Insight about cell wall remodulation triggered by rifampicin in Mycobacterium tuberculosis

Jean Eduardo Meneguello; Gláucia Sayuri Arita; João Vitor de Oliveira Silva; Luciana Dias Ghiraldi-Lopes; Katiany Rizzieri Caleffi-Ferracioli; Vera Lucia Dias Siqueira; Regiane Bertin de Lima Scodro; Eduardo Jorge Pilau; Paula Aline Zannetti Campanerut-Sá; Rosilene Fressatti Cardoso

doi:10.1016/j.tube.2020.101903

Insight about cell wall remodulation triggered by rifampicin in Mycobacterium tuberculosis

Tuberculosis (Edinb). 2020 Jan:120:101903. doi: 10.1016/j.tube.2020.101903. Epub 2020 Jan 13.

Affiliations

¹ Postgraduate Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, PR, Brazil.
² Postgraduate Program in Health Sciences, Center of Health Sciences, State University of Maringá, Maringá, PR, Brazil.
³ Postgraduate Program in Chemistry, Department of Chemistry, State University of Maringá, Maringá, PR, Brazil.
⁴ Postgraduate Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, PR, Brazil; Postgraduate Program in Health Sciences, Center of Health Sciences, State University of Maringá, Maringá, PR, Brazil. Electronic address: paulacampanerut@gmail.com.
⁵ Postgraduate Program in Biosciences and Physiopathology, Department of Clinical Analysis and Biomedicine, State University of Maringá, Maringá, PR, Brazil; Postgraduate Program in Health Sciences, Center of Health Sciences, State University of Maringá, Maringá, PR, Brazil.

PMID: 32090864
DOI: 10.1016/j.tube.2020.101903

Abstract

Rifampicin plays an important role during the treatment of tuberculosis, which makes it to be recommended throughout the regimen. The molecular target for rifampicin activity and resistance is the bacterial RNA polymerase coded by rpoB. However, it has been observed that Mycobacterium tuberculosis could use different metabolic pathways contributing to drug activity/resistance. In this sense, Proteomics analysis has been a key aspect towards the understanding of the dynamic genome expression triggered by drugs and other M. tuberculosis hostile stimuli. Herein, we aimed to report the changes in the M. tuberculosis protein profile triggered by rifampicin. The M. tuberculosis H₃₇Rv strain was submitted to 12, 24 and 48 h of rifampicin challenge, at the minimal inhibitory concentration (0.03 μg mL^-1), and proteins were extracted. The protein identification was carried out by liquid chromatography coupled to mass spectrometry (LC-MS). Four proteins, Ino1 (Rv0046c), FabD (Rv2243), EsxK (Rv1197) and PPE60 (Rv3478) were statistically underexpressed over 48 h of rifampicin exposure, indicating that in addition to the known activity of rifampin in transcriptional machinery in M. tuberculosis, processes related to disturbance in cell wall synthesis and lipid metabolism in the bacillus are also triggered by rifampicin contributing to bacillus death.

Keywords: Drug resistance; Mass spectrometry; Mycobacterium tuberculosis; Proteomics; Rifampicin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibiotics, Antitubercular / pharmacology*
Bacterial Proteins / metabolism*
Cell Wall / drug effects*
Cell Wall / metabolism
Chromatography, High Pressure Liquid
Microbial Sensitivity Tests
Mycobacterium tuberculosis / drug effects*
Mycobacterium tuberculosis / metabolism
Protein Interaction Maps
Proteomics
Rifampin / pharmacology*
Tandem Mass Spectrometry
Time Factors

Substances

Antibiotics, Antitubercular
Bacterial Proteins
Rifampin