PT  - JOURNAL ARTICLE
AU  - Hannah R. Meredith
AU  - Virgile Andreani
AU  - Allison J. Lopatkin
AU  - Anna J. Lee
AU  - Deverick J. Anderson
AU  - Gregory Batt
AU  - Lingchong You
TI  - Dissecting bacterial resistance and resilience in antibiotic responses
AID  - 10.1101/305482
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 305482
4099  - http://biorxiv.org/content/early/2018/04/20/305482.short
4100  - http://biorxiv.org/content/early/2018/04/20/305482.full
AB  - An essential property of microbial communities is the ability to survive a disturbance. Survival can be achieved through resistance, the ability to absorb effects of a disturbance without a significant change, or resilience, the ability to recover after being perturbed by a disturbance. These concepts have long been applied to the analysis of ecological systems, though their interpretations are often subject to debate. Here we show that this framework readily lends itself to the dissection of the bacterial response to antibiotic treatment, where both terms can be unambiguously defined. The ability to tolerate the antibiotic treatment in the short term corresponds to resistance, which primarily depends on traits associated with individual cells. In contrast, the ability to recover after being perturbed by an antibiotic corresponds to resilience, which primarily depends on traits associated with the population. This framework effectively reveals the phenotypic signatures of bacterial pathogens expressing extended spectrum β-lactamases (ESBLs), when treated by a β-lactam antibiotic. Our analysis has implications for optimizing treatment of these pathogens using a combination of a β-lactam and a β-lactamase (Bla) inhibitor. In particular, our results underscore the need to dynamically optimize combination treatments based on the quantitative features of the bacterial response to the antibiotic or the Bla inhibitor.