Dataset Information

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

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.

SUBMITTER: Buenestado-Serrano S

PROVIDER: S-EPMC10979023 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Buenestado-Serrano Sergio S Martínez-Lirola Miguel M Herranz-Martín Marta M Esteban Jaime J Broncano-Lavado Antonio A Molero-Salinas Andrea A Sanz-Pérez Amadeo A Blázquez Jesús J Ruedas-López Alba A Toro Carlos C López-Roa Paula P Domingo Diego D Zamarrón Ester E Ruiz Serrano María Jesús MJ Muñoz Patricia P Pérez-Lago Laura L García de Viedma Darío D

Nature communications 20240328 1

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 ...[more]

PMID: 38548737

Similar Datasets

Project description:Members of the Mycobacterium abscessus complex (MABC) are multidrug-resistant nontuberculous mycobacteria and increasingly cause opportunistic pulmonary infections. However, the genetic typing of MABC isolates remains largely unclear in China. Genomic analyses were conducted for 69 MABC clinical isolates obtained from patients with lower respiratory tract infections in Shanghai Pulmonary Hospital between 2014 and 2016. The draft genomes of the 69 clinical strains were assembled, with a total length of 4.5 to 5.6 Mb, a percent GC content (GC%) ranging from 63.9 to 68.1%, and 4,492 to 5,404 genes per genome. Susceptibility test shows that most isolates are resistant to many antimicrobials, including clarithromycin, but susceptible to tigecycline. Analyses revealed the presence of genes conferring resistance to antibiotics, including macrolides, aminoglycosides, rifampicin, and tetracyclines. Furthermore, 80 to 114 virulence genes were identified per genome, including those related to the invasion of macrophages, iron incorporation, and avoidance of immune clearance. Mobile genetic elements, including insertion sequences, transposons, and genomic islands, were discovered in the genomes. Phylogenetic analyses of all MABC isolates with another 41 complete MABC genomes identified three clades; 46 isolates were clustered in clade I, corresponding to M. abscessus subsp. abscessus, and 25 strains belonged to existing clonal complexes. Overall, this is the first comparative genomic analysis of MABC clinical isolates in China. These results show significant intraspecies variations in genetic determinants encoding antimicrobial resistance, virulence, and mobile elements and controversial subspecies classification using current marker gene combinations. This information will be useful in understanding the evolution, antimicrobial resistance, and pathogenesis of MABC strains and facilitating future vaccine development and drug design. IMPORTANCE Over the past decade, infections by Mycobacterium abscessus complex (MABC) isolates have been increasingly reported worldwide. MABC strains often show a high incidence in cystic fibrosis (CF) patients, whereas in Asia, these strains are frequently recovered from non-CF patients with significant genomic diversity. The present work involves analyses of the antimicrobial resistance, virulence, and phylogeny of 69 selected MABC isolates from non-CF pulmonary patients in Shanghai Pulmonary Hospital by whole-genome sequencing; it represents the first comprehensive investigation of MABC strains in China at the genomic level. These findings highlight the diversity of this group of nontuberculous mycobacteria and provide a mechanistic understanding of evolution and pathogenesis, which is valuable for the development of novel and effective antimicrobial therapies for deadly MABC infections in China.

Project description:Mycobacterium abscessus (Mab) is a clinically significant pathogen and a highly genetically diverse species due to its large accessory genome. The functional consequence of this diversity remains unknown mainly because, to date, functional genomic studies in Mab have been primarily performed on reference strains. Given the growing public health threat of Mab infections, understanding the functional genomic differences among Mab clinical isolates can provide more insight into how its genetic diversity influences gene essentiality, clinically relevant phenotypes, and importantly, potential drug targets. To determine the functional genomic diversity among Mab strains, we conducted transposon-sequencing (TnSeq) on 21 genetically diverse clinical isolates, including 15 M. abscessus subsp. abscessus isolates and 6 M. abscessus subsp. massiliense isolates, cataloging all the essential and non-essential genes in each strain. Pan-genome analysis revealed a core set of 3,845 genes and a large accessory genome of 11,507. We identified 259 core essential genes across the 21 clinical isolates and 425 differentially required genes, representing ~10% of the Mab core genome. We also identified genes whose requirements were subspecies, lineage, and isolate-specific. Finally, by correlating TnSeq profiles, we identified 19 previously uncharacterized genetic networks in Mab. Altogether, we find that Mab clinical isolates are not only genetically diverse but functionally diverse as well.ImportanceThis study investigates the genetic diversity of Mycobacterium abscessus (Mab), a bacteria known for causing difficult-to-treat infections. Researchers performed transposon-sequencing (TnSeq) on 21 different clinical isolates of Mab to identify essential and non-essential genes in each strain. Through this analysis, they identified core genes required for growth across all strains. Interestingly, they also identified genes whose requirement for growth or "essentiality" were subspecies, lineage, and isolate-specific. This study reveals that Mab's genetic diversity translates into significant functional differences among clinical isolates. Insights from this paper lay essential groundwork for future studies exploring the biological and clinical implications of genetic diversity in Mab clinical isolates. Understanding this diversity could guide targeted therapies and offer new insights into managing infections caused by Mab, a growing public health concern.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets