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Regulation of Aggregatibacter (Actinobacillus) actinomycetemcomitans Leukotoxin Secretion by Iron

Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103,¹ Public Health Research Institute, International Center for Public Health, 225 Warren St., Newark, New Jersey 07103²

Received 9 August 2006/ Accepted 26 September 2006

The gram-negative oral and systemic pathogen Aggregatibacter (Actinobacillus) actinomycetemcomitans produces a leukotoxin (LtxA) that is a member of the RTX (repeats in toxin) family of secreted bacterial toxins. We have recently shown that LtxA has the ability to lyse erythrocytes, which results in a beta-hemolytic phenotype on Columbia blood agar. To determine if LtxA is regulated by iron, we examined beta-hemolysis under iron-rich and iron-limiting conditions. Beta-hemolysis was suppressed in the presence of FeCl₃. In contrast, strong beta-hemolysis occurred in the presence of the iron chelator deferoxamine. We found that secretion of LtxA was completely inhibited by free iron, but expression of ltxA was not regulated by iron. Free chromium, cobalt, and magnesium did not affect LtxA secretion. Other LtxA-associated genes were not regulated by iron. Thus, iron appears to play an important role in the regulation of LtxA secretion in A. actinomycetemcomitans in a manner independent of gene regulation.

Published ahead of print on 13 October 2006.

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