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How bugs overcome host defenses

Apr. 11, 2019, 10:30 AM

by Leigh MacMillan

Bacterial pathogens must acquire nutrient metals from the host to survive and cause disease. To counter infection, hosts attempt to starve bacteria by hiding metals away in a process called “nutritional immunity.” Bacteria are wily foes though, and they change in order to survive metal starvation.

In a series of studies, Eric Skaar, PhD, and colleagues have characterized how A. baumannii — a leading cause of ventilator-associated pneumonia — responds to zinc starvation.

The researchers discovered that during zinc starvation, A. baumannii increases expression of the gene for a cell wall-modifying protein they named ZrlA. They show that bacteria missing the gene for ZrlA had leaky cell walls, and that these defects sensitized A. baumannii to antibiotics in vitro and in an animal model of pneumonia. They also discovered metabolic changes in A. baumannii in response to zinc starvation.

The studies, published in Cell Reports and Cell Chemical Biology, highlight the therapeutic potential of targeting proteins that respond to metal starvation, such as ZrlA, to treat bacterial infections.

This research was supported by grants from the National Institutes of Health (AI101171, GM118157, GM113172).

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