HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 25, 16842-16848, June 23, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/25/16842    most recent M602294200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hamano, Y. Articles by Takagi, H. Search for Related Content PubMed PubMed Citation Articles by Hamano, Y. Articles by Takagi, H. Social Bookmarking                      What's this?

A Novel Enzyme Conferring Streptothricin Resistance Alters the Toxicity of Streptothricin D from Broad-spectrum to Bacteria-specific^*

Yoshimitsu Hamano¹, Nobuyasu Matsuura, Miwa Kitamura, and Hiroshi Takagi²

From the Department of Bioscience, Fukui Prefectural University, Fukui 910-1195, Japan and the Department of Life Science, Okayama University of Science, Okayama 700-0005, Japan

Streptothricins (STs) produced by Streptomyces strains are broad-spectrum antibiotics. All STs consist of a carbamoylated D-gulosamine to which the -lysine homopolymer (1 to 7 residues) and the amide form of the unusual amino acid streptolidine (streptolidine lactam) are attached. Although many ST-resistance genes have been identified in bacteria, including clinically isolated pathogens and ST-producing Streptomyces strains, only one resistance mechanism has been identified to date. This mechanism involves the modification of the ST molecule by monoacetylation of the moiety of the -lysine(s). In this study, we successfully isolated a novel ST-resistance gene (sttH) from Streptomyces albulus, which is a known ST nonproducer. The in vitro analysis of SttH demonstrated that this enzyme catalyzes the hydrolysis of the amide bond of streptolidine lactam, thereby conferring ST resistance. Interestingly, the selective toxicity of ST-D possessing 3x -lysine moiety was altered from broad-spectrum to bacteria-specific by the hydrolysis of streptolidine lactam, although ST-F (1x -lysine) was detoxified by SttH in both prokaryotes and eukaryotes (yeasts). STs have not been clinically developed due to their toxicities; however, in this study, we showed that hydrolyzed ST-D (ST-D-acid) exhibits potent antibacterial activity even when its toxicity against eukaryotic cells is reduced by SttH. This suggests that ST-D-acid is a potential candidate for clinical development or for use as a new lead compound for drug discovery.

Received for publication, March 10, 2006 , and in revised form, April 24, 2006.

^* This work was supported in part by grants from the Chisso Corporation and the Program for Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN) (to H. T.). 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 nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AB248874 [GenBank] (the DNA sequence of the 2.9-kb Sau3AI fragment containing the sttH gene).

¹ To whom correspondence may be addressed: 4-1-1 Matsuoka-Kenjojima, Eiheiji-cho, Fukui 910-1195, Japan. Tel.: 81-776-61-6000; Fax: 81-776-61-6015; E-mail: hamano{at}fpu.ac.jp. ² To whom correspondence may be addressed. E-mail: hiro{at}fpu.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?