Metagenomics of Imported Multidrug-Resistant Mycobacterium leprae, Saudi Arabia, 2017.
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ABSTRACT:
SUBMITTER: Guan Q
PROVIDER: S-EPMC7045828 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Sequences of the folP1, rpoB, and gyrA genes were analyzed for 88 isolates of Mycobacterium leprae from leprosy patients in Japan, Haiti, Indonesia, Pakistan, and the Philippines. Thirteen isolates (14.8%) showed representative mutations in more than two genes, suggesting the emergence of multidrug-resistant M. leprae.
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Project description:Background:In Saudi Arabia, cross-border transmission of multidrug-resistant (MDR) Mycobacterium tuberculosis complex (MTBC) strains might be particularly fostered by high immigration rates. Herein, we aimed to elucidate the transmission dynamics of MDR-MTBC strains and reveal a detailed prediction of all resistance-conferring mutations for the first- and second-line drugs. Methods:We investigated all MDR-MTBC strains collected between 2015 and 2017 from provincial mycobacteria referral laboratories and compared demographic and clinical parameters to a cohort of non-MDR-TB patients using a whole genome sequencing approach. Clusters were defined based on a maximum strain-to-strain genetic distance of five single-nucleotide polymorphisms (SNPs) as surrogate marker for recent transmission, and then investigated molecular drug-resistance markers (37 genes). Results:Forty-eight (67.6%) MDR-MTBC strains were grouped in 14 different clusters, ranging in size from two to six strains; 22.5% (16/71) of all MDR-MTBC isolates were predicted to be fully resistant to all five first-line drugs, and five strains (7.0%) exhibited fluoroquinolone resistance. Moreover, we revealed the presence of 12 compensatory mutations as well as 26 non-synonymous SNPs in the rpoC gene and non-hotspot region in rpoB, respectively. Conclusion:Optimized TB molecular surveillance, diagnosis, and patient management are urgently needed to contain MDR-MTBC transmission and prevent the development of additional drug resistance.
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Project description:BackgroundThe phylogeographical structure of Mycobacterium tuberculosis is generally bimodal in low tuberculosis (TB) incidence countries, where genetic lineages of the isolates generally differ with little strain clustering between autochthonous and foreign-born TB patients. However, less is known on this structure in Saudi Arabia-the most important hub of human migration as it hosts a total population of expatriates and pilgrims from all over the world which is equal to that of its citizens.MethodologyWe explored the mycobacterial phylogenetic structure and strain molecular clustering in Saudi Arabia by genotyping 322 drug-resistant clinical isolates collected over a 12-month period in a national drug surveillance survey, using 24 locus-based MIRU-VNTR typing and spoligotyping.Principal findingsIn contrast to the cosmopolitan population of the country, almost all the known phylogeographic lineages of M. tuberculosis complex (with noticeable exception of Mycobacterium africanum/West-African 1 and 2) were detected, with Delhi/CAS (21.1%), EAI (11.2%), Beijing (11.2%) and main branches of the Euro-American super-lineage such as Ghana (14.9%), Haarlem (10.6%) and Cameroon (7.8%) being represented. Statistically significant associations of strain lineages were observed with poly-drug resistance and multi drug resistance especially among previously treated cases (p value of <?=?0.001 for both types of resistance), with relative over-representation of Beijing strains in the latter category. However, there was no significant difference among Saudi and non-Saudi TB patients regarding distribution of phylogenetic lineages (p?=?0.311). Moreover, 59.5% (22/37) of the strain molecular clusters were shared between the Saudi born and immigrant TB patients.ConclusionsSpecific distribution of M. tuberculosis phylogeographic lineages is not observed between the autochthonous and foreign-born populations. These observations might reflect both socially favored ongoing TB transmission between the two population groups, and historically deep-rooted, prolonged contacts and trade relations of the peninsula with other world regions. More vigorous surveillance and strict adherence to tuberculosis control policies are urgently needed in the country.
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Project description:Metagenomics study of an Imported Multidrug-Resistant Mycobacterium leprae, Saudi Arabia, 2017
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Project description:BACKGROUND:Leprosy has been treated with multidrug therapy, which has been distributed for free across the globe and regarded as highly efficient. However, the impossibility of growing Mycobacterium leprae in axenic media has historically impaired assessments of M. leprae resistance, a parameter only recently detectable through molecular methods. METHODS:A systematic, population-based search for M. leprae resistance in suspected leprosy relapse cases and contacts was performed in Prata Village, an isolated, hyperendemic, former leprosy colony located in the Brazilian Amazon. Results led to an extended active search involving the entire Prata population. Confirmed leprosy cases were investigated for bacterial resistance using a combination of in vivo testing and direct sequencing of resistance genes folP1, rpoB, and gyrA. A molecular epidemiology analysis was performed using data from 17 variable number tandem repeats (VNTR). RESULTS:Mycobacterium leprae was obtained from biopsies of 37 leprosy cases (18 relapses and 19 new cases): 16 (43.24%) displayed drug-resistance variants. Multidrug resistance to rifampicin and dapsone was observed in 8 relapses and 4 new cases. Single resistance to rifampicin was detected in 1 new case. Resistance to dapsone was present in 2 relapses and 1 new case. Combined molecular resistance and VNTR data revealed evidence of intra-familial primary transmission of resistant M. leprae. CONCLUSIONS:A comprehensive, population-based systematic approach to investigate M. leprae resistance in a unique population revealed an alarming scenario of the emergence and transmission of resistant strains. These findings may be used for the development of new strategies for surveillance of drug resistance in other populations.
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