Genomic diversity and resistance profile of Mycobacterium avium clinical strains circulating in Portugal between 2018 and 2022

Detalhes bibliográficos
Autor(a) principal: Rodrigues, Joana
Data de Publicação: 2024
Outros Autores: Rodrigues, Irene, Carneiro, Sofia, Silva, Sónia, Santos, Andrea, Macedo, Rita
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://doi.org/10.25761/anaisihmt.453
Resumo: Introduction: In recent years, opportunistic infections with nontuberculous mycobacteria (NTM) have gained increasing importance in public health, with Mycobacterium avium being the most responsible species for the increase of human disease cases. These infections manifest mainly at the respiratory level, and disseminated infection may also occur, especially in immunocompromised individuals. Currently, the mode of transmission is not established, but environmental exposure is considered the main source of infection. Therefore, epidemiological studies are essential to identify possible foci of infection, and thus improve methods of surveillance, prevention, and control of this type of disease. Objective: Evaluation of the genomic diversity and resistance profile of clinical isolates of Mycobacterium avium circulating in Portugal between 2018 and 2022. Methods: Between 2018 and 2022, the National Reference Laboratory for Mycobacteria (LNR-TB), at INSA received 103 M. avium isolates. Of these, a subset of 42 strains was characterized for genomic diversity using the MIRUVNTR molecular typing methodology. Additionally, 40 (95%) strains were tested for phenotypic susceptibility to clarithromycin, moxifloxacin, and linezolid, and molecular susceptibility, by screening of mutations in the 16S rRNA (rrs) and 23S rRNA (rrl) genes associated with resistance to aminoglycosides and macrolides, respectively. Results: Phenotypic susceptibility testing indicated that 98% (39) of the strains were susceptible to clarithromycin, while only 25% (n=10) and 27.5% (n=11) were susceptible to linezolid and moxifloxacin. There was a high correlation between the results of phenotypic and genotypic susceptibility testing with respect to macrolides. MIRU-VNTR genotyping revealed a high genetic diversity among the strains. Using a threshold of 1 locus and 2 loci between strains, it was observed two molecular clusters and 37 singletons and eight clusters and 20 singletons, respectively. Overall, the MIRU-VNTR methodology allowed a discriminatory power of 0.9988. Conclusion: Although molecular clusters were detected, the analysis of MIRU-VNTR profiles is insufficient to establish concrete epidemiological relationships. In addition to patient demographics, clinical data is needed, which may require consideration of a mandatory reporting system for more assertive laboratory surveillance of M. avium disease.
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spelling Genomic diversity and resistance profile of Mycobacterium avium clinical strains circulating in Portugal between 2018 and 2022Diversité génomique et profil de résistance des isolats cliniques de Mycobacterium avium circulant au Portugal entre 2018 et 2022Diversidade genómica e perfil de resistência dos isolados clínicos de Mycobacterium avium circulantes em Portugal entre 2018 e 2022Introduction: In recent years, opportunistic infections with nontuberculous mycobacteria (NTM) have gained increasing importance in public health, with Mycobacterium avium being the most responsible species for the increase of human disease cases. These infections manifest mainly at the respiratory level, and disseminated infection may also occur, especially in immunocompromised individuals. Currently, the mode of transmission is not established, but environmental exposure is considered the main source of infection. Therefore, epidemiological studies are essential to identify possible foci of infection, and thus improve methods of surveillance, prevention, and control of this type of disease. Objective: Evaluation of the genomic diversity and resistance profile of clinical isolates of Mycobacterium avium circulating in Portugal between 2018 and 2022. Methods: Between 2018 and 2022, the National Reference Laboratory for Mycobacteria (LNR-TB), at INSA received 103 M. avium isolates. Of these, a subset of 42 strains was characterized for