A recent study published in Nature sheds light on an often-neglected side of antibiotic resistance, namely the dynamics of resistance on a population level.  Research typically focuses on the spread of resistance through genetic mutation of bacteria and subsequent evolutionary selection and reproduction.  This study instead focuses on how bacterial populations can develop resistance through a form of altruism, where a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable cells, enhancing the survival capacity of the overall population in stressful environments.

In the study, researchers exposed a strain of E. coli to the antibiotic norfloxacin and discovered that the minimum inhibitory concentration (MIC) of the antibiotic (the amount of the drug necessary to inhibit bacterial growth) increased in the population over time.  This realization prompted a search for a mechanism by which bacteria highly resistant to norfloxacin could increase resistance in other, less resistant bacteria.

That mechanism turned out to be the production of indole, a common metabolic product, but one that is typically inhibited by the stress caused by antibiotics.  Because highly resistant bacteria contained genetic mutations which excluded them from norfloxacin-induced stress, they continued to produce indole.  While the indole itself did not directly cause resistance, it nevertheless acted as a signaling mechanism, triggering important processes within the less resistant bacteria, including the activation of efflux pumps to expel the drug from bacterial cells.  As a result, weaker bacteria were able to withstand higher doses of norfloxacin in comparison to what they could withstand without the presence of the highly resistant bacteria. Further experimentation led the researchers to conclude that this population-level phenomenon is not drug-specific.

Bacterial population dynamics have implications for how we think about antibiotic resistant infections.  As the study points out, efforts to monitor and combat antibiotic resistance are complicated by these bet-hedging survival strategies and other forms of bacterial cooperation. More research into these community-level interactions could help inform future treatment practices and interventions.

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