Fighting bacterial resistance

ARC Future Fellow, Dr Begoña Heras, specialises in investigating the molecular mechanisms underlying Gram-negative bacterial infections.

About 700,000 people around the world die annually from antimicrobial resistant (AMR) infections and, if no action is taken, it is estimated that such infections will kill ten million people a year by 2050.

Public health threat

“Antibiotics were wonder drugs when they were discovered. They transformed the course of modern medicine and our quality of life,” said Dr Begoña Heras, ARC Future Fellow. “However, in the last few decades bacterial resistance has increased at an exponential rate. Meanwhile, we don’t have a supply of new antibiotics in the pipeline to replace those that are no longer effective. In the last 30 years no major new types of antibiotics have been developed.”

Superbugs are not the stuff of science fiction. The World Health Organization (WHO) declared that antibiotic resistance is one of the major health threats of the twenty-first century. In February 2017, they released a list of the 12 families of bacteria that pose the greatest threat to human health, and called for governments to invest in new drug development to combat them.

Infection's molecular mechanisms

From identifying antibiotic alternatives in agriculture to developing new compounds that block key bacterial targets, our scientists are working on AMR from a host of different angles. Dr Heras specialises in investigating the molecular mechanisms underlying Gram-negative bacterial infections. She focuses on pathogens classified as critical or high priority on the WHO list, including Escherichia coli, Salmonella enterica and Neisseria ssp., which cause infections such as pneumonia, diarrhoea, meningitis, urinary tract infections, gonorrhoea and sepsis.

“We focus on developing anti-virulence agents that tackle virulence but not viability,” Dr Heras explains. “Virulence proteins are the collective weaponry bacteria use to establish an infection and cause disease. My team uses a multidisciplinary approach combining X-ray crystallography, extensive biophysical techniques, immunoassays and cellular assays to determine what virulence proteins look like and to understand how they function.”

“We then use this information to develop inhibitors that disarm pathogens without destroying them, thereby reducing the selection pressure and the development of AMR. For example, we have recently developed molecules that block the ability of some Escherichia coli strains to form biofilms, which cause chronic infections as well as infections related to the use of medical devices.”

“I am passionate about understanding, in atomic detail, how bacteria use sophisticated mechanisms to cause infection,” added Dr Heras. “The greatest achievement for me would be to translate this knowledge to the development of new therapeutics.”

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