London: Developing chemicals to slow down an enzyme that provides multi-resistance to antibiotics may be the key to reverse antibiotic resistance, results from twin-studies have suggested.
Resistance to antibiotics is becoming increasingly prevalent and threatens to undermine healthcare systems across the globe.
Beta-lactamases are enzymes produced by bacteria, that provide multi-resistance to beta-lactam antibiotics such as penicillins, Cephalosporins, cephamycins, and carbapenems, although carbapenems are relatively resistant to beta-lactamase.
In the first study, researchers from University of Bristol in the UK, defined the relative importance of two mechanisms associated with beta-lactam antibiotic resistance.
In one, bacteria restricts the entry of antibiotics into the cell. In the other, bacteria produce the enzyme beta-lactamase, which destroys any antibiotic that gets into the cell.
The latter was found to be the more important of the two mechanisms.
These findings imply that if chemicals could be developed to inhibit beta-lactamase enzymes, a significant proportion of antibiotic resistance could successfully be reversed, the researchers noted, in the paper published in the Journal of Antimicrobial Chemotherapy.
“Our bacteriology research has further demonstrated that beta-lactamases are the real “Achilles heel” of antibiotic resistance in bacteria that kill thousands of people every year,” said Matthew Avison, reader in Molecular Bacteriology from the varsity.
Building on these findings, researchers in the second study detailed in the journal Molecular Microbiology, studied the effectiveness of two types of beta-lactamase enzyme inhibitor in a Klebsiella pneumoniae — a bacterium known to be highly resistant to common antibiotics.
The researchers found that both avibactam — an inhibitor recently introduced into clinical practice –, and a “bicyclic boronate” inhibitor failed to consistently protect the beta-lactam antibiotic ceftazidime from attack by the beta-lactamase enzyme.
However, when paired with a different beta-lactam antibiotic, aztreonam, the inhibitors worked extremely well.
They also killed Stenotrophomonas maltophilia — one of the most resistant bacteria that causes severe infections in immunocompromised patients and is usually resistant to all beta-lactam antibiotics, the researchers said.
