000124069 001__ 124069
000124069 005__ 20241125101131.0
000124069 0247_ $$2doi$$a10.1128/spectrum.02276-22
000124069 0248_ $$2sideral$$a132531
000124069 037__ $$aART-2023-132531
000124069 041__ $$aeng
000124069 100__ $$aHernando-Amado, S.
000124069 245__ $$aRapid phenotypic convergence towards collateral sensitivity in clinical isolates of Pseudomonas aeruginosa presenting different genomic backgrounds
000124069 260__ $$c2023
000124069 5060_ $$aAccess copy available to the general public$$fUnrestricted
000124069 5203_ $$aCollateral sensitivity (CS) is an evolutionary trade-off by which acquisition of resistance to an antibiotic leads to increased susceptibility to another. This Achilles’ heel of antibiotic resistance could be exploited to design evolution-based strategies for treating bacterial infections. To date, most studies in the field have focused on the identification of CS patterns in model strains. However, one of the main requirements for the clinical application of this trade-off is that it must be robust and has to emerge in different genomic backgrounds, including preexisting drug-resistant isolates, since infections are frequently caused by pathogens already resistant to antibiotics. Here, we report the first analysis of CS robustness in clinical strains of Pseudomonas aeruginosa presenting different ab initio mutational resistomes. We identified a robust CS pattern associated with short-term evolution in the presence of ciprofloxacin of clinical P. aeruginosa isolates, including representatives of high-risk epidemic clones belonging to sequence type (ST) 111, ST175, and ST244. We observed the acquisition of different ciprofloxacin resistance mutations in strains presenting varied STs and different preexisting mutational resistomes. Importantly, despite these genetic differences, the use of ciprofloxacin led to a robust CS to aztreonam and tobramycin. In addition, we describe the possible application of this evolutionary trade-off to drive P. aeruginosa infections to extinction by using the combination of ciprofloxacin-tobramycin or ciprofloxacin-aztreonam. Our results support the notion that the identification of robust patterns of CS may establish the basis for developing evolution-informed treatment strategies to tackle bacterial infections, including those due to antibiotic-resistant pathogens. IMPORTANCE Collateral sensitivity (CS) is a trade-off of antibiotic resistance evolution that could be exploited to design strategies for treating bacterial infections. Clinical application of CS requires it to robustly emerge in different genomic backgrounds. In this study, we performed an analysis to identify robust patterns of CS associated with the use of ciprofloxacin in clinical isolates of P. aeruginosa presenting different mutational resistomes and including high-risk epidemic clones (ST111, ST175, and ST244). We demonstrate the robustness of CS to tobramycin and aztreonam and the potential application of this evolutionary observation to drive P. aeruginosa infections to extinction. Our results support the notion that the identification of robust CS patterns may establish the basis for developing evolutionary strategies to tackle bacterial infections, including those due to antibiotic-resistant pathogens.
000124069 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/RD16-0016-0004$$9info:eu-repo/grantAgreement/ES/ISCIII/RD16-0016-0011$$9info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2020-113521RB-I00$$9info:eu-repo/grantAgreement/ES/MINECO/SEV-2017-0712
000124069 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000124069 590__ $$a3.7$$b2023
000124069 592__ $$a1.028$$b2023
000124069 591__ $$aMICROBIOLOGY$$b61 / 161 = 0.379$$c2023$$dQ2$$eT2
000124069 593__ $$aImmunology and Microbiology (miscellaneous)$$c2023$$dQ1
000124069 593__ $$aInfectious Diseases$$c2023$$dQ1
000124069 593__ $$aPhysiology$$c2023$$dQ1
000124069 593__ $$aEcology$$c2023$$dQ1
000124069 593__ $$aGenetics$$c2023$$dQ2
000124069 593__ $$aMicrobiology (medical)$$c2023$$dQ2
000124069 593__ $$aCell Biology$$c2023$$dQ2
000124069 594__ $$a3.2$$b2023
000124069 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000124069 700__ $$aLópez-Causapé, C.
000124069 700__ $$aLaborda, P.
000124069 700__ $$aSanz-García, F.$$uUniversidad de Zaragoza
000124