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J. Biol. Chem., Vol. 280, Issue 4, 2636-2643, January 28, 2005

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New Genes Implicated in the Protection of Anaerobically Grown Escherichia coli against Nitric Oxide^*

Marta C. Justino, João B. Vicente, Miguel Teixeira, and Lígia M. Saraiva¶

From the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Apartado 127, Avenida da República (EAN), 2781-901 Oeiras, Portugal

Nitric oxide produced by activated macrophages plays a key role as one of the immune system's weapons against pathogens. Because the lifetime of nitric oxide is short in aerobic conditions, whereas in anaerobic conditions the cytotoxic effects of nitric oxide are greatly increased as in the infection/inflammation processes, it is important to establish which systems are able to detoxify nitric oxide under anaerobic conditions. In the present work a new set of Escherichia coli K-12 genes conferring anaerobic resistance to nitric oxide is presented, namely the gene product of YtfE and a potential transcriptional regulator of the helix-turn-helix LysR-type (YidZ). The crucial role of flavohemoglobin for anaerobic nitric oxide protection is also demonstrated. Furthermore, nitric oxide is shown to cause a significant alteration of the global E. coli gene transcription profile that includes the increase of the transcript level of genes encoding for detoxification enzymes, iron-sulfur cluster assembly systems, DNA-repairing enzymes, and stress response regulators.

Received for publication, September 27, 2004 , and in revised form, November 10, 2004.

^* This work was supported in part by Fundação para a Ciência e a Tecnologia Project Grants POCTI/1999/BME/36558 and POCTI/2002/BME/44597 (to M. T. and L. M. S). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental table 1 ("Genes induced by NO treatment") and supplemental table 2 ("Genes repressed by NO treatment").

Recipient of Fundação para a Ciência e a Tecnologia Grant SFRH/BD/13756/2003.

Recipient of Fundação para a Ciência e a Tecnologia Grant SFRH/BD/9136/2002.

^¶ To whom correspondence should be addressed. Tel.: 351-214469328; Fax: 351-214411277; E-mail: lst{at}itqb.unl.pt.

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