Metal utilization in genome-reduced bacteria: Do human mycoplasmas rely on iron?

Abstract

Graphical abstract

Iron(III) Binding Properties of PF1140, a Fungal N-Hydroxypyridone, and Activity against Mycoplasma genitalium

“…Furthermore, M. genitalium grows in iron-deficient defined media and lacks iron acquisition and storage systems, suggesting it may not utilize iron at all. 15,32 Together, these results indicate that iron sequestration is not the mechanism by which PF1140 inhibits M. genitalium growth.…”

“…Further fueling our interest in natural product 1 was the recent data suggesting that metal utilization in M. genitalium is atypical in that it does not require iron; the Fur regulator responds to zinc availability instead of iron with Fur regulating nickel acquisition. 31 Therefore, the metal chelating ability of PF1140 may restrict the availability of essential metal ions and inhibit growth.…”

“…38 These sources of hydrogen peroxide may enhance PF1140 activity against M. genitalium in vivo. As M. genitalium lacks the systems to safely sequester intracellular iron (e.g., iron sulfur clusters and ferritin), 15 it may be more susceptible to PF1140 than organisms that have these systems. Future experiments should define the mechanism of PF1140 toxicity and determine whether M. genitalium low passage clinical isolates are similarly susceptible to this compound.…”

“…might similarly lack the requirement for iron and instead rely on other metals such as manganese and nickel for essential cell functions. 15 T h i s c o n t e n t i s Given the prominent role that iron plays in the life of most bacteria, 16 it is not surprising that pathways involved in metal acquisition, storage, and homeostasis have been the subjects of numerous attempts to control microbial pathogens. 17 Taking this idea in an intriguing direction, it has been proposed that metals could be effectively employed against bacteria in the form of metalloantibiotics.…”

“…In addition, recent evidence suggests that M. genitalium and some other Mycoplasma spp. might similarly lack the requirement for iron and instead rely on other metals such as manganese and nickel for essential cell functions …”