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

Author:

Buenestado-Serrano SergioORCID,Martínez-Lirola Miguel,Herranz-Martín Marta,Esteban JaimeORCID,Broncano-Lavado Antonio,Molero-Salinas Andrea,Sanz-Pérez Amadeo,Blázquez Jesús,Ruedas-López AlbaORCID,Toro Carlos,López-Roa Paula,Domingo Diego,Zamarrón EsterORCID,Ruiz Serrano María Jesús,Muñoz Patricia,Pérez-Lago LauraORCID,García de Viedma DaríoORCID

Abstract

AbstractMycobacterium 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.

Funder

Ministry of Economy and Competitiveness | Instituto de Salud Carlos III

Publisher

Springer Science and Business Media LLC

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