Journal article
Systematic investigation of resistance evolution to common antibiotics reveals conserved collateral responses across common human pathogens
Bacterial Synthetic Biology, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark1
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark2
PROSYS - Process and Systems Engineering Centre, Department of Chemical and Biochemical Engineering, Technical University of Denmark3
Department of Chemical and Biochemical Engineering, Technical University of Denmark4
As drug resistance continues to grow, treatment strategies that turn resistance into a disadvantage for the organism will increasingly be relied upon to treat infections and to slow the rate of multidrug resistance. The majority of work in this area has investigated how resistance evolution toward a single antibiotic effects a specific organism's collateral response to a wide variety of antibiotics.
Results of these studies have been used to identify networks of drugs which can be used to drive resistance in a particular direction. However, little is known about the extent of evolutionary conservation of these responses across species. We sought to address this knowledge gap by performing a systematic resistance evolution study of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae) under uniform growth conditions using five clinically relevant antibiotics with diverse modes of action.
Evolved lineages were analyzed for collateral effects and the molecular mechanisms behind the observed phenotypes. Fourteen universal cross-resistance and two global collateral sensitivity relationships were found among the lineages. Genomic analyses revealed drug dependent divergent and conserved evolutionary trajectories amongst the pathogens.
Our findings suggest that collateral responses may be preserved across species. These findings may help extend the contribution of previous collateral network studies in the development of treatment strategies to address the problem of antibiotic resistance.
Language: | English |
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Publisher: | American Society for Microbiology |
Year: | 2021 |
Pages: | e01273-20-e01273-20 |
ISSN: | 10986596 , 00664804 and 10706283 |
Types: | Journal article |
DOI: | 10.1128/AAC.01273-20 |
ORCIDs: | Sommer, Morten O- A. , Rodriguez de Evgrafov, Mari and Asimakopoulos, Konstantinos |