Collaborators from the University of Cambridge and the Wellcome Sanger Institute suggests that some MRSA infections could be solved using widely-used antibiotics.
Medicine and healthcare have been revolutionized through the introduction of antibiotics in treating infections. One of the concerns involve bacteria in developing resistance because of drug use and misuse. Modern medicine is greatly concerned with a few antibiotics in development due to antibiotic resistance that could increase the number of untreatable infections.
Penicillin and penicillin derivatives are some of the widespread and clinically significant groups of antibiotics. Beta-lactase, an enzyme, is responsible for the first kind of penicillin resistance. This led manufacturers to develop new penicillin derivatives, such as methicillin, which were beta-lactamase resistant.
Methicillin-resistant Staphylococcus aureus -MRSA- is one kind of bacteria that has developed resistance to this class of drugs. Hospitals and communities find it problematic when it comes to treating MRSA.
"In previous research, a team of researchers in Cambridge identified an isolate of MRSA (a sample grown in culture from a patient's infection) that showed susceptibility to penicillin in combination with clavulanic acid. Clavulanic acid is a beta-lactamase inhibitor, which prevents the beta-lactamase enzyme from destroying penicillin; it is already used as a medicine to treat kidney infections during pregnancy," according to Eureka Alert.
International collaborators used genome sequencing technology in identifying which genes make MRSA prone to this combination of drugs. A protein known as a penicillin-binding protein 2a or PBP2a is the center of various mutations.
The significance of PBP2a in MRSA strains can never be underestimated because it allows the growth of the presence of penicillin and penicillin derivatives. PBP2a expression has been reduced as well as increasing the binding ability of penicillin to PBP2a in the presence of clavulanic acid are the results of these mutations. This combination of penicillin and clavulanic acid results to overcome the resistance of penicillin.
"The team then looked at whole genome sequences of a diverse collection of MRSA strains and found that a significant number of strains - including USA300 clone, the dominant strain in the United States - contained both mutations that confer susceptibility. This means that one of the most widespread strains of MRSA-causing infections could be treatable by a combination of drugs already licensed for use," Eureka Alert reports further.
The two-drug combo was successful in treating MRSA infections in moth larvae and then mice. The researchers plan to conduct clinical trials in humans.
Dr. Mark Holmes from the Department of Veterinary Medicine at the University of Cambridge, a senior author of the study, says: "MRSA and other antibiotic-resistant infections are a major threat to modern medicine and we urgently need to find new ways to tackle them. Developing new medicines is extremely important, but can be a lengthy and expensive process. Our works suggest that already widely-available medicines could be used to treat one of the world's major strains of MRSA."
First author Dr. Ewan Harrison, from the Wellcome Sanger Institute and the University of Cambridge, adds: "This study highlights the importance of genomic surveillance - collecting and sequencing representative collections of bacterial strains. By combining the DNA sequencing data generated by genomic surveillance with laboratory testing of the strains against a broad selection of antibiotics, we may find other unexpected chinks in the armor of antibiotic-resistant bacteria that might give us new treatment options."
Dr. Jessica Boname, Head of Antimicrobial Resistance at the MRC, says: "This study demonstrates how a mechanistic understanding of resistance and access to clinical data can be used to find new ways to contain and control infections with existing resources."
