Correction: Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas.

[This corrects the article DOI: 10.1371/journal.pntd.0009145.].

Intra-host genetic population diversity: Role in emergence and persistence of drug resistance among Mycobacterium tuberculosis complex minor variants.

Drug resistant tuberculosis (DR-TB) is an important public health issue in different parts of the world. Mycobacterium tuberculosis complex variants (MTBC vars) preferentially infect certain hosts, limiting their distribution to different ecosystems. However, MTBC vars can infect other hosts beyond their preferred target potentially contributing to persistence of drug resistance (DR) in other niches. Here, we performed a comprehensive intra-host genetic analysis for the identification of DR-related mutations among all MTBC minor vars whole genome sequences (8,095 strains) publicly available worldwide. High confidence drug-resistance mutations in katG (isoniazid), rpsL (streptomycin), pncA (pyrazinamide), rpoB (rifampicin) and gyrA (fluoroquinolones) genes were identified among intrahost minor sub-populations in 197 different strains (2.43%) belonging to vars africanum, bovis, caprae, microti, orygis and pinnipedii. In addition, a three-dimensional structure modeling analysis to assess the role of novel mutations was also performed. Our findings highlight the importance of detecting discrete intra-host populations carrying DR mutations.

Identification of drug resistance mutations among Mycobacterium bovis lineages in the Americas.

Identifying the Mycobacterium tuberculosis resistance mutation patterns is of the utmost importance to assure proper patient's management and devising of control programs aimed to limit spread of disease. Zoonotic Mycobacterium bovis infection still represents a threat to human health, particularly in dairy production regions. Routinary, molecular characterization of M. bovis is performed primarily by spoligotyping and mycobacterial interspersed repetitive units (MIRU) while next generation sequencing (NGS) approaches are often performed by reference laboratories. However, spoligotyping and MIRU methodologies lack the resolution required for the fine characterization of tuberculosis isolates, particularly in outbreak settings. In conjunction with sophisticated bioinformatic algorithms, whole genome sequencing (WGS) analysis is becoming the method of choice for advanced genetic characterization of tuberculosis isolates. WGS provides valuable information on drug resistance and compensatory mutations that other technologies cannot assess. Here, we performed an analysis of the most frequently identified mutations associated with tuberculosis drug resistance and their genetic relationship among 2,074 Mycobacterium bovis WGS recovered primarily from non-human hosts. Full-length gene sequences harboring drug resistant associated mutations and their phylogenetic relationships were analyzed. The results showed that M. bovis isolates harbor mutations conferring resistance to both first- and second-line antibiotics. Mutations conferring resistance for isoniazid, fluoroquinolones, streptomycin, and aminoglycosides were identified among animal strains. Our findings highlight the importance of molecular surveillance to monitor the emergence of mutations associated with multi and extensive drug resistance in livestock and other non-human mammals.

Nosocomial transmission of extensively drug resistant Acinetobacter baumannii strains in a tertiary level hospital.

Acinetobacter baumannii is an opportunistic infectious agent that affects primarily immunocompromised individuals. A. baumannii is highly prevalent in hospital settings being commonly associated with nosocomial transmission and drug resistance. Here, we report the identification and genetic characterization of A. baumannii strains among patients in a tertiary level hospital in Mexico. Whole genome sequencing analysis was performed to establish their genetic relationship and drug resistance mutations profile. Ten genetically different, extensively drug resistant strains were identified circulating among seven wards. The genetic profiles showed resistance primarily against aminoglycosides and beta-lactam antibiotics. Importantly, no mutants conferring resistance to colistin were observed. The results highlight the importance of implementing robust classification schemes for advanced genetic characterization of A. baumannii clinical isolates and simultaneous detection of drug resistance markers for adequate patient's management in clinical settings.