M. tuberculosis ferritin (Rv3841): Potential involvement in Amikacin (AK) & Kanamycin (KM) resistance

Cytosolic Proteome Profiling of Aminoglycosides Resistant Mycobacterium tuberculosis Clinical Isolates Using MALDI-TOF/MS

“…2DE/MS has an advantage over the traditional methods (SDS-PAGE, chromatography and sequencing) as not only the identification of a large number of unknown proteins but also protein species separation. Several reports (whole cell lysates and membrane and membrane associated proteins) on aminoglycosides drug resistance and identification of diagnostics/drug targets employing proteomic and bioinformatic approaches exists (Sharma et al, 2010a, 2014, 2015a,b, 2016; de Souza et al, 2011; Kumar et al, 2013) which suggested that over expressed hypothetical proteins (Rv3867, Rv3224, Rv0148, Rv2744c), universal stress protein (Rv2005c) and some known proteins (involved in various pathways) might be involved in aminoglycosides resistance. However, to the best of our knowledge, no study on cytosolic proteome analysis with AK and KM resistant M. tuberculosis isolates has been reported.…”

“…Comparative proteomic studies addressing whole cell lysate and membrane and membrane associated proteins of aminoglycosides resistance isolates have been reported (Kumar et al, 2013; Sharma et al, 2015b). Recently we have reported involvement of ferritin (a cytoplasmic protein) in AK and KM resistance (Sharma et al, 2016). However, purely cytosolic expression proteome of aminoglycosides resistant M. tuberculosis isolates have not been explored.…”

M. tuberculosis Hypothetical Proteins and Proteins of Unknown Function: Hope for Exploring Novel Resistance Mechanisms as well as Future Target of Drug Resistance

“…Through in silico /bioinformatic (Interproscan and molecular docking) analysis they showed that drugs binds to the conserved domains of hypothetical proteins/uncharacterized proteins and suggested that the over expression of a panel of uncharacterized and hypothetical proteins might neutralize/compensate the effect of drugs. Sharma et al (2015b, 2016a) reported that inducible over expression of cloned known and unknown proteins (Rv0148 and Rv3841) in E. coli makes it two- to threefolds more resistant under drug pressure. Here we emphasize that detailed bioinformatics analysis (like protein-protein interaction) of these uncharacterized and hypothetical proteins might predict their interactive partners (other proteins) which are involved in various pathways of M. tuberculosis system biology (exploring/deciphering the M. tuberculosis network biology through in silico /holistic approaches) and might give a clue for novel mechanism of drug resistance or future target.…”

“…Pup-proteasome system controlled by pupylation contributes to the virulence/survival strategy of M. tuberculosis in the host and makes the bacteria more resistant to various stresses. STRING-10 (Proteins-proteins interaction) predicted the potential interactive partners and suggested the metabolic pathways involved in resistance (Sharma et al, 2016a,b). Rv0148 (hypothetical protein/putative short-chain type dehydrogenase/reductase) was overexpressed in aminoglycosides resistant M. tuberculosis and had conserved SDR domain.…”

Role of Bacterioferritin & Ferritin in M. tuberculosis Pathogenesis and Drug Resistance: A Future Perspective by Interactomic Approach

“…Two dimensional gel electrophoresis coupled with mass spectrometry is the best accepted approach for expression proteomics (Lata et al, 2015a,b; Sharma et al, 2015b, 2016b; Sharma and Bisht, 2016). Since last decade a panel of proteomics and bioinformatics studies related to aminoglycosides resistance have been accumulated (Sharma et al, 2010, 2014, 2015b,a, 2016a,b; Kumar et al, 2013; Sharma and Bisht, 2017a,b). Here we emphasized on the M. tuberculosis iron storage proteins (bacterioferritin and ferritin) and their interactive protein partners which might be involved in pathogenesis, virulence and drug resistance.…”