Comparing mRNA expression and protein abundance in MDR Mycobacterium tuberculosis: Novel protein candidates, Rv0443, Rv0379 and Rv0147 as TB potential diagnostic or therapeutic targets

Tasbiti, Alireza Hadizadeh; Yari, Shamsi; Siadat, Seyed Davar; Karimipoor, Morteza; Badmasti, Farzad; Masoumi, Maryam; Abdolrahimi, Farid; Khanipour, Sharareh; Hassanzadeh, Seyed Mehdi; Nobar, Mostafa Ghalami; Yari, Fatemeh

doi:10.1016/j.btre.2021.e00641

Cited by 2 publications

(1 citation statement)

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“…Given the various properties of HupB and/or its homolog Hlp (Prabhakar et al, 1998 ; Katsube et al, 2007 ; Kumar et al, 2010 ; Bhowmick et al, 2014 ; Gupta et al, 2014 ; Pandey et al, 2014a ; Ghosh et al, 2016 ; Hołówka et al, 2017 ; Kalra et al, 2018 ; Yaseen et al, 2018 ; Datta et al, 2019 ), its expression per se being modulated under low iron conditions (Pandey et al, 2014b ), non-replicating persistence (Lee et al, 1998 ; Shires and Steyn, 2001 ; Betts et al, 2002 ; Anuchin et al, 2010 ), and upon exposure of Mtb to INH (Reddy et al, 2009 ; Whiteford et al, 2011 ; Hadizadeh Tasbiti et al, 2016 ; Sakatos et al, 2018 ; Arora et al, 2021 ; Hadizadeh Tasbiti et al, 2021 ), we hypothesized that to survive and respond to different host- and antibiotic-mediated stresses, Mtb employs HupB as a key player.…”

Section: Resultsmentioning

confidence: 99%

HupB, a nucleoid-associated protein, is critical for survival of Mycobacterium tuberculosis under host-mediated stresses and for enhanced tolerance to key first-line antibiotics

et al. 2022

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To survive and establish its niche, Mycobacterium tuberculosis (Mtb) engages in a steady battle against an array of host defenses and a barrage of antibiotics. Here, we demonstrate that Mtb employs HupB, a nucleoid-associated protein (NAP) as its key player to simultaneously battle and survive in these two stress-inducing fronts. Typically, NAPs are key to bacterial survival under a wide array of environmental or host-mediated stresses. Here, we report that for Mtb to survive under different macrophage-induced assaults including acidic pH, nutrient depletion, oxidative and nitrosative stresses, HupB presence is critical. As expected, the hupB knockout mutant is highly sensitive to these host-mediated stresses. Furthermore, Mtb aptly modulates HupB protein levels to overcome these stresses. We also report that HupB aids Mtb to gain tolerance to high levels of rifampicin (RIF) and isoniazid (INH) exposure. Loss of hupB makes Mtb highly susceptible to even short exposures to reduced amounts of RIF and INH. Overexpressing hupB in Mtb or complementing hupB in the hupB knockout mutant triggers enhanced survival of Mtb under these stresses. We also find that upon loss of hupB, Mtb significantly enhances the permeability of its cell wall by modulating the levels of several surface lipids including phthiocerol dimycocerosates (PDIMs), thus possibly influencing overall susceptibility to host-mediated stresses. Loss of hupB also downregulates efflux pump expression possibly influencing increased susceptibility to INH and RIF. Finally, we find that therapeutic targeting of HupB with SD1, a known small molecule inhibitor, significantly enhances Mtb susceptibility to INH and THP-1 macrophages and significantly reduces MIC to INH. Thus, our data strongly indicate that HupB is a highly promising therapeutic target especially for potential combinatorial shortened therapy with reduced INH and RIF doses.

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Section: Resultsmentioning

confidence: 99%

HupB, a nucleoid-associated protein, is critical for survival of Mycobacterium tuberculosis under host-mediated stresses and for enhanced tolerance to key first-line antibiotics

et al. 2022

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Proteomics in Biomarker Discovery for Tuberculosis: Current Status and Future Perspectives

et al. 2022

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Tuberculosis (TB) continues to threaten many peoples’ health worldwide, regardless of their country of residence or age. The current diagnosis of TB still uses mainly traditional, time-consuming, and/or culture-based techniques. Efforts have focused on discovering new biomarkers with higher efficiency and accuracy for TB diagnosis. Proteomics—the systematic study of protein diversity—is being applied to the discovery of novel protein biomarkers for different types of diseases. Mass spectrometry (MS) technology plays a revolutionary role in proteomics, and its applicability benefits from the development of other technologies, such as matrix-based and immune-based methods. MS and derivative strategies continuously contribute to disease-related discoveries, and some promising proteomic biomarkers for efficient TB diagnosis have been identified, but challenges still exist. For example, there are discrepancies in the biomarkers identified among different reports and the diagnostic accuracy of clinically applied proteomic biomarkers. The present review summarizes the current status and future perspectives of proteomics in the field of TB biomarker discovery and aims to elicit more promising findings for rapid and accurate TB diagnosis.

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Comparing mRNA expression and protein abundance in MDR Mycobacterium tuberculosis: Novel protein candidates, Rv0443, Rv0379 and Rv0147 as TB potential diagnostic or therapeutic targets

Cited by 2 publications

References 53 publications

HupB, a nucleoid-associated protein, is critical for survival of Mycobacterium tuberculosis under host-mediated stresses and for enhanced tolerance to key first-line antibiotics

HupB, a nucleoid-associated protein, is critical for survival of Mycobacterium tuberculosis under host-mediated stresses and for enhanced tolerance to key first-line antibiotics

Proteomics in Biomarker Discovery for Tuberculosis: Current Status and Future Perspectives

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