Antibiotic resistance has been increasing for the past few years, imposing a threat to human health. Due to antibiotic resistance, many bacteria are no longer vulnerable to conventional antibiotics. Further, the existing research on antibiotics isn’t enough to combat advanced genetically mutated bacterial infections.
As a solution, researchers at the University of Queensland, Australia, have developed a novel experimental antibiotic, MCC5145, that can neutralise bacterial infections such as Methicillin-resistant Staphylococcus aureus (MRSA) in mice. Human trials are still pending but, it is a big move against antibacterial resistance.
How common is antibacterial drug resistance?
According to the Centre for Disease Control and Prevention (CDC), more than 2.8 million antimicrobial-resistant infections occur in the U.S. each year, and more than 35000 people succumb to these infections. Scientists have been working on developing drugs, but most of them focus on treating infections due to Gram-negative bacteria which cause a majority of infections, such as pneumonia, surgical site or wound infections, bloodstream infections, etc., Gram-positive bacteria like MRSA or streptococci cause infections, and toxic shock.
How did researchers develop the new antibiotic drug?
The new antibiotic drug is a modified version of vancomycin – a glycopeptide (glycogen and protein) antibiotic used to treat various bacterial infections. Researchers tested various forms of vancomycin by modifying the chemical structure of each drug form.
To test the drug’s efficacy, researchers went through multiple clinical trials. First, they injected bacteria causing MRSA and other infections into mice. Then, they dosed them with MCC5145 antibiotic to see its effects.
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What did researchers find?
The researchers saw that the antibiotic showed excellent potential against Methicillin-resistant Staphylococcus aureus (MRSA) and other gram-positive bacterial infections. It showed therapeutic efficacy when injected into mice through the skin. Compared to the original vancomycin drug, MCC5145 exhibited reduced neurotoxicity (toxicity in the kidneys). Further, it showed improved activity against biofilms than vancomycin. Biofilms are a collection of multiple types of microorganisms that can grow on different surfaces. Bacteria form biofilms to protect themselves from antibiotics and flourish within the living body. Overall, the antibiotic decreased the drug resistance ability of gram-positive bacteria when given to mice.
To gain better insights into the research, we interviewed Dr Mark Blaskovich (DMB), the lead author of the study.
CTS: Why developing antibiotics against gram-positive bacteria has been difficult for scientists?
DMB: The rise in antimicrobial resistance and decline in the development of new antibiotics means that the advancement of ANY new antibiotic, Gram-positive or negative, has proved challenging, primarily due to a lack of funding. Much of the focus in recent years has been on the need for new Gram-negative antibiotics, as they tend to be more difficult to kill, and there are not as many new options in the pipeline. However, as highlighted in a publication earlier this year that measured deaths due to antimicrobial resistance in 2019, our existing treatments for Gram-positive infections are not always effective, with 2 Gram-positive bacteria (Staphylococcus aureus and Streptococcus pneumoniae) in the top 4 species of bacteria causing death. Indeed, methicillin-resistant S. aureus (MRSA, or ‘golden staph’) was the most common resistant species/antibiotic combination. We need to come up with better treatment options.
CTS: What challenges did you face while experimenting with living organisms?
DMB: Some of the bacteria we work with are a bit nasty, so we do take extra care in handling them. Animal studies in mice and rats are often very specialised, which is one of the reasons we have so many collaborators on the paper. We contacted researchers with expertise in the different types of studies done, such as the biofilm infection model in Basel, bioluminescent bacteria infection models in Adelaide and California, a Lyme disease model in Boston and a C. difficile model in Melbourne. Their willingness to participate in the research is a great example of how we need to work together to overcome antimicrobial resistance.
CTS: What are your expectations with this new antibiotic?
DMB: We think that this antibiotic has potential advantages over the existing therapies being used, particularly with its potency against a wide range of strains of Gram-positive bacteria, and its activity against biofilms. The genetic studies done on bacteria treated with the antibiotic indicate that it has subtle differences in how it kills the bacteria compared to other antibiotics from the same class. However, it’s at a stage now where it needs a substantial investment in money to do the final tests that would allow it to be tested in humans, and some entity to carry it forward into clinical trials. Ideally, we’d find a partner who would licence it and carry it forward.
The detailed study has been published in the journal Science Translational Medicine.