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BMC microbiology
05 25, 2020;20 (1): 132.

LipF increases rifampicin and streptomycin sensitivity in a Mycobacterium tuberculosis surrogate.

Ana Leticia Arriaga-Guerrero, Carlos E Hernández-Luna, Joyce Rigal-Leal, Rene J Robles-González, Laura Adiene González-Escalante, Beatriz Silva-Ramírez, Roberto Mercado-Hernández, Javier Vargas-Villarreal, Mario Bermúdez de León, Katia Peñuelas-Urquides
Author Information
  1. Ana Leticia Arriaga-Guerrero: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
  2. Carlos E Hernández-Luna: Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.
  3. Joyce Rigal-Leal: Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.
  4. Rene J Robles-González: Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.
  5. Laura Adiene González-Escalante: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
  6. Beatriz Silva-Ramírez: Departamento de Inmunogenética, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
  7. Roberto Mercado-Hernández: Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México.
  8. Javier Vargas-Villarreal: Departamento de Biología Celular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
  9. Mario Bermúdez de León: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México.
  10. Katia Peñuelas-Urquides: Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, Nuevo León, México. katia.penuelasu@imss.gob.mx. ORCID
PMID: 32450809 DOI: 10.1186/s12866-020-01802-x

Abstract

BACKGROUND: Mortality due to tuberculosis (TB) has increased due to the development of drug resistance, the mechanisms of which have not been fully elucidated. Our research group identified a low expression of lipF gene in Mycobacterium tuberculosis clinical isolates with drug resistance. The aim of this work was to evaluate the effect of lipase F (LipF) expression on mycobacterial drug resistance.
RESULTS: The effects of expressing lipF from Mycobacterium tuberculosis in Mycobacterium smegmatis on resistance to antituberculosis drugs were determined with resazurin microtiter assay plate and growth kinetics. Functionality of ectopic LipF was confirmed. LipF expression reduced the rifampicin (RIF) and streptomycin (STR) minimum inhibitory concentration (MIC) from 3.12 μg/mL to 1.6 μg/mL and 0.25 μg/mL to 0.06 μg/mL respectively, moreover a reduced M. smegmatis growth in presence of RIF and STR compared with that of a control strain without LipF expression (p < 0.05 and p < 0.01) was shown.
CONCLUSIONS: LipF expression was associated with increased RIF and STR sensitivity in mycobacteria. Reduced LipF expression may contribute to the development of RIF and STR resistance in Mycobacterium species. Our findings provide information pertinent to understanding mycobacterial drug resistance mechanisms.

Keywords

LipF, lipases Mycobacterium Rifampicin-resistance Streptomycin-resistance Tuberculosis

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Grants

  1. FIS/IMSS/PROT/G17-2/1734/Instituto Mexicano del Seguro Social

MeSH Term

Bacterial Proteins
Cloning, Molecular
Down-Regulation
Drug Resistance, Multiple, Bacterial
Gene Expression Regulation, Bacterial
Lipase
Microbial Sensitivity Tests
Mycobacterium smegmatis
Mycobacterium tuberculosis
Rifampin
Streptomycin

Chemicals

Bacterial Proteins
Lipase
Rifampin
Streptomycin
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 2

Word Cloud

Created with Highcharts 10.0.0LipFresistanceexpressionMycobacteriumtuberculosisdrugRIFSTRdueincreaseddevelopmentmechanismslipFmycobacterialsmegmatisgrowthreducedrifampicinstreptomycin0p < 0sensitivityBACKGROUND:MortalityTBfullyelucidatedresearchgroupidentifiedlowgeneclinicalisolatesaimworkevaluateeffectlipaseFRESULTS:effectsexpressingantituberculosisdrugsdeterminedresazurinmicrotiterassayplatekineticsFunctionalityectopicconfirmedminimuminhibitoryconcentrationMIC312 μg/mL16 μg/mL25 μg/mL06 μg/mLrespectivelymoreoverMpresencecomparedcontrolstrainwithout0501shownCONCLUSIONS:associatedmycobacteriaReducedmaycontributespeciesfindingsprovideinformationpertinentunderstandingincreasessurrogatelipasesRifampicin-resistanceStreptomycin-resistanceTuberculosis

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