Work

Uncovering Scaling Laws to Infer Multidrug Response of Resistant Microbes and Cancer Cells

Year: 2014

Type: article

Abstract: Drug resistance in bacterial infections and cancers constitutes a major threat to human health. Treatments often include several interacting drugs, but even potent therapies can become ineffective in resistant mutants. Here, we simplify the picture of drug resistance by identifying scaling laws that unify the multidrug responses of drug-sensitive and -resistant cells. On the basis of these scaling relationships, we are able to infer the two-drug response of resistant mutants in previously unsampled regions of dosage space in clinically relevant microbes such as E. coli, E. faecalis, S. aureus, and S. cerevisiae as well as human non-small-cell lung cancer, melanoma, and breast cancer stem cells. Importantly, we find that scaling relations also apply across evolutionarily close strains. Finally, scaling allows one to rapidly identify new drug combinations and predict potent dosage regimes for targeting resistant mutants without any prior mechanistic knowledge about the specific resistance mechanism.

Source: Cell Reports

DOI: 10.1016/j.celrep.2014.02.007

Authors: Kevin B. Wood, Kris C. Wood, Satoshi Nishida, Philippe Cluzel

Institutions: Harvard University, Center for Systems Biology, Whitehead Institute for Biomedical Research

Language: English

Topic: Antibiotic Resistance in Bacteria

Subfield: Molecular Medicine

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,438