Image: Sun et al, HKU

A combined treatment against antibiotic resistance

23 September 2023

Professor Sun Hongzhe (Croucher Senior Research Fellow 2010) and colleagues at the University of Hong Kong have found that a combination of the antibiotic cefiderocol and metal compounds like colloidal bismuth citrate can effectively fight drug-resistant bacteria such as Pseudomonas aeruginosa and Burkholderia cepacia. This combination was found to improve the performance of cefiderocol and reduce the chances of bacteria developing resistance.

Cefiderocol is a type of antibiotic known as a sideromycin, approved for use against severe drug-resistant infections. However, bacteria are beginning to develop resistance to it, making new solutions necessary. Sun and his colleagues  showed that using colloidal bismuth citrate and cefiderocol together can increase the survival rate of mice with severe pneumonia and reduce the number of bacteria in their lungs. The research was published in Nature Communications.

Sideromycins work by entering bacterial cells through active transport pathways. This method uses the bacteria’s nutrient uptake pathways to bypass its defenses. However, as resistance to sideromycins like cefiderocol inevitablygrows, other strategies will be needed.

One promising approach involves using metal compounds as antimicrobial agents. These agents, like bismuth(III) and gallium(III), can disrupt the functions of ferric iron (Fe3+), a nutrient bacteria need to survive. By combining these compounds with sideromycins, Sun and his colleagues discovered that they could slow the development of antibiotic resistance.

“We are short of new antibiotics, and infection caused by resistant bacteria may lead to another pandemic. We have uncovered a dual Trojan Horse strategy to restore antibiotics activity, such as cefiderocol, and hope to provide a novel arsenal for combating antimicrobial resistance,” said Sun.

In tests, combinations of Bi3+/Ga3+ compounds and cefiderocol proved effective against cefiderocol-resistant strains of bacteria. The combined treatment also showed promise in preventing the development of resistance, potentially extending the useful lifespan of cefiderocol.

This research suggests that metallo-sideromycins like the combination of CBS and cefiderocol could be a valuable tool in the fight against antibiotic resistance. This approach could lead to new treatments for drug-resistant bacterial infections.

To see Professor Sun Hongzhe’s Croucher profile click here.