If you have an ACS member number, please enter it here so we can link this account to your membership. (optional)

ACS values your privacy. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. We use the information you provide to make your reading experience better, and we will never sell your data to third party members.


Biological Chemistry

Novel vaccines block iron scavenging by bacteria

Agents starve bacteria by raising antibodies to capture the small molecules the microbes release to harvest iron

by Stu Borman
November 9, 2016 | A version of this story appeared in Volume 94, Issue 45

Pie de foto: Un conjugado de un derivado del sideróforo enterobactina y de la proteína portadora de la subunidad B de la toxina del cólera producen anticuerpos que protegen la vida de ratones de la infección de la Salmonella.
Credit: Adaptado de Proc. Natl. Acad. Sci. USA
A conjugate of a derivative of the siderophore enterobactin and the carrier protein cholera toxin subunit B elicited antibodies that protected live mice from Salmonella infection.

Like Star Wars destroyers that send out pods on supply missions, some bacteria deploy small molecules called siderophores to collect the essential nutrient iron from hosts they infect. Two research groups now report a type of vaccine that programs animals’ immune systems to capture siderophores, killing invading bacteria by starving them of iron.

The strategy could become a new way to protect people from infections by Gram-negative bacteria, which use siderophores. Expanding the arsenal against these pathogens is an urgent necessity because many strains have become resistant to existing antibiotics. Antibiotic vaccines are already available for conditions such as meningitis, Haemophilus influenzae infections, pneumonia, and urinary tract infections, but some are toxic or only weakly protective, so scientists welcome new vaccine types.

Seven years ago, Raymond J. Bergeron and coworkers at the University of Florida induced mice to produce antibodies against a siderophore called vibriobactin used by Vibrio bacteria, which cause cholera (J. Med. Chem. 2009, DOI: 10.1021/jm900119q). However, they did not evaluate the ability of the antibodies to protect live animals from cholera because good animal models for Vibrio infection are not available.

Commenting on the new studies, Bergeron says the siderophore-based vaccine concept “still has a ways to go.” For example, some bacteria use multiple siderophores, so blocking just one may not work for all bacteria. Nevertheless, the new studies “are like absolution to us,” he says. “Coupled with what we did earlier, they show that this is a credible approach.”

Siderophores collect iron from bacterial hosts and then bring it back home by recognizing specialized receptors on bacterial cell membranes. To disrupt this process, Elizabeth M. Nolan of Massachusetts Institute of Technology, Manuela Raffatellu of the University of California, Irvine, and coworkers designed and synthesized derivatives of a Salmonella siderophore and conjugated it to a carrier protein that would induce an immune response in mice. Animals immunized with the conjugates developed antibodies that recognize and sequester the siderophores, killing Salmonella in the gut of infected mice (Proc. Natl. Acad. Sci.USA 2016, DOI: 10.1073/pnas.1606290113).

Harry L. T. Mobley’s group at the University of Michigan Medical School and coworkers immunized mice with two types of Escherichia coli siderophores conjugated to an immunogenic carrier protein. These siderophore-protein conjugates protected mice against urinary tract infections (Proc. Natl. Acad. Sci.USA 2016, DOI: 10.1073/pnas.1606324113). In fact, the siderophores were immunogenic enough on their own to elicit an immune response even when they were not protein-conjugated.

Bergeron says siderophore vaccines haven’t been taken seriously enough by research funding agencies. “People will pay attention now,” he says. “I hope the concept goes forward and does something for patients.”

This article has been translated into Spanish by and can be found here.



This article has been sent to the following recipient:

Chemistry matters. Join us to get the news you need.