Despite concerted efforts to curb the indiscriminate prescription of antimicrobials, drug-resistant microorganisms persist, and it is becoming clear that the resolution of this public health problem will not be achieved by a reduction in antibiotic use alone. Rather, the problem of drug resistance calls for a broader approach that takes into account the complexities of microbial physiology and the fitness benefits that are conferred to the pathogen by antibiotic-resistance proteins. In this month's journal, we feature two articles that discuss this topical issue. On page 566, Eitan Bibi and colleagues provide support for the argument that factors other than antibiotic selection can promote the persistence of antibiotic-resistance genes. The authors focus on two antibiotic-efflux transporters, Tet(L) and MdfA, and contend that their persistence is due to their alternative physiological roles in bacterial alkali homeostasis.
On page 547, James Anderson considers the interplay of factors that contribute to the evolution of anti-fungal drug resistance. Here, the fitness effects of combined, synergistic resistance mechanisms are crucial for the maintenance of resistance in fungal populations. On a positive note, the author describes how evolution experiments can be used to predict resistance during the drug-development stage, and he suggests ways in which the evolution of drug resistance can be impaired in fungi.
