main Results:
- M. tuberculosis was detected in the lymph nodes and lungs of 8/14 mice and in the spleens of 4/14 mice.
- Eight control mice remained disease-free.
- Dissemination correlated with intestinal bacterial presence, suggesting a role for gut microbiota.
Conclusions:
- Ingested Mycobacterium tuberculosis can translocate from the gastrointestinal tract.
- Oral ingestion of M. tuberculosis can lead to lymphatic tuberculosis in mice.
- This finding suggests a potential alternative route for tuberculosis transmission.
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