RESUMO
The study of the microbiome has changed our overall perspective on health and disease. Although studies of the lung microbiome have lagged behind those on the gastrointestinal microbiome, there is now evidence that the lung microbiome is a rich, dynamic ecosystem. Tuberculosis is one of the oldest human diseases, it is primarily a respiratory infectious disease caused by strains from the Mycobacterium tuberculosis Complex. Even today, during the COVID-19 pandemic, it remains one of the principal causes of morbidity and mortality worldwide. Tuberculosis disease manifests itself as a dynamic spectrum that ranges from asymptomatic latent infection to life-threatening active disease. The review aims to provide an overview of the microbiome in the tuberculosis setting, both in patients' and animal models. We discuss the relevance of the microbiome and its dysbiosis, and how, probably through its interaction with the immune system, it is a significant factor in tuberculosis's susceptibility, establishment, and severity.
RESUMO
Whole genome sequencing (WGS) has been proposed as a tool for the diagnosis of drug resistance in tuberculosis (TB); however, there have been few studies on its effectiveness in countries with significantly high drug resistance rates. This study therefore aimed to evaluate the effectiveness of WGS to identify mutations related to drug resistance in TB isolates from an endemic region of Mexico. The results showed that, of 35 multidrug-resistant isolates analyzed, the values of congruence found between the phenotypic drug susceptibility testing and polymorphisms were 94% for isoniazid, 97% for rifampicin, 90% for ethambutol, and 82% for pyrazinamide. It was also possible to identify eight isolates as potential pre-extensive drug resistant (XDR) and one as XDR. Twenty nine isolates were classified within L4 and two transmission clusters were identified. The results show the potential utility of WGS for predicting resistance against first- and second-line drugs, as well as providing a phylogenetic characterization of TB drug-resistant isolates circulating in Mexico.
Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Extensivamente Resistente a Medicamentos/genética , Humanos , México/epidemiologia , Testes de Sensibilidade Microbiana , Fenótipo , Polimorfismo Genético , Sequenciamento Completo do GenomaRESUMO
Staphylococcus epidermidis is a human commensal and pathogen worldwide distributed. In this work, we surveyed for multi-resistant S. epidermidis strains in eight years at a children's health-care unit in México City. Multidrug-resistant S. epidermidis were present in all years of the study, including resistance to methicillin, beta-lactams, fluoroquinolones, and macrolides. To understand the genetic basis of antibiotic resistance and its association with virulence and gene exchange, we sequenced the genomes of 17 S. epidermidis isolates. Whole-genome nucleotide identities between all the pairs of S. epidermidis strains were about 97% to 99%. We inferred a clonal structure and eight Multilocus Sequence Types (MLSTs) in the S. epidermidis sequenced collection. The profile of virulence includes genes involved in biofilm formation and phenol-soluble modulins (PSMs). Half of the S. epidermidis analyzed lacked the ica operon for biofilm formation. Likely, they are commensal S. epidermidis strains but multi-antibiotic resistant. Uneven distribution of insertion sequences, phages, and CRISPR-Cas immunity phage systems suggest frequent horizontal gene transfer. Rates of recombination between S. epidermidis strains were more prevalent than the mutation rate and affected the whole genome. Therefore, the multidrug resistance, independently of the pathogenic traits, might explain the persistence of specific highly adapted S. epidermidis clonal lineages in nosocomial settings.
RESUMO
BACKGROUND: Whole genome sequencing (WGS) has been proposed as a tool for diagnosing drug resistance in tuberculosis. However, reports of its effectiveness in endemic countries with important numbers of drug resistance are scarce. The goal of this study was to evaluate the effectiveness of this procedure in isolates from a tuberculosis endemic region in Mexico. METHODS: WGS analysis was performed in 81 tuberculosis positive clinical isolates with a known phenotypic profile of resistance against first-line drugs (isoniazid, rifampin, ethambutol, pyrazinamide and streptomycin). Mutations related to drug resistance were identified for each isolate; drug resistant genotypes were predicted and compared with the phenotypic profile. Genotypes and transmission clusters based on genetic distances were also characterized. FINDINGS: Prediction by WGS analysis of resistance against isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin showed sensitivity values of 84%, 96%, 71%, 75% and 29%, while specificity values were 100%, 94%, 90%, 90% and 98%, respectively. Prediction of multidrug resistance showed a sensitivity of 89% and specificity of 97%. Moreover, WGS analysis revealed polymorphisms related to second-line drug resistance, enabling classification of eight and two clinical isolates as pre- and extreme drug-resistant cases, respectively. Lastly, four lineages were identified in the population (L1, L2, L3 and L4). The most frequent of these was L4, which included 90% (77) of the isolates. Six transmission clusters were identified; the most frequent was TC6, which included 13 isolates with a L4.1.1 and a predominantly multidrug-resistant condition. CONCLUSIONS: The results illustrate the utility of WGS for establishing the potential for prediction of resistance against first and second line drugs in isolates of tuberculosis from the region. They also demonstrate the feasibility of this procedure for use as a tool to support the epidemiological surveillance of drug- and multidrug-resistant tuberculosis.