Examining how robustness and paralysis to the same stress manifests in iron-starved bacteria

Bacteria are ubiquitous with wide-ranging impacts on human health, agriculture, biotechnology, and the environment. In many circumstances, bacteria exist in non-ideal conditions where they cope with stresses to survive and grow. With a single stress, bacteria can commit their resources to counter that sole threat, and most knowledge of bacterial stress responses comes from single stress conditions.

However, stresses are rarely isolated, and when more than one stress is present, how resources are distributed to cope with simultaneous challenges remains largely an open question. This is especially true when one of the stresses is starvation for an essential nutrient, such as iron, which is involved in many biological processes. The goal of this project is to increase understanding of how iron-starved bacteria, which are prevalent in diverse environments (e.g., inside immune cells and soil), cope with additional stresses.

The additional stress to be investigated is nitric oxide, which is a toxic metabolite produced by immune cells and soil bacteria that can co-occur with iron starvation. This project is poised to positively impact human health and agriculture, as well as increase public awareness of and participation in biosciences and bioengineering through working with high school, community college, undergraduate, and graduate students.

This project investigates how Fe-starved Escherichia coli defend themselves against nitric oxide and examines why Fe-starved Pseudomonas aeruginosa cannot do the same. Notably, these bacterial species comprise opposite extremes of adaptability in this multi-stress condition (robustness and paralysis), which provides the opportunity to reveal principles of adaptation for Fe-starved bacteria.

The scientific questions to be addressed include: (i) How is Fe provided for stress responses in Fe-starved bacteria? (ii) How do Fe-strapped metabolisms, which restrict production of reducing power, supply enough reducing power for new stress responses? (iii) What distinguishes organisms that can adapt to new stresses when Fe-starved (e.g., E. coli) from those that cannot (e.g., P. aeruginosa)? These questions focus on resource recycling and regulation in Fe-starved bacteria and to answer them genetic mutants, tools from synthetic biology, mass spectrometry, and systems-level modeling are used.

Results from this project will elucidate principles of adaptation for Fe-starved bacteria that are likely to be applicable to microbes constrained for resources in other ways. Such constraints are usually due to the universal importance of recycling and regulation to the survival of starved bacteria.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.