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A potential drug offers rare promise in the fight against antibiotic-resistant “superbugs” after it successfully targeted a bacterium that causes life-threatening infections in hospital patients, research has shown.
Superbugs have emerged as a leading health threat as antibiotics and other treatments become ineffective through excessive or careless use. While the drug being developed by Swiss pharmaceutical group Roche has been tested on only one type of bacteria, the way it works suggests it could be effective against other microbes — and encourage much-needed research investment in the field.
“We discovered a new way of killing bacteria. You could imagine tweaking the chemistry to address other targets,” said Michael Lobritz, global head of infectious diseases at Roche Pharma Research & Early Development. Lobritz is co-author with experts from Harvard university of the two papers published in Nature on Wednesday.
Roche is conducting phase 1 clinical trials in humans on the candidate drug, which targets a bacterium known as carbapenem-resistant Acinetobacter baumannii, or CRAB. The pathogen, which causes conditions such as sepsis and pneumonia, thrives in hospitals due to its ease of transmission among patients weakened by other illnesses.
The researchers developed a molecule known as a peptide — a building block of proteins — to weaken CRAB’s outer membrane. The peptide did this by stopping the pathogen from carrying a chemical called a lipopolysaccharide that boosts the membrane’s resilience.
CRAB is classed as a priority concern by the World Health Organization and an urgent threat by the US Centers for Disease Control and Prevention, because of the health risks it poses and the lack of effective treatments for it. No new antibiotic for CRAB has been developed for patient use in more than half a century.
Anti-microbial resistance occurs when bacteria, virus, fungi and parasites evolve the ability to resist existing treatments such as antibiotics. It is already linked to 5mn deaths a year, according to the WHO.
One problem has been the lack of funding for discovery of new drugs as bacterial resistance to older ones has swelled. Many existing drugs derive from natural products, meaning that developing them required less investment in fundamental research than for other kinds of pharmaceuticals.
The anti-CRAB candidate drug, known as zosurabalpin, could be effective against other pathogens that have become resistant to traditional antibiotics and imperil hospital patients, scientists say. These are all part of the same class of so-called Gram-negative bacteria, which have similar outer membrane structures to CRAB.
Zosurabalpin’s emergence “opens the door” to tackling the broader Gram-negative pathogen group, according to Morgan Gugger and Prof Paul Hergenrother of Illinois university, who were not involved in the research. Potential quarry include Pseudomonas aeruginosa and Klebsiella pneumoniae, which cause blood and lung infections, and Escherichia coli (E-coli), which causes intestinal and urinary tract illnesses.
The highly targeted nature of zosurabalpin’s chemical action might also mean it is less destructive to helpful gut bacteria than most traditional antibiotics, Gugger and Hergenrother wrote in a commentary also published in Nature.
“The movement towards bacterium-specific antibiotics is a new development, and one that can be facilitated by diagnostics that can rapidly identify specific harmful bacteria in infected individuals,” they say.
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