NapA (Rv0430), a Novel Nucleoid-Associated Protein that Regulates a Virulence Operon in Mycobacterium tuberculosis in a Supercoiling-Dependent Manner

Datta, Chandreyee and Jha, Rajiv Kumar and Ganguly, Sohini and Nagaraja, Valakunja (2019) NapA (Rv0430), a Novel Nucleoid-Associated Protein that Regulates a Virulence Operon in Mycobacterium tuberculosis in a Supercoiling-Dependent Manner. In: JOURNAL OF MOLECULAR BIOLOGY, 431 (8). pp. 1576-1591.

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Abstract

Comparison of Mycobacterium tuberculosis with Escherichia coli reveals a reduction in the diversity of DNA-managing proteins, such as DNA topoisomerases, although genome sizes are similar for the two species. The same is true for nucleoid-associated proteins (NAPs), important factors in bacterial chromosome compaction, chromosome remodeling, and regulation of gene expression. In a search for still uncharacterized NAPs, we found that M. tuberculosis protein Rv0430 has NAP-like features: it binds to DNA in a length-and supercoil-dependent fashion, prefers AfT-rich DNA sequences, protects DNA from damaging agents, and modulates DNA supercoiling. At a ratio of 1 dimer/40 bps of DNA, Rv0430 bridges distant DNA segments; at 1 dimer/20 bps, it coats DNA, forming inflexible rods. Rv0430 also stimulates the DNA relaxation activity of topoisomerase I. Remarkably, Rv0430 stimulates its own promoter in a supercoil-dependent manner. It is the first gene of an operon harboring two regulators of M. tuberculosis virulence (virR and sodC), and controls the expression of these downstream virulence regulators and therefore itself is a virulence regulator. The sensitivity of rv0430 expression to supercoiling is consistent with supercoiling being important for infection by M. tuberculosis. Thus, Rv0430 is a novel NAP, doubling up as a topology modulator of M. tuberculosis. (C) 2019 Elsevier Ltd. All rights reserved.

Item Type:	Journal Article
Publication:	JOURNAL OF MOLECULAR BIOLOGY
Publisher:	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Additional Information:	Copyright of this aricle belongs to JOURNAL OF MOLECULAR BIOLOGY
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	29 May 2019 06:45
Last Modified:	29 May 2019 06:45
URI:	http://eprints.iisc.ac.in/id/eprint/62629

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