Generation and Treatment of Antibiotic Resistance

Bacteria can transfer genes conferring antibiotic resistance among strains infecting a single patient. To combat antibiotic resistance, researchers screened for drugs that can be repurposed to amplify the activity of existing antibiotics and inhibit resistant bacteria.

Antibiotics are responsible for the most significant increase in lifespan in human history. However, microbes are becoming resistant to antibiotics at an alarming rate. For example, uncontrolled drug-resistant infections can lead to recurrent urinary tract infections, sepsis, and even death. The Mulvey lab found that microbes within a single colonized site, such as the human bladder, can pass antibiotic resistance genes back and forth, propagating resistance as the infecting microbes evolve in response to serial antibiotic treatment. To improve potential treatments, the Brown lab developed methods to rapidly identify drugs that interact with existing antibiotics to increase drug efficacy. Exploiting these potentiating interactions between existing drugs allows us to expand our drug repertoire by drug repurposing – using drugs already approved by the FDA for other indications – which bypasses expensive and time-consuming clinical trials.

References:

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High-throughput identification and rational design of synergistic small-molecule pairs for combating and bypassing antibiotic resistance. Wambaugh MA, Shakya VPS, Lewis AJ, Mulvey MA, Brown JCS. PLoS Biol. 2017 Jun;15(6):e2001644.

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Population dynamics of an Escherichia coli ST131 lineage during recurrent urinary tract infection. Forde BM, Roberts LW, Phan MD, Peters KM, Fleming BA, Russell CW, Lenherr SM, Myers JB, Barker AP, Fisher MA, Chong TM, Yin WF, Chan KG, Schembri MA, Mulvey MA, Beatson SA. Nat Commun. 2019 Aug;10(1):3643.

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