Mycobacterium tuberculosis Subculture Results in Loss of Potentially Clinically Relevant Heteroresistance.
Antimicrob Agents Chemother
; 61(11)2017 11.
Article
en En
| MEDLINE
| ID: mdl-28893776
ABSTRACT
Multidrug-resistant tuberculosis (TB) presents a major public health dilemma. Heteroresistance, the coexistence of drug-resistant and drug-susceptible strains or of multiple drug-resistant strains with discrete haplotypes, may affect accurate diagnosis and the institution of effective treatment. Subculture, or passage of cells onto fresh growth medium, is utilized to preserve Mycobacterium tuberculosis cell lines and is universally employed in TB diagnostics. The impact of such passages, typically performed in the absence of drug, on drug-resistant subpopulations is hypothesized to vary according to the competitive costs of genotypic resistance-associated variants. We applied ultradeep next-generation sequencing to 61 phenotypically rifampin-monoresistant (n = 17) and preextensively (n = 41) and extensively (n = 3) drug-resistant isolates with presumptive heteroresistance at two time points in serial subculture. We found significant dynamic loss of minor-variant resistant subpopulations across all analyzed resistance-determining regions, including eight isolates (13%) whose antibiogram data would have transitioned from resistant to susceptible for at least one drug through subculture. Surprisingly, some resistance-associated variants appeared to be selected for in subculture.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tuberculosis Resistente a Múltiples Medicamentos
/
Farmacorresistencia Bacteriana Múltiple
/
Mycobacterium tuberculosis
/
Antituberculosos
Límite:
Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos