An ion for an iron: streptococcal metal homeostasis under oxidative stress

The Biochemical Journal
Nicholas S Jakubovics

Abstract

The ability of opportunistic pathogens such as Group A Streptococcus (GAS) to transition between mucosal colonisation and invasive disease requires complex systems for adapting to markedly different host environments. The battle to acquire essential trace metals such as manganese and iron from the host is central to pathogenesis. Using a molecular genetic approach, Turner et al. [Biochem. J. (2019) 476, 595-611] show that it is not just individual metal concentrations that are important, but the ratio of iron to manganese within cells. Increasing this ratio by knocking out pmtA, encoding the Fe(II) exporter PmtA, or by disrupting mtsA, encoding an MtsABC Mn(II)-import system component, led to reductions in superoxide dismutase (SodA) activity and increased sensitivity to oxidative stress. The authors show that SodA is at least 4-fold more active with Mn bound than with Fe and speculate that high intracellular Fe:Mn ratios reduce superoxide dismutase activity through the mismetalation of SodA. Challenging wild-type GAS with 1 mM H2O2 led to a decrease in Fe:Mn ratio and a 3-fold increase in SodA activity, indicating that modulation of the balance between intracellular Fe and Mn may play an important role in adaptation to oxidati...Continue Reading

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