genomic diversity using the MIRUVNTR molecular typing methodology. Additionally, 40 (95%) strains were tested for phenotypic susceptibility to clarithromycin, moxifloxacin, and linezolid, and molecular susceptibility, by screening of mutations in the 16S rRNA (rrs) and 23S rRNA (rrl) genes associated with resistance to aminoglycosides and macrolides, respectively. Results: Phenotypic susceptibility testing indicated that 98% (39) of the strains were susceptible to clarithromycin, while only 25% (n=10) and 27.5% (n=11) were susceptible to linezolid and moxifloxacin. There was a high correlation between the results of phenotypic and genotypic susceptibility testing with respect to macrolides. MIRU-VNTR genotyping revealed a high genetic diversity among the strains. Using a threshold of 1 locus and 2 loci between strains, it was observed two molecular clusters and 37 singletons and eight clusters and 20 singletons, respectively. Overall, the MIRU-VNTR methodology allowed a discriminatory power of 0.9988. Conclusion: Although molecular clusters were detected, the analysis of MIRU-VNTR profiles is insufficient to establish concrete epidemiological relationships. In addition to patient demographics, clinical data is needed, which may require consideration of a mandatory reporting system for more assertive laboratory surveillance of M. avium disease.Introduction: Ces dernières années, les infections opportunistes par les mycobactéries non tuberculeuses (MNT) ont pris de l’importance pour la santé publique, Mycobacterium avium étant l’espèce la plus responsable de l’augmentation des cas de maladie chez l’homme. Actuellement, le mode de transmission n’est pas établi, mais l’exposition environnementale est considérée comme la principale source d’infection. Ainsi, des études épidémiologiques sont essentiels pour identifier les foyers d’infection potentiels et améliorer les méthodes de surveillance, de prévention et de contrôle de cette maladie. Objectif de l’étude: Évaluation de la diversité génomique et du profil de résistance des isolats cliniques de Mycobacterium avium circulant au Portugal entre 2018 et 2022. Méthodes: Entre 2018 et 2022, le Laboratoire National de Référence pour les Mycobactéries (LNR-TB) de l’INSA a reçu 103 isolats de M. avium. Parmi eux, un sous-ensemble de 42 souches a été caractérisé quant à leur diversité génomique grâce à la méthode de typage moléculaire MIRUVNTR. De plus, des tests de susceptibilité phénotypique à la clarithromycine, à la moxifloxacine et au linézolide ont été réalisés sur 40 (95%) souches, ainsi que des tests de susceptibilité moléculaire en recherchant des mutations dans les gènes 16S rRNA (rrs) et 23S rRNA (rrl) associées à la résistance aux aminoglycosides (AG) et aux macrolides, respectivement. Résultats: Les tests de susceptibilité phénotypique ont montré que 98% (39) des souches étaient sensibles à la clarithromycine, tandis qu’une faible proportion (25% et 27,5%) était sensible au linézolide et à la moxifloxacine. Une corrélation significative entre les résultats phénotypiques et génotypiques a été observée pour les macrolides. La méthode de typage moléculaire MIRU-VNTR a révélé une grande diversité génétique entre les souches, avec un indice discriminatoire de 0.9988. Ces résultats soulignent l’importance d’une surveillance continue des isolats cliniques de Mycobacterium avium pour mieux comprendre la résistance et améliorer les stratégies de gestion de cette maladie. Conclusion: Bien que des groupes moléculaires aient été trouvés, l’analyse des profils MIRU-VNTR est insuffisante pour établir des relations épidémiologiques concrètes. Outre les données démographiques des patients, des données cliniques sont nécessaires, ce qui pourrait nécessiter une surveillance de laboratoire plus fiable de la maladie de M. avium.Introdução: Nos últimos anos, infeções oportunistas por micobactérias não tuberculosas (MNT), têm ganho uma importância crescente na saúde pública, sendo a espécie Mycobacterium avium, a principal responsável pelo aumento de casos de doença humana. Estas infeções manifestam-se principalmente a nível respiratório podendo também ocorrer, sobretudo em indivíduos imunocomprometidos, infeção disseminada. Atualmente, o modo de transmissão não está estabelecido, contudo, a exposição ambiental