Boer Deng
Aug 1, 2015
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Journal
Nature Medicine
Abstract
VOLUME 21 | NUMBER 8 | AUGUST 2015 NATURE MEDICINE In the world of antibiotic resistance, it is well known that bacteria can pass down genetic traits that enable them to dodge the effects of drugs. But they also have an innate, insidious defense option: sometimes, even without any genetic mutation to stave off antimicrobial agents, bacteria simply go to sleep. In this scenario, they become what are known as ‘persisters’—dormant cells with low levels of metabolic activity. In this state, they are rendered untreatable by conventional antibiotics. This phenomenon of persistence might explain why tuberculosis is so hard to cure1, and why biofilms—thin conglomerates of bacterial cells that form on many surfaces and contain persister cells—form on wounds, causing chronic infections that cost hospitals some $25 billion a year in the US alone2. Up to 80% of all infections in the body are thought to result from biofilms, according to the US National Institutes of Health in Bethesda, Maryland. Researchers are trying numerous ways to kill off these hardy, tricky-to-identify cells. Since April, several groups have reported an encouraging approach. Their solution is to borrow from a mechanism that is already well known in cancer treatment: adding a drug that fuses itself to parts of a cell’s DNA so that the DNA cannot encode proteins, stopping all cell function. Two research groups have independently seen success at killing persisters using mitomycin C, a chemotherapeutic agent that has been used as a therapy in humans against stomach, bladder and other cancers since the 1960s. The drug works by chemically fusing together individual nucleic acids, rendering DNA strands inseparable. Cross-linking DNA this way stops even the low levels of cell function that are exhibited by dormant tumor cells. In May, antibiotics researcher Kim Lewis of Northeastern University in Boston reported using mitomycin C successfully to kill both persistent and active cells of the Lyme disease– causing microbe Borrelia burgdorferi3. In his study, Lewis cultured the bacteria until slowmetabolizing persisters of the B. burgdorferi cells formed. In addition to mitomycin C, he doused the B. burgdorferi cells with a slew of commonly used antibiotic drugs—amoxicillin, vancomycin, ceftriaxone, spectinomycin, doxycycline and gemifloxacin. He found that only mitomycin C could eradicate all B. burgdorferi cells. “Persisters of Borrelia are really hard to kill,” Lewis says. But mitomycin Problem of persisters persists, but anti-cancer drugs hold hope