Progenitor “<i>Mycobacterium canettii</i>” Clone Responsible for Lymph Node Tuberculosis Epidemic, Djibouti

Blouin, Yann; Cazajous, Géraldine; Dehan, Céline; Soler, C.; Vong, Rithy; Hassan, Mohamed Osman; Hauck, Yolande; Boulais, Christian; Andriamanantena, D.; Martinaud, Christophe; Martin, Elyette; Pourcel, Christine; Vergnaud, Gilles

doi:10.3201/eid2001.130652

Cited by 63 publications

(67 citation statements)

References 24 publications

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“…M. canettii strains are remarkable, rare mycobacteria, which are almost exclusively isolated from patients in the region of the Horn of Africa (35, 36). Their mode of transmission seems to be different to M. tuberculosis because no human-to-human transmission of M. canettii strains was yet reported (18,35,37). M. canettii strains might have a yet-unknown, possibly aquatic, environmental reservoir where different strains can get in frequent direct contact, thereby enhancing the possibilities of HGT (10,17,38,39).…”

Section: Discussionmentioning

confidence: 99%

“…However, we cannot entirely exclude the possibility of a distinct, yet unknown mechanism of DNA transfer operating in M. canettii strains. Nonetheless, it is plausible that such types of genome blending seen in our M. canettii recombinants, in addition to particular reductive evolution events, such as the loss of lipooligosaccharide production through recombination between two pks5 genes (21), or the loss of elements from the cobalamin-vitamin B12 synthesis pathway (10,18,44), have accelerated adaptation of an ancestral generalist Mycobacterium to the challenging conditions imposed by new hosts. Because the different exchanged genome segments can be large enough to contain (multiple) whole operons, HGT can also boost simultaneous creation of new functions.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, this type of HGT was termed distributive conjugal transfer (DCT) (16). Detection of mosaic sequence arrangements in M. canettii genomes (10,11,17,18) raised the issue whether similar molecular mechanisms might be active in tuberculosis-causing mycobacteria and/or in mycobacteria, in general.…”

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confidence: 99%

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Key experimental evidence of chromosomal DNA transfer among selected tuberculosis-causing mycobacteria

Boritsch

Khanna

Pawlik

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

101

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Horizontal gene transfer (HGT) is a major driving force of bacterial diversification and evolution. For tuberculosis-causing mycobacteria, the impact of HGT in the emergence and distribution of dominant lineages remains a matter of debate. Here, by using fluorescenceassisted mating assays and whole genome sequencing, we present unique experimental evidence of chromosomal DNA transfer between tubercle bacilli of the early-branching Mycobacterium canettii clade. We found that the obtained recombinants had received multiple donor-derived DNA fragments in the size range of 100 bp to 118 kbp, fragments large enough to contain whole operons. Although the transfer frequency between M. canettii strains was low and no transfer could be observed among classical Mycobacterium tuberculosis complex (MTBC) strains, our study provides the proof of concept for genetic exchange in tubercle bacilli. This outstanding, now experimentally validated phenomenon presumably played a key role in the early evolution of the MTBC toward pathogenicity. Moreover, our findings also provide important information for the risk evaluation of potential transfer of drug resistance and fitness mutations among clinically relevant mycobacterial strains.recombination | DNA transfer | tuberculosis | Mycobacterium canettii | evolution

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Key experimental evidence of chromosomal DNA transfer among selected tuberculosis-causing mycobacteria

Boritsch

Khanna

Pawlik

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

101

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“…Only approximately 60 isolates of STB have been described so far, most of which from the Horn of Africa. Increasing epidemiological evidence suggests STBs are environmental organisms that only occasionally infect humans [67]. …”

Section: The Nature Of Mtbc Genomic Diversitymentioning

confidence: 99%

Consequences of genomic diversity in Mycobacterium tuberculosis

Coscollá

Gagneux

2014

Seminars in Immunology

390

370

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The causative agent of human tuberculosis, Mycobacterium tuberculosis complex (MTBC), comprises seven phylogenetically distinct lineages associated with different geographical regions. Here we review the latest findings on the nature and amount of genomic diversity within and between MTBC lineages. We then review recent evidence for the effect of this genomic diversity on mycobacterial phenotypes measured experimentally and in clinical settings. We conclude that overall, the most geographically widespread Lineage 2 (includes Beijing) and Lineage 4 (also known as Euro-American) are more virulent than other lineages that are more geographically restricted. This increased virulence is associated with delayed or reduced pro-inflammatory host immune responses, greater severity of disease, and enhanced transmission. Future work should focus on the interaction between MTBC and human genetic diversity, as well as on the environmental factors that modulate these interactions.

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“…Published cases indicate that in Djibouti, cervical lymphadenitis is significantly more prevalent during M. canettii infection than during M. tuberculosis infection (1). Also, M. canettii was reported to cause esophageal tuberculosis (14), mesenteric lymph node tuberculosis (15), and ascites (16), and several isolates have been cultured in gastric fluid (14). These clinical observations led to our hypothesis that the digestive tract is a possible portal of entry of M. canettii (1).…”

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confidence: 95%

Ready Experimental Translocation of Mycobacterium canettii Yields Pulmonary Tuberculosis

et al. 2017

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Mycobacterium canettii, which has a smooth colony morphology, is the tuberculous organism retaining the most genetic traits from the putative last common ancestor of the rough-morphology Mycobacterium tuberculosis complex. To explore whether M. canettii can infect individuals by the oral route, mice were fed phosphate-buffered saline or 10 6 M. canettii mycobacteria and sacrificed over a 28-day experiment. While no M. canettii was detected in negative controls, M. canettiiinfected mice yielded granuloma-like lesions for 4/4 lungs at days 14 and 28 postinoculation (p.i.) and positive PCR detection of M. canettii for 5/8 mesenteric lymph nodes at days 1 and 3 p.i. and 5/6 pooled stools collected from day 1 to day 28 p.i. Smooth M. canettii colonies grew from 68% of lungs and 36% of spleens and cervical lymph nodes but fewer than 20% of axillary lymph nodes, livers, brown fat samples, kidneys, or blood samples throughout the 28-day experiment. Ready translocation in mice after digestive tract challenge demonstrates the potential of ingested M. canettii organisms to relocate to distant organs and lungs. The demonstration of this relocation supports the possibility that populations may be infected by environmental M. canettii.

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Progenitor “Mycobacterium canettii” Clone Responsible for Lymph Node Tuberculosis Epidemic, Djibouti

Abstract: Two outbreaks among expatriate children were caused by an epidemic clone from the Horn of Africa.

Cited by 63 publications

References 24 publications

Key experimental evidence of chromosomal DNA transfer among selected tuberculosis-causing mycobacteria

Key experimental evidence of chromosomal DNA transfer among selected tuberculosis-causing mycobacteria

Consequences of genomic diversity in Mycobacterium tuberculosis

Ready Experimental Translocation of Mycobacterium canettii Yields Pulmonary Tuberculosis

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