PT  - JOURNAL ARTICLE
AU  - Hernando-Amado, Sara
AU  - Sanz-García, Fernando
AU  - Martínez, José Luis
TI  - Rapid and robust evolution of collateral sensitivity in <em>Pseudomonas aeruginosa</em> antibiotic-resistant mutants
AID  - 10.1126/sciadv.aba5493
DP  - 2020 Aug 01
TA  - Science Advances
PG  - eaba5493
VI  - 6
IP  - 32
4099  - http://advances.sciencemag.org/content/6/32/eaba5493.short
4100  - http://advances.sciencemag.org/content/6/32/eaba5493.full
SO  - Sci Adv2020 Aug 01; 6
AB  - The analysis of trade-offs, as collateral sensitivity, associated with the acquisition of antibiotic resistance, is mainly based on the use of model strains. However, the possibility of exploiting these trade-offs for fighting already resistant isolates has not been addressed in depth, despite the fact that bacterial pathogens are frequently antibiotic-resistant, forming either homogeneous or heterogeneous populations. Using a set of Pseudomonas aeruginosa-resistant mutants, we found that ceftazidime selects pyomelanogenic tobramycin-hypersusceptible mutants presenting chromosomal deletions in the analyzed genetic backgrounds. Since pyomelanogenic resistant mutants frequently coexist with other morphotypes in patients with cystic fibrosis, we analyzed the exploitation of this trade-off to drive extinction of heterogeneous resistant populations by using tobramycin/ceftazidime alternation. Our work shows that this approach is feasible because phenotypic trade-offs associated with the use of ceftazidime are robust. The identification of conserved collateral sensitivity networks may guide the rational design of evolution-based antibiotic therapies in P. aeruginosa infections.