Iron acquisition and utilization by Rhodococcus equi: potential virulence factors

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to digital@library.tamu.edu, referencing the URI of the item.Includes bibliographical references (leaves 43-54).Issued also on microfiche from Lange Micrographics.The course of any infection depends upon the pathogenicity of a particular organism and the status of the host's defense mechanisms. Because most bacterial pathogens need iron to multiply, they must develop mechanisms to acquire iron in the severely iron-restricted environment in vivo. A highly effective iron acquisition system is therefore essential for virulence of pathogenic bacteria. The importance of- and mechanisms for- obtaining iron from the environment have been described for many bacteria; however, they have not been determined for Rhodococcus equi. R. equi is a facultative intracellular pathogen that causes severe pyogranulomatous pneumonia in foals and immunocompromised humans. In vitro growth of virulent and avirulent R. equi was significantly decreased in response to severe iron limitation caused by the iron chelator 2,2'-dipyridyl. This response was abolished by the addition of excess iron. When grown in the presence of deferoxamine mesylate, another iron chelator, R. equi growth was not inhibited, suggesting that R. equi was able to utilize the deferoxamine-bound-iron. The addition of excess iron to the growth media did not alter bacterial growth. Growth of R. equi in iron deficient media, containing 2,2'-dipyridyl, was significantly increased in the presence of holotransferrin, whereas growth was inhibited in the presence of apotransferrin and lactoferrin, thereby suggesting that R. equi can utilize transferrin-bound iron. A 22- to 24- kDa iron-regulated virulence-associated highly immunogenic cell wall protein was identified. Only virulent R. equi produced the protein, but it was significantly up-regulated under iron-limiting conditions, and serum from foals naturally infected with R. equi reacted strongly by immunoblot to this protein. These findings suggest that the 85- to 90- kb virulence-associated R. equi plasmid encodes for a 22-to 24- kDa iron-regulated protein during infection. The mechanisms by which virulent R. equi obtain and utilize iron may represent important virulence factors