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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #247740
Title: Transcriptional response of Leptospira interrogans to iron limitation and characterization of a PerR homolog

Author
item LO, MIRANDA
item MURRAY, GERALD
item KHOO, CHEN
item HAAKE, DAVID
item Zuerner, Richard
item ADLER, BEN

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/17/2010
Publication Date: 11/1/2010
Citation: Lo, M., Murray, G., Khoo, C.A., Haake, D., Zuerner, R.L., Adler, B. 2010. Transcriptional response of Leptospira interrogans to iron limitation and characterization of a PerR homolog. Infection and Immunity. 78(11):4850-4859.

Interpretive Summary: Leptospira interrogans is the causative agent of leptospirosis, a zoonosis of global significance. Iron is essential for growth of most bacterial species. Since availability of iron is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. In this paper, we describe studies that characterize the response of Leptospira to iron limitation and examine how a novel mutation in a putative fur gene affects gene expression. Our results provide insights into the role of iron in leptospiral metabolism and genes, which may be important for in vivo survival and virulance.

Technical Abstract: Leptospira interrogans is the causative agent of leptospirosis, a zoonosis of global significance. Iron is essential for growth of most bacterial species. Since availability of iron is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur. L. interrogans has four predicted Fur homologues and we have constructed a transposon mutant in one of these, LA185. Microarray analysis showed that 43 genes were up-regulated and 50 genes were down-regulated under iron-limiting conditions. Genes encoding proteins predicted to be involved in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were over-represented in the up-regulated list, while 54% of differentially expressed genes had no known function. We also identified 16 up-regulated genes of unknown function, which are absent from the saprophytic L. biflexa, and therefore, may encode potential virulence factors. Microarrays were also used to compare parent and mutant strains to investigate the function of LA1857. Results showed that LA1857 is not involved in the regulation of many genes which were iron-responsive, indicating that LA1857 is not a global regulator of iron homeostasis. However, the up-regulation of heme biosynthetic genes and a putative catalase in the mutant suggests that LA1857 may play a role in responses to metal limitation and oxidative stress. Our results provide insights into the role of iron in leptospiral metabolism and genes, which may be important for in vivo survival and virulence.