Biotechnology

Researchers at University of Sheffield release new data on gene therapy

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"Here we show that expression of hmp is greatly enhanced by NO but not by other haem ligands (azide, cyanide and carbon monoxide). Flavohaemoglobins of other pathogenic bacteria have been implicated in conferring resistance to NO in vitro and in macrophage-like cells but the role of the E. coli flavohaemoglobin has not been studied in macrophages. We therefore compared survival of wild-type K-12 E. coli cells and an isogenic hmp mutant after internalisation by human macrophages. Wild-type bacteria survived significantly better than the hmp mutant after incubation with macrophages, despite binding and internalisation rates being similar for both strains. Unexpectedly, however, when grown in MOPS minimal medium, in mixed cultures, more hmp mutant cells were recovered than wild-type. Significantly, an hmp mutant failed to exhibit swarming motility on soft agar and this phenotype was rescued by a plasmid-borne copy of the wild-type hmp(+) gene. Thus, although Hmp constitutes an important mechanism of protection from NO-mediated killing by human macrophages in the model E. coli strain K-12, and probably contributes to the survival of enteropathogenic E. coli during the intestinal inflammatory response, synthesis of Hmp in vitro may represent a selective disadvantage," wrote T.M. Stevanin and colleagues, University of Sheffield.

The researchers concluded: "The lack of swarming motility of the hmp mutant and its aflagellate state suggest that Hmp synthesis is a metabolic burden in the absence of NO-related stresses."

Stevanin and colleagues published their study in Gene (The hmp gene encoding the NO-inducible flavohaemoglobin in Escherichia coli confers a protective advantage in but not in vitro: Links resisting killing within macrophages, with swarming motility. Gene, 2007;398(1-2 Sp. Is):62-68).

For additional information, contact R.K. Poole, University of Sheffield, Dept. of Molecular Biology & Biotechnology, 5th Court, Sheffield S10 2TN, S Yorkshire, UK.

The publisher's contact information for the journal Gene is: Elsevier Science BV, PO Box 211, 1000 AE Amsterdam, Netherlands.

Keywords: United Kingdom, Sheffield, Biotechnology, Gene Therapy, University of Sheffield.

This article was prepared by Genetics & Environmental Business Week editors from staff and other reports. Copyright 2007, Genetics & Environmental Business Week via NewsRx.com.