The ΔCysK2 mutant of Mycobacterium tuberculosis is sensitive to vancomycin associated with changes in cell wall phospholipid profile

Carine Sao Emani; Adrian Richter; Albel Singh; Apoorva Bhatt; Yossef Av-Gay

doi:10.1016/j.bbrc.2022.07.096

The ΔCysK₂ mutant of Mycobacterium tuberculosis is sensitive to vancomycin associated with changes in cell wall phospholipid profile

Carine Sao Emani^*, Adrian Richter, Albel Singh, Apoorva Bhatt, Yossef Av-Gay^*

^*Corresponding author for this work

Biosciences

Research output: Contribution to journal › Article › peer-review

Abstract

Cysteine plays a versatile role in cellular physiology and has previously been shown to be instrumental to Mycobacterium tuberculosis (M.tb) pathophysiology. In this study, we have generated mutants deficient in CysK₂ and CysH, the key Cysteine, biosynthetic enzymes. In contrast to the ΔcysH mutant, the ΔcysK₂ mutant is not an auxotroph and as such not essential for cysteine biosynthesis. Interestingly, the ΔcysK₂ mutant shows increased sensitivity to cumene hydroperoxide, vitamin C, diamide, rifampicin and Vancomycin and shows alterations in phospholipid profile of Mtb cell wall. Our findings suggest that alteration in phospholipids content of M.tb cell wall by CysK₂ may form a mode of defence against selected antibiotics and oxidative stress.

Original language	English
Pages (from-to)	120-126
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	624
Early online date	2 Aug 2022
DOIs	https://doi.org/10.1016/j.bbrc.2022.07.096
Publication status	Published - 8 Oct 2022

Bibliographical note

Keywords

Cell Wall
Cysteine/genetics
Mycobacterium tuberculosis/genetics
Phospholipids
Vancomycin/pharmacology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2022.07.096Licence: None: All rights reserved

Cite this

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title = "The ΔCysK2 mutant of Mycobacterium tuberculosis is sensitive to vancomycin associated with changes in cell wall phospholipid profile",

abstract = "Cysteine plays a versatile role in cellular physiology and has previously been shown to be instrumental to Mycobacterium tuberculosis (M.tb) pathophysiology. In this study, we have generated mutants deficient in CysK2 and CysH, the key Cysteine, biosynthetic enzymes. In contrast to the ΔcysH mutant, the ΔcysK2 mutant is not an auxotroph and as such not essential for cysteine biosynthesis. Interestingly, the ΔcysK2 mutant shows increased sensitivity to cumene hydroperoxide, vitamin C, diamide, rifampicin and Vancomycin and shows alterations in phospholipid profile of Mtb cell wall. Our findings suggest that alteration in phospholipids content of M.tb cell wall by CysK2 may form a mode of defence against selected antibiotics and oxidative stress.",

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AU - Sao Emani, Carine

AU - Richter, Adrian

AU - Singh, Albel

AU - Bhatt, Apoorva

AU - Av-Gay, Yossef

PY - 2022/10/8

Y1 - 2022/10/8

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AB - Cysteine plays a versatile role in cellular physiology and has previously been shown to be instrumental to Mycobacterium tuberculosis (M.tb) pathophysiology. In this study, we have generated mutants deficient in CysK2 and CysH, the key Cysteine, biosynthetic enzymes. In contrast to the ΔcysH mutant, the ΔcysK2 mutant is not an auxotroph and as such not essential for cysteine biosynthesis. Interestingly, the ΔcysK2 mutant shows increased sensitivity to cumene hydroperoxide, vitamin C, diamide, rifampicin and Vancomycin and shows alterations in phospholipid profile of Mtb cell wall. Our findings suggest that alteration in phospholipids content of M.tb cell wall by CysK2 may form a mode of defence against selected antibiotics and oxidative stress.

KW - Cell Wall

KW - Cysteine/genetics

KW - Mycobacterium tuberculosis/genetics

KW - Phospholipids

KW - Vancomycin/pharmacology

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DO - 10.1016/j.bbrc.2022.07.096

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