é considerada a principal fonte de infeção. Assim, é essencial a realização de estudos epidemiológicos para identificar possíveis focos de infeção e, deste modo, melhorar os métodos de vigilância, prevenção e controlo da doença. Objetivo: Avaliação da diversidade genómica e perfil de resistência de isolados clínicos de Mycobacterium avium circulantes em Portugal entre 2018 e 2022. Métodos: Um conjunto de 42 estirpes de M. avium, isoladas entre 2018 e 2022, no Laboratório Nacional de Referência para Micobactérias (LNR-TB) do INSA, foi caracterizado quanto à sua diversidade genómica através da metodologia de tipagem molecular MIRU-VNTR. Adicionalmente, foram realizados testes de suscetibilidade fenotípica à claritromicina, moxifloxacina e linezolide em 40 (95%) estirpes e de suscetibilidade molecular por pesquisa de mutações nos genes 16S rRNA (rrs) e 23S rRNA (rrl), associados a resistência a aminoglicosídeos (AG) e macrólidos, respetivamente. Resultados: Os testes de suscetibilidade fenotípica indicaram que 98% (39) das estirpes foram suscetíveis à claritromicina, enquanto apenas 25% (n=10) e 27,5% (n=11) foram suscetíveis ao linezolide e moxifloxacina. Verificou-se uma elevada correlação entre os resultados de testes de suscetibilidade fenotípica e genotípica relativamente aos macrólidos. A genotipagem por MIRU-VNTR revelou uma grande diversidade genética entre as estirpes. Usando threshold de 1 locus e 2 loci de permissão de diferença entre as estirpes, observou-se o agrupamento de dois clusters moleculares e 37 singletons e oito clusters e 20 singletons, respetivamente. No global, a metodologia MIRU-VNTR obteve um índice discriminatório de 0.9988. Conclusão: Embora tenham sido detetados clusters mo- leculares, a análise dos perfis MIRU-VNTR é insuficiente para estabelecer relações epidemiológicas concretas. Para além dos dados demográficos dos doentes são necessários dados clínicos, o que pode requerer a ponderação de um sistema de notificação obrigatória para uma vigilância laboratorial da doença por M. avium mais assertiva.Universidade Nova de Lisboa2024-01-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://doi.org/10.25761/anaisihmt.453https://doi.org/10.25761/anaisihmt.453Anais do Instituto de Higiene e Medicina Tropical; Vol 22 No 2 (2023): Medicina Tropical e Desenvolvimento Sustentável - 6.º Congresso Nacional de Medicina Tropical; 22-32Anais do Instituto de Higiene e Medicina Tropical; v. 22 n. 2 (2023): Medicina Tropical e Desenvolvimento Sustentável - 6.º Congresso Nacional de Medicina Tropical; 22-322184-23100303-7762reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAPporhttp://anaisihmt.com/index.php/ihmt/article/view/453http://anaisihmt.com/index.php/ihmt/article/view/453/375Direitos de Autor (c) 2024 Anais do Instituto de Higiene e Medicina Tropicalhttp://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessRodrigues, JoanaRodrigues, IreneCarneiro, SofiaSilva, SóniaSantos, AndreaMacedo, Rita2024-02-21T21:32:53Zoai:ojs.anaisihmt.com:article/453Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:38:14.097993Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Genomic diversity and resistance profile of Mycobacterium avium clinical strains circulating in Portugal between 2018 and 2022
Diversité génomique et profil de résistance des isolats cliniques de Mycobacterium avium circulant au Portugal entre 2018 et 2022
Diversidade genómica e perfil de resistência dos isolados clínicos de Mycobacterium avium circulantes em Portugal entre 2018 e 2022
title Genomic diversity and resistance profile of Mycobacterium avium clinical strains circulating in Portugal between 2018 and 2022
spellingShingle Genomic diversity and resistance profile of Mycobacterium avium clinical strains circulating in Portugal between 2018 and 2022
Rodrigues, Joana
title_short Genomic diversity and resistance profile of Mycobacterium avium clinical strains circulating in Portugal between 2018 and 2022
title_full Genomic diversity and resistance profile of Mycobacterium avium clinical strains circulating in Portugal between 2018 and 2022
title_fullStr Genomic diversity and resistance profile of Mycobacterium avium clinical strains circulating in Portugal between 2018 and 2022
title_full_unstemmed Genomic diversity and resistance profile of Mycobacterium avium clinical strains circulating in Portugal between 2018 and 2022
