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Drug resistant Mycobacterium tuberculosis in Oman: resistance-conferring mutations and lineage diversity

BACKGROUND: The Sultanate of Oman is country a low TB-incidence, with less than seven cases per 10(5) population detected in 2020. Recent years have witnessed a persistence in TB cases, with sustained incidence rate among expatriates and limited reduction among Omanis. This pattern suggests transmis...

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Autores principales: Al Mahrouqi, Sara, Gadalla, Amal, Al Azri, Saleh, Al-Hamidhi, Salama, Al-Jardani, Amina, Balkhair, Abdullah, Al-fahdi, Amira, Al Balushi, Laila, Al Zadjali, Samiya, Al Marhoubi, Asmahan Mohammed Nasser, Babiker, Hamza A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339217/
https://www.ncbi.nlm.nih.gov/pubmed/35919400
http://dx.doi.org/10.7717/peerj.13645
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author Al Mahrouqi, Sara
Gadalla, Amal
Al Azri, Saleh
Al-Hamidhi, Salama
Al-Jardani, Amina
Balkhair, Abdullah
Al-fahdi, Amira
Al Balushi, Laila
Al Zadjali, Samiya
Al Marhoubi, Asmahan Mohammed Nasser
Babiker, Hamza A.
author_facet Al Mahrouqi, Sara
Gadalla, Amal
Al Azri, Saleh
Al-Hamidhi, Salama
Al-Jardani, Amina
Balkhair, Abdullah
Al-fahdi, Amira
Al Balushi, Laila
Al Zadjali, Samiya
Al Marhoubi, Asmahan Mohammed Nasser
Babiker, Hamza A.
author_sort Al Mahrouqi, Sara
collection PubMed
description BACKGROUND: The Sultanate of Oman is country a low TB-incidence, with less than seven cases per 10(5) population detected in 2020. Recent years have witnessed a persistence in TB cases, with sustained incidence rate among expatriates and limited reduction among Omanis. This pattern suggests transmission from the migrant population. The present study examined the genetic profile and drug resistance-conferring mutations in Mycobacterium tuberculosis collected from Omanis and expatriates to recognise possible causes of disease transmission. METHODS: We examined M. tuberculosis cultured positive samples, collected from Omanis (n = 1,344) and expatriates (n = 1,203) between 2009 and 2018. These isolates had a known in vitro susceptibility profile to first line anti-TB, Streptomycin (SM), Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) and Pyrazinamide (PZA). The diversity of the isolates was assessed by spacer oligo-typing (spoligotyping). Drug resistance-conferring mutations resulted from full-length sequence of nine genes (katG, inhA, ahpc, rpoB, rpsL, rrs, embB, embC, pncA) and their phenotypic relationship were analysed. RESULTS: In total, 341/2192 (13.4%), M. tuberculosis strains showed resistance to any drug, comprising mono-resistance (MR) (242, 71%), poly-resistance (PR) (40, 11.7%) and multi-drug resistance (MDR) (59, 17.3%). The overall rate of resistance among Omanis and expatriates was similar; however, MDR and PZA(R) were significantly higher among Omanis, while INH(R) was greater among expatriates. Mutations rpsL K43R and rpoB S450L were linked to Streptomycin (SM(R)) and Rifampicin resistance (RIF(R)) respectively. Whereas, katG S315T and inhA –C15T/G–17T were associated with Isoniazid resistance (INH(R)). The resistance patterns (mono-resistant, poly-resistant and MDR) and drug resistance-conferring mutations were found in different spoligo-lineages. rpsL K43R, katG S315T and rpoB S450L mutations were significantly higher in Beijing strains. CONCLUSIONS: Diverse drug resistant M. tuberculosis strains exist in Oman, with drug resistance-conferring mutations widespread in multiple spoligo-lineages, indicative of a large resistance reservoir. Beijing’s M. tuberculosis lineage was associated with MDR, and multiple drug resistance-conferring mutations, favouring the hypothesis of migration as a possible source of resistant lineages in Oman.
