Microevolution, reinfection and highly complex genomic diversity in patients with sequential isolates of Mycobacterium abscessus

Sergio Buenestado-Serrano, Miguel Martínez-Lirola, Marta Herranz-Martín, Jaime Esteban, Antonio Broncano-Lavado, Andrea Molero-Salinas, Amadeo Sanz-Pérez, Jesús Blázquez, Alba Ruedas-López, Carlos Toro, Paula López-Roa, Diego Domingo, Ester Zamarrón, María Jesús Ruiz Serrano, Patricia Muñoz, Laura Pérez-Lago () and Darío García de Viedma ()
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Sergio Buenestado-Serrano: Hospital General Universitario Gregorio Marañón
Miguel Martínez-Lirola: Hospital Universitario Torrecárdenas
Marta Herranz-Martín: Hospital General Universitario Gregorio Marañón
Jaime Esteban: Hospital Universitario La Fundación Jiménez Díaz
Antonio Broncano-Lavado: Hospital Universitario La Fundación Jiménez Díaz
Andrea Molero-Salinas: Hospital General Universitario Gregorio Marañón
Amadeo Sanz-Pérez: Hospital General Universitario Gregorio Marañón
Jesús Blázquez: Campus de la Universidad Autónoma-Cantoblanco
Alba Ruedas-López: Hospital Universitario 12 de Octubre
Carlos Toro: Hospital Universitario La Paz - IdiPAZ
Paula López-Roa: Hospital Universitario 12 de Octubre
Diego Domingo: Instituto de Investigación Sanitaria, Hospital Universitario La Princesa
Ester Zamarrón: Hospital Universitario La Paz -IdiPAZ
María Jesús Ruiz Serrano: Hospital General Universitario Gregorio Marañón
Patricia Muñoz: Hospital General Universitario Gregorio Marañón
Laura Pérez-Lago: Hospital General Universitario Gregorio Marañón
Darío García de Viedma: Hospital General Universitario Gregorio Marañón

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract Mycobacterium abscessus is an opportunistic, extensively drug-resistant non-tuberculous mycobacterium. Few genomic studies consider its diversity in persistent infections. Our aim was to characterize microevolution/reinfection events in persistent infections. Fifty-three sequential isolates from 14 patients were sequenced to determine SNV-based distances, assign resistance mutations and characterize plasmids. Genomic analysis revealed 12 persistent cases (0-13 differential SNVs), one reinfection (15,956 SNVs) and one very complex case (23 sequential isolates over 192 months), in which a first period of persistence (58 months) involving the same genotype 1 was followed by identification of a genotype 2 (76 SNVs) in 6 additional alternating isolates; additionally, ten transient genotypes (88-243 SNVs) were found. A macrolide resistance mutation was identified from the second isolate. Despite high diversity, the genotypes shared a common phylogenetic ancestor and some coexisted in the same specimens. Genomic analysis is required to access the true intra-patient complexity behind persistent infections involving M. abscessus.

Date: 2024
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DOI: 10.1038/s41467-024-46552-w

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