title_sort Genomic diversity and resistance profile of Mycobacterium avium clinical strains circulating in Portugal between 2018 and 2022
author Rodrigues, Joana
author_facet Rodrigues, Joana
Rodrigues, Irene
Carneiro, Sofia
Silva, Sónia
Santos, Andrea
Macedo, Rita
author_role author
author2 Rodrigues, Irene
Carneiro, Sofia
Silva, Sónia
Santos, Andrea
Macedo, Rita
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Rodrigues, Joana
Rodrigues, Irene
Carneiro, Sofia
Silva, Sónia
Santos, Andrea
Macedo, Rita
description Introduction: In recent years, opportunistic infections with nontuberculous mycobacteria (NTM) have gained increasing importance in public health, with Mycobacterium avium being the most responsible species for the increase of human disease cases. These infections manifest mainly at the respiratory level, and disseminated infection may also occur, especially in immunocompromised individuals. Currently, the mode of transmission is not established, but environmental exposure is considered the main source of infection. Therefore, epidemiological studies are essential to identify possible foci of infection, and thus improve methods of surveillance, prevention, and control of this type of disease. Objective: Evaluation of the genomic diversity and resistance profile of clinical isolates of Mycobacterium avium circulating in Portugal between 2018 and 2022. Methods: Between 2018 and 2022, the National Reference Laboratory for Mycobacteria (LNR-TB), at INSA received 103 M. avium isolates. Of these, a subset of 42 strains was characterized for genomic diversity using the MIRUVNTR molecular typing methodology. Additionally, 40 (95%) strains were tested for phenotypic susceptibility to clarithromycin, moxifloxacin, and linezolid, and molecular susceptibility, by screening of mutations in the 16S rRNA (rrs) and 23S rRNA (rrl) genes associated with resistance to aminoglycosides and macrolides, respectively. Results: Phenotypic susceptibility testing indicated that 98% (39) of the strains were susceptible to clarithromycin, while only 25% (n=10) and 27.5% (n=11) were susceptible to linezolid and moxifloxacin. There was a high correlation between the results of phenotypic and genotypic susceptibility testing with respect to macrolides. MIRU-VNTR genotyping revealed a high genetic diversity among the strains. Using a threshold of 1 locus and 2 loci between strains, it was observed two molecular clusters and 37 singletons and eight clusters and 20 singletons, respectively. Overall, the MIRU-VNTR methodology allowed a discriminatory power of 0.9988. Conclusion: Although molecular clusters were detected, the analysis of MIRU-VNTR profiles is insufficient to establish concrete epidemiological relationships. In addition to patient demographics, clinical data is needed, which may require consideration of a mandatory reporting system for more assertive laboratory surveillance of M. avium disease.
publishDate 2024
dc.date.none.fl_str_mv 2024-01-31
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dc.identifier.uri.fl_str_mv https://doi.org/10.25761/anaisihmt.453
https://doi.org/10.25761/anaisihmt.453
url https://doi.org/10.25761/anaisihmt.453
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dc.relation.none.fl_str_mv http://anaisihmt.com/index.php/ihmt/article/view/453
http://anaisihmt.com/index.php/ihmt/article/view/453/375
dc.rights.driver.fl_str_mv Direitos de Autor (c) 2024 Anais do Instituto de Higiene e Medicina Tropical
http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Direitos de Autor (c) 2024 Anais do Instituto de Higiene e Medicina Tropical
http://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Universidade Nova de Lisboa
publisher.none.fl_str_mv Universidade Nova de Lisboa
dc.source.none.fl_str_mv Anais do Instituto de Higiene e Medicina Tropical; Vol 22 No 2 (2023): Medicina Tropical e Desenvolvimento Sustentável - 6.º Congresso Nacional de Medicina Tropical; 22-32
Anais do Instituto de Higiene e Medicina Tropical; v. 22 n. 2 (2023): Medicina Tropical e Desenvolvimento Sustentável - 6.º Congresso Nacional de Medicina Tropical; 22-32
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0303-7762
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