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A newly discovered antibiotic holds potential in combating perilous infections triggered by MRSA and other microbes resistant to medication.(Image credit: CDC/ Melissa Dankel)ShareShare by:
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Researchers have announced the finding of the first in an encouraging fresh type of antibiotics — and the discovery was unexpected, since they hadn’t planned to unearth new medications.
The novel antibiotic compound displays encouraging efficacy against infections resistant to drugs, including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium, microbes well-known for eliciting resistant infections among hospitalized individuals.
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However, the group’s initial objective wasn’t the identification of new medications. Conversely, the scientists were examining how a recognized antibiotic, methylenomycin A, is produced by a bacterium in the soil referred to as Streptomyces coelicolor.
Flora and microorganisms synthesize a variety of intricate compounds recognized as secondary metabolites, numerous of which happen to exhibit valuable therapeutic attributes in humans. Grasping how these compounds are manufactured inside these organisms and the means by which they interact with human cells may enable scientists to create potent drugs from these natural substances.
The schematics for generating these diverse biological molecules reside in specific collections of genes, designated “biosynthetic gene clusters.” By eliminating particular genes from these clusters, Alkhalaf and Challis could excise specific enzymes participating in the synthesis of methylenomycin A. This investigation method authorized them to cease the reaction sequence at crucial junctures to scrutinize it more intimately — and it guided them to discern previously unobserved intermediate compounds arising along the course.
This methodical methodology permitted the team to segregate two molecules never previously documented, which they categorized as pre-methylenomycin C and pre-methylenomycin C lactone. Subsequent to deploying a spectrum of techniques to comprehensively characterize the architecture of these compounds, they scrutinized the molecules’ biological action against a selection of bacterial variants.
Pre-methylenomycin C lactone manifested as exceptionally promising. “[It] demonstrates activity against an array of Gram-positive bacteria, encompassing methicillin-resistant Staphylococcus aureus (MRSA) and a strain of Enterococcus faecium resistant to multiple drugs,” Challis and Alkhalaf conveyed to Live Science. “[It] exhibits 100x superior efficacy in eliminating drug-resistant bacteria in comparison to the original antibiotic.”
Yet, perhaps more critically, the novel compound seemingly does not incite antibiotic resistance in the treated strains.
Recurrent contact with antibiotics can instigate the progression of defense mechanisms in certain bacteria, ultimately culminating in drug resistance that renders subsequent infections exceptionally challenging to manage. In a 28-day trial, E. faecium bacteria encountered elevating levels of pre-methylenomycin C lactone, presenting the optimal setting for resistance to surface. However, across that duration, the team detected no shift in the minimal inhibitory concentration — the drug concentration needed to elicit a discernible result. In essence, the antibiotic preserved its infection-combating capability, and the bacteria failed to cultivate any concerning resistance mechanisms.
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Broadening this course of inquiry — encompassing a broader spectrum of bacterial varieties and scrutinizing the medications’ effects over an extended timeframe — will constitute two vital subsequent steps for the team to validate the complete capacity of the fresh molecule.
“It represents a remarkably elegant study, and I believe it underscores a crucial principle: upon isolating novel molecules, one must explore their unique activities,” commented Stephen Cochrane, a medicinal chemist at Queen’s University Belfast in Ireland, uninvolved in this endeavor. Nonetheless, he cautioned that a substantial distinction exists between a compound displaying antibacterial properties and an antibiotic employed to address illness.
“The pivotal hurdle involves translating this into a pragmatic drug — one that endures sufficiently within the body, evades human toxicity, and remains insusceptible to resistance,” he articulated.
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—Antibiotic resistance nullifies previously life-saving medications. Is there a means to reverse this?
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For Alkhalaf and Challis, this direction precisely mirrors their future aspirations. They are currently in partnership with David Lupton, a synthetic chemist at Monash University in Australia, to devise a chemical pathway toward pre-methylenomycin C lactone. This would equip them to synthesize the molecule de novo utilizing chemical synthesis, eliminating reliance on microbial production. Consequently, this would yield augmented quantities of the compound for investigations aimed at elucidating the molecule’s mechanisms and its potential impacts on human cells.
“It would prove advantageous to pinpoint the compound’s biological target(s) within susceptible bacteria and to foster a more thorough comprehension of how structural alterations to the compound influence target interaction and biological activity,” Alkhalaf and Challis stated. Such insight might advise the blueprint of analogous compounds exhibiting even more formidable antibiotic action.
Victoria AtkinsonSocial Links NavigationLive Science Contributor
Victoria Atkinson is a self-employed science reporter, with a focus on chemistry and its association with the natural domain and the realm of human creation. Currently situated in York (UK), she formerly served as a science content creator at the University of Oxford, and subsequently as a member of the Chemistry World editorial staff. Following her transition to freelance work, Victoria broadened her focus to investigate subjects spanning the sciences and has also partnered with Chemistry Review, Neon Squid Publishing, and the Open University, among others. She possesses a DPhil in organic chemistry from the University of Oxford.
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