Detection of<i>Mycobacterium leprae</i>DNA in soil; Multiple needles in the haystack?

Tió-Coma, Maria; Wijnands, Thomas; Pierneef, Louise; Schilling, Anna‐Katarina; Alam, Korshed; Roy, Johan Chandra; Faber, William R.; Menke, Henk E.; Pieters, Toine; Stevenson, Karen; Richardus, Jan Hendrik; Geluk, Annemieke

doi:10.1101/367219

Cited by 3 publications

(4 citation statements)

References 27 publications

(32 reference statements)

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“…We also hypothesize that the presence of a degradation pathway of dichlorobenzene in M. leprae suggests that the bacterium is able to survive in non-host environments by exploiting other carbon sources. This is consistent with previous studies (54,55), which showed that the presence of viable M. leprae in soil samples is suggestive of environmental reservoirs of the bacteria. The authors, therefore, provided an explanation for the occurrence of leprosy from individuals living in areas where human leprosy cases were not previously reported; this suggests that M. leprae might not really be an obligate parasite.…”

Section: Psi-blast Of Mtbsupporting

confidence: 93%

Analysis of metabolic pathways in mycobacteria to aid drug-target identification

Bannerman

Vedithi

Júlvez

et al. 2019

Preprint

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Full Title: Comparative analyses of metabolic pathways in mycobacteria: Insights into the identification and characterisation of new drug targets in M. tuberculosis, M. leprae and M. abscessus Abstract Three related mycobacteria are the cause of widespread infections in man and are the focus of intense research and drug-discovery efforts in the face of growing antimicrobial resistance.Mycobacterium tuberculosis, the causative agent of tuberculosis, is currently one of the top ten causes of death in the world according to WHO; M. abscessus, a group of non-tuberculous mycobacteria causes lung infections and other opportunistic infections in humans; and M. leprae, the causative agent of leprosy, remains endemic in tropical countries. There is an urgent need to design alternatives to conventional treatment strategies, due to the increase in resistance to standard antibacterials. In this study, we present a comparative analysis of chokepoint and essentiality datasets that will provide insight into the development of new treatment regimes. We illustrate the key metabolic pathways shared between these three organisms and identify drug targets with a wide metabolic impact that are common to the three species. We demonstrate that 72% of the chokepoint enzymes are proteins essential to Mycobacterium tuberculosis. We show also that 78% of the drug targets, prioritized based on their presence in multiple paths on the metabolic network, are present in pathways shared by M. tuberculosis, M. leprae and M. abscessus, including biosynthesis of amino acids, carbohydrates, cell structures, fatty acid and lipid biosynthesis. A further 17% is found in the prioritised pathways shared between M. tuberculosis and M. abscessus. We have performed comparative structure modelling of potential drug targets identified using our analysis in order to assess druggability and demonstrate the importance of chokepoint analysis in terms of drug target identification. AUTHOR SUMMARYComputer simulation studies to design new drugs against mycobacteria

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Section: Psi-blast Of Mtbsupporting

confidence: 93%

Analysis of metabolic pathways in mycobacteria to aid drug-target identification

Bannerman

Vedithi

Júlvez

et al. 2019

Preprint

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“…The limited variation observed in the M. leprae genome permits the reconstruction of historic human migration patterns and the origin of M. leprae (28). Over the years, several studies have contributed to the detection and characterization of M. leprae genomes originating from patients all around the world (21,22,29) as well as from ancient skeletons (30)(31)(32)(33)(34), red squirrels (2,7,35), armadillos (3,4), non-human primates (5) and soil (36)(37)(38)(39)(40)(41)(42). Moreover, skeleton remains have been successfully applied to retrospectively assess whether individuals who contributed to the care of leprosy patients such as the priest Petrus Donders, had developed leprosy (43).…”

Section: Leprae Is Closely Related Tomentioning

confidence: 99%

“…RLEP PCR (23) was performed as previously described (36). Briefly, the 129 bp RLEP sequence was Samples from index cases and a selectin of contacts for sequencing were also evaluated by qPCR (72).…”

Section: Rlep Pcr and Qpcrmentioning

confidence: 99%

Detection of new Mycobacterium leprae subtype in Bangladesh by genomic characterization to explore transmission patterns

Tió-Coma

Avanzi

Verhard

et al. 2020

Preprint

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Mycobacterium leprae, the causative agent of leprosy, is an unculturable bacterium with a considerably reduced genome (3.27 Mb) compared to homologues mycobacteria from the same ancestry. M. leprae transmission is suggested to occur through aerosols but the exact mechanisms of infection remains unclear. In 2001, the genome of M. leprae was first described and subsequently four genotypes (1-4) and 16 subtypes (A-P) were identified providing means to study global transmission patterns for leprosy. We investigated M. leprae carriage as well as infection in leprosy patients (n=60) and healthy household contacts (HHC; n=250) from Bangladesh using molecular detection of the bacterial element RLEP in nasal swabs (NS) and slit skin smears (SSS). In parallel, we explored bacterial strain diversity by whole-genome sequencing (WGS) and Sanger sequencing. In the studied cohort in Bangladesh, M. leprae DNA was detected in 33.3% of NS and 22.2% of SSS of patients with bacillary index of 0 whilst in HHC 18.0% of NS and 12.3% of SSS were positive. The majority of the M. leprae strains detected in this study belonged to genotype 1D (55%), followed by 1A (31%). Importantly, WGS allowed the identification of a new M. leprae genotype, designated 1B-Bangladesh (14%), which clustered separately between the 1A and 1B strains. Moreover, we established that the genotype previously designated 1C, is not an independent subtype but clusters within the 1D genotype. Intraindividual differences were present between the M. leprae strains obtained including mutations in hypermutated genes, suggesting mixed colonization/infection or in-host evolution. In summary, we observed that M. leprae is present in asymptomatic contacts of leprosy patients fueling the concept that these individuals contribute to the current intensity of transmission. Our data therefore emphasize the importance of sensitive and specific tools allowing post-exposure prophylaxis targeted at M. leprae-infected or -colonized individuals.

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“…Transmission is unabated as shown by stable numbers of new cases worldwide (WHO, ). Close contact to multibacillary patients (Moet, Meima, Oskam, & Richardus, ), and, to a lesser extent, infected animals and environmental sources are presumed to play a role in transmission (Tió‐Coma et al, ; Truman et al, ).…”

Section: Introductionmentioning

confidence: 99%

Lack of evidence for the presence of leprosy bacilli in red squirrels from North‐West Europe

Tió-Coma

Sprong

Kik

et al. 2019

Transbound Emerg Dis

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Leprosy is a human infectious disease caused by Mycobacterium leprae or Mycobacterium lepromatosis that can also occur in animals and even manifest as zoonosis. Recently, both mycobacteria were detected in red squirrels (Sciurus vulgaris) from the British Isles. To further explore the presence of leprosy bacilli in North‐West Europe, we screened Belgian and Dutch squirrels. Tissue samples from 115 animals tested by qPCR were negative for both pathogens. No molecular or pathological evidence was found of the presence of these zoonotic pathogens in North‐West Europe.

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Detection ofMycobacterium lepraeDNA in soil; Multiple needles in the haystack?

Cited by 3 publications

References 27 publications

Analysis of metabolic pathways in mycobacteria to aid drug-target identification

Analysis of metabolic pathways in mycobacteria to aid drug-target identification

Detection of new Mycobacterium leprae subtype in Bangladesh by genomic characterization to explore transmission patterns

Lack of evidence for the presence of leprosy bacilli in red squirrels from North‐West Europe

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