1887

Abstract

A limited understanding of iron uptake mechanisms is available for , a haemolytic human pathogen capable of using a variety of haemoproteins in addition to ferric and ferrous iron. This study characterizes a transporter named (for treptococcal ron ptake), which consists of an ATP-binding protein (SiuA), a substrate-binding protein (SiuD), and two membrane permease subunits (SiuBG). An mutant was constructed and characterized. The mutant demonstrated growth reduction in comparison to the parent strain when grown in complex medium containing iron in the form of blood, haemoglobin or serum. Only a small reduction in the growth of the mutant was observed in medium containing ferric iron. However, in iron uptake assays the mutant showed a decrease of approximately 30 % in Fe incorporation. Addition of 6 μM haem to the medium inhibited Fe uptake by the wild-type by 76 %, while addition of protoporphyrin IX did not, suggesting that utilization of haem as an iron source is responsible for the inhibition of Fe uptake. Inactivation of moderately reduced the ability of haem to inhibit Fe incorporation by the cells. Inactivation of (encoding a membrane permease of a second iron transporter) had a similar outcome, and inactivation of both transporters had a cumulative effect. These observations implicate both the and transporters in haem utilization by . Studies in a zebrafish infection model revealed that the mutant was attenuated in both intramuscular and intraperitoneal routes of infection. Together these observations show that the system is an iron acquisition pathway in that is important both and .

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2005-11-01
2019-11-15
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