Antibiotic resistance refers to the ability of bacteria or other microorganisms to withstand the effects of antibiotics that were originally effective against them. It is a natural and evolutionary process that occurs when bacteria mutate or acquire genes that enable them to survive and proliferate in the presence of antibiotics.
A group of researchers from Trinity College Dublin have discovered high-resolution structural insights into a crucial bacterial enzyme that could aid chemists in creating novel medications to inhibit it and so control disease-causing microorganisms. Their work is crucial as concerns about the rising levels of antibiotic resistance continue to spread.
The team of researchers, led by Martin Caffrey, Fellow Emeritus in Trinity’s Schools of Medicine and Biochemistry and Immunology, used single particle cryo-electron microscopy and next-generation X-ray crystallography to “look under the bacterial bonnet” and create a molecular blueprint of the full-length enzyme that could be used to create drugs that target any structural flaws.
A number of disease-causing bacteria have developed resistance to a plethora of first-choice drugs used to treat them and, with antimicrobial resistance on the rise in general, the World Health Organization (WHO) has for some time now advised that a post-antibiotic era, in which minor injuries and common infections could prove fatal, is looming.
Martin Caffrey
The enzyme Lnt, which only exists in bacteria and aids in the development of stable cell membranes through which substances are transported into and out of cells, has a huge potential for use as a therapeutic target. This is because any custom medication made to target it should have fewer side effects for patients.
The research has just been published in the journal Science Advances.
Caffrey said, “A number of disease-causing bacteria have developed resistance to a plethora of first-choice drugs used to treat them and, with antimicrobial resistance on the rise in general, the World Health Organization (WHO) has for some time now advised that a post-antibiotic era, in which minor injuries and common infections could prove fatal, is looming.”
“New drugs are therefore badly needed and, while the journey can be a long one from providing a structural blueprint like this to developing a new drug, the precision to which we have resolved this potential target paints something of a ‘bullseye’ on that target.”
