Paranoid Bacteria Maintain Antibiotic Resistant Posture

    “It’s not paranoia if they’re really out to get you.” These are words to live by—or rather, infect by, provided you’re part of a bacterial population.

    While it’s one thing for bacteria to enter a transient, drug-tolerant state while they are under antibiotic attack, it’s quite another for bacteria to enter such a state when they are unmolested. And yet some bacteria within “safe” bacterial populations adopt an antibiotic-resistant posture, even though doing so would seem unnecessary, even wasteful.

    This finding, which emerged from research conducted at the University of Vermont, could explain how bacterial populations are able to sustain persistent infections. It suggests that bacteria cooperate at the population level to hedge against the sudden appearance of an antibiotic.

    The finding may also have practical implications. For example, it indicates that the frequency and timing of antibiotic treatment could be a way of waiting out an infection, killing off bacterial subpopulations as they exit their transient drug-resistant states, and eradicating entire bacterial cultures.

    The University of Vermont researchers, led by Mary Dunlop, Ph.D., investigated a particular kind of transient resistance—the generation of protein cascades. This kind of resistance, which is instigated by the multiple antibiotic resistance activator, MarA, has been known to arise among all the cells within a bacterial population that is under antibiotic attack. Dr. Dunlop and colleagues, however, wanted to know whether MarA expression also has a stochastic component, even when uninduced.

    This question was addressed by Dr. Dunlop’s team January 13 in the journal Scientific Reports, in an article entitled, “Stochastic expression of a multiple antibiotic resistance activator confers transient resistance in single cells.” The article used time-lapse microscopy to demonstrate that bacterial colonies use the protein cascade strategy even when they are not under threat.

    “Time-lapse microscopy showed that isogenic cells express heterogeneous, dynamic levels of MarA, which were correlated with transient antibiotic survival,” wrote the authors. “This finding has important clinical implications, as stochastic expression of resistance genes may be widespread, allowing populations to hedge against the sudden appearance of an antibiotic.”

    “This transient resistance, distributed in varying degrees among individual cells in a population, may be the norm for many bacterial populations,” said Dr. Dunlop.

    Some antibiotic-resistant bacteria, such as MRSA, are resistant due to genetic changes such as mutations. Those studied by Dunlop are her colleagues alter their traits—protein expression, for instance—but not their genomes, making them significantly more difficult to identify because the resistance level of each bacterium changes over time.

    “It’s costly from a metabolic standpoint for a cell to express the proteins that enable it to be resistant,” Dr. Dunlop continued. “This strategy allows a colony to hedge its bets by enabling individual cells within a population to assume high levels of resistance while others avoid this extra work.”