Translocation of Mycobacterium tuberculosis after experimental ingestion

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.

Culturomics Discloses Anti-Tubercular Enterococci Exclusive of Pulmonary Tuberculosis: A Preliminary Report

“…Such a heterogeneous natural history of tuberculosis in neonates in the Lübeck series of cases may partly be explained by different gut microbiota maturation in the neonates [ 37 ]. Indeed, translocating M. canettii and M. tuberculosis has been shown to lead to both disseminating in the lymphatic and lung tissues after experimental gavage in mice [ 18 , 38 ]. It would be interesting to further document E. mundtii and E. casseliflavus interactions with M. tuberculosis in a mouse model, to observe interference with M. tuberculosis gut survival, translocation, and recirculation in the lungs.…”

“…In order to further explore the prevalence of two bacteria of interest ( E. casseliflavus and E. mundtii ) in the stools of TB-positive and TB-negative patients, 150 stools specimens were tested with molecular PCR-based assays as previously described [ 18 ]. For each sample, DNA were extracted from 200 mg of stool with a semi-automated method using an EZ1 DNA Tissue Kit (Qiagen, Hilden, Germany) and EZ1 Advanced XL extractor (Qiagen).…”

“…Fresh culture colonies were suspended in DPBS, adjusted to 15 McFarland and serial dilution was performed in DPBS. The anti-tuberculosis activity of these seven bacteria was then tested against eight MTBC clinical strains including M. tuberculosis lineage 1 strain (CSURP9458) , M. tuberculosis lineage 2 strain Beijing CSUR Q1316 [ 18 ] M. tuberculosis lineage 3 strain CSURP7204, M. tuberculosis lineage 4 strain CSUR P7739 [ 22 ], M. africanum strain CSURP7201, M. canettii strain CIPT140010059, and M. bovis strain CSURP7222 [ 23 ]. All strains were cultured in Middlebrook 7H10 culture medium and calibrated to 10 7 CFU/mL, as previously described [ 24 ].…”

TranslocatingMycobacterium ulcerans: an experimental model

“…Interestingly, it is possible to determine mycolactones in Buruli ulcer lesions, but not in patients’ blood [16]. It should be noted that translocation property is shared with mycobacteria of the Mycobacterium tuberculosis complex, in which experimental translocation has been shown for Mycobacterium canettii [17] and M. tuberculosis [18], there are no experimental data or clinical observations to our knowledge for mycobacteria of the Mycobacterium leprae complex.…”

“…After translocation, the fate of M. ulcerans differs considerably from that of mycobacteria of the M. tuberculosis complex. The latter spread into the lung and other highly vascularized organs [18], while M. ulcerans did not spread into any organs in the rat model.…”