Redox-dependent condensation of the mycobacterial nucleoid by WhiB4

Chawla, Manbeena and Mishra, Saurabh and Anand, Kushi and Parikh, Pankti and Mehta, Mansi and Vij, Manika and Verma, Taru and Singh, Parul and Jakkala, Kishor and Verma, HN and AjitKumar, Parthasarathi and Ganguli, Munia and Seshasayee, Aswin Sai Narain and Singh, Amit (2018) Redox-dependent condensation of the mycobacterial nucleoid by WhiB4. In: REDOX BIOLOGY, 19 . pp. 116-133.

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Abstract

Oxidative stress response in bacteria is mediated through coordination between the regulators of oxidant-remediation systems (e.g. OxyR, SoxR) and nucleoid condensation (e.g. Dps, Fis). However, these genetic factors are either absent or rendered non-functional in the human pathogen Mycobacterium tuberculosis (Mtb). Therefore, how Mtb organizes genome architecture and regulates gene expression to counterbalance oxidative imbalance is unknown. Here, we report that an intracellular redox-sensor, WhiB4, dynamically links genome condensation and oxidative stress response in Mtb. Disruption of WhiB4 affects the expression of genes involved in maintaining redox homeostasis, central metabolism, and respiration under oxidative stress. Notably, disulfide-linked oligomerization of WhiB4 in response to oxidative stress activates the protein's ability to condense DNA. Further, overexpression of WhiB4 led to hypercondensation of nucleoids, redox imbalance and increased susceptibility to oxidative stress, whereas WhiB4 disruption reversed this effect. In accordance with the findings in vitro, ChIP-Seq data demonstrated non-specific binding of WhiB4 to GC-rich regions of the Mtb genome. Lastly, data indicate that WhiB4 deletion affected the expression of similar to 30% of genes preferentially bound by the protein, suggesting both direct and indirect effects on gene expression. We propose that WhiB4 structurally couples Mtb's response to oxidative stress with genome organization and transcription.

Item Type:	Journal Article
Publication:	REDOX BIOLOGY
Publisher:	ELSEVIER SCIENCE BV
Additional Information:	Copy right for this article belong to ELSEVIER SCIENCE BV
Keywords:	Fe-S cluster; Oxidative stress; Nucleoid associated protein; WhiB; Tuberculosis; Mycothiol
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	28 Nov 2018 15:13
Last Modified:	28 Nov 2018 15:13
URI:	http://eprints.iisc.ac.in/id/eprint/61188

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