title: Differential expression of putative drug resistance genes in Mycobacterium tuberculosis clinical isolates.
abstract: Understanding drug resistance in Mycobacterium tuberculosis requires an integrated analysis of strain lineages, mutations and gene expression. Previously, we reported the differential expression of esxG, esxH, infA, groES, rpmI, rpsA and lipF genes in a sensitive M. tuberculosis strain and in a multidrug-resistant clinical isolate. Here, we have evaluated the expression of these genes in 24 clinical isolates that belong to different lineages and have different drug resistance profiles. In vitro, growth kinetics analysis showed no difference in the growth of the clinical isolates, and thus drug resistance occurred without a fitness cost. However, a quantitative reverse transcription PCR analysis of gene expression revealed high variability among the clinical isolates, including those with similar drug resistance profiles. Due to the complexity of gene regulation pathways and the wide diversity of M. tuberculosis lineages, the use of gene expression as a molecular signature for drug resistance is not straightforward. Therefore, we recommend that the expression of M. tuberculosis genes be performed individually, and baseline expression levels should be verified among several different clinical isolates, before any further applications of these findings.
authors.affiliation: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, 64720, Nuevo León, México Universidad Autónoma de Nuevo León, UANL, Facultad de Ciencias Biológicas, San Nicolás de los Garza, 66451, Nuevo León, México.
authors.forename: Laura
authors.initials: L
authors.lastname: González-Escalante
authors.affiliation: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, 64720, Nuevo León, México.
authors.forename: Katia
authors.initials: K
authors.lastname: Peñuelas-Urquides
authors.affiliation: Universidad Autónoma de Nuevo León, UANL, Facultad de Medicina, Monterrey, 64460, Nuevo León, México.
authors.forename: Salvador
authors.initials: S
authors.lastname: Said-Fernández
authors.affiliation: Departamento de Inmunogenética, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, 64720, Nuevo León, México.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Silva-Ramírez
authors.affiliation: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, 64720, Nuevo León, México mario.bermudez@imss.gob.mx.
authors.forename: Mario
authors.initials: M
authors.lastname: Bermúdez de León
mesh_terms: D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015870:Gene Expression; D005798:Genes, Bacterial; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014376:Tuberculosis / Q000382:microbiology*
keywords: Mycobacterium tuberculosis; clinical isolates; drug resistance; first-line drugs; gene expression; tuberculosis