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spelling pubmed-93392172022-08-01 Drug resistant Mycobacterium tuberculosis in Oman: resistance-conferring mutations and lineage diversity Al Mahrouqi, Sara Gadalla, Amal Al Azri, Saleh Al-Hamidhi, Salama Al-Jardani, Amina Balkhair, Abdullah Al-fahdi, Amira Al Balushi, Laila Al Zadjali, Samiya Al Marhoubi, Asmahan Mohammed Nasser Babiker, Hamza A. PeerJ Genetics BACKGROUND: The Sultanate of Oman is country a low TB-incidence, with less than seven cases per 10(5) population detected in 2020. Recent years have witnessed a persistence in TB cases, with sustained incidence rate among expatriates and limited reduction among Omanis. This pattern suggests transmission from the migrant population. The present study examined the genetic profile and drug resistance-conferring mutations in Mycobacterium tuberculosis collected from Omanis and expatriates to recognise possible causes of disease transmission. METHODS: We examined M. tuberculosis cultured positive samples, collected from Omanis (n = 1,344) and expatriates (n = 1,203) between 2009 and 2018. These isolates had a known in vitro susceptibility profile to first line anti-TB, Streptomycin (SM), Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB) and Pyrazinamide (PZA). The diversity of the isolates was assessed by spacer oligo-typing (spoligotyping). Drug resistance-conferring mutations resulted from full-length sequence of nine genes (katG, inhA, ahpc, rpoB, rpsL, rrs, embB, embC, pncA) and their phenotypic relationship were analysed. RESULTS: In total, 341/2192 (13.4%), M. tuberculosis strains showed resistance to any drug, comprising mono-resistance (MR) (242, 71%), poly-resistance (PR) (40, 11.7%) and multi-drug resistance (MDR) (59, 17.3%). The overall rate of resistance among Omanis and expatriates was similar; however, MDR and PZA(R) were significantly higher among Omanis, while INH(R) was greater among expatriates. Mutations rpsL K43R and rpoB S450L were linked to Streptomycin (SM(R)) and Rifampicin resistance (RIF(R)) respectively. Whereas, katG S315T and inhA –C15T/G–17T were associated with Isoniazid resistance (INH(R)). The resistance patterns (mono-resistant, poly-resistant and MDR) and drug resistance-conferring mutations were found in different spoligo-lineages. rpsL K43R, katG S315T and rpoB S450L mutations were significantly higher in Beijing strains. CONCLUSIONS: Diverse drug resistant M. tuberculosis strains exist in Oman, with drug resistance-conferring mutations widespread in multiple spoligo-lineages, indicative of a large resistance reservoir. Beijing’s M. tuberculosis lineage was associated with MDR, and multiple drug resistance-conferring mutations, favouring the hypothesis of migration as a possible source of resistant lineages in Oman. PeerJ Inc. 2022-07-28 /pmc/articles/PMC9339217/ /pubmed/35919400 http://dx.doi.org/10.7717/peerj.13645 Text en ©2022 Al Mahrouqi et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Genetics
Al Mahrouqi, Sara
Gadalla, Amal
Al Azri, Saleh
Al-Hamidhi, Salama
Al-Jardani, Amina
Balkhair, Abdullah
Al-fahdi, Amira
Al Balushi, Laila
Al Zadjali, Samiya
Al Marhoubi, Asmahan Mohammed Nasser
Babiker, Hamza A.
Drug resistant Mycobacterium tuberculosis in Oman: resistance-conferring mutations and lineage diversity
title Drug resistant Mycobacterium tuberculosis in Oman: resistance-conferring mutations and lineage diversity
title_full Drug resistant Mycobacterium tuberculosis in Oman: resistance-conferring mutations and lineage diversity
title_fullStr Drug resistant Mycobacterium tuberculosis in Oman: resistance-conferring mutations and lineage diversity
title_full_unstemmed Drug resistant Mycobacterium tuberculosis in Oman: resistance-conferring mutations and lineage diversity
title_short Drug resistant Mycobacterium tuberculosis in Oman: resistance-conferring mutations and lineage diversity
title_sort drug resistant mycobacterium tuberculosis in oman: resistance-conferring mutations and lineage diversity
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339217/
https://www.ncbi.nlm.nih.gov/pubmed/35919400
http://dx.doi.org/10.7717/peerj.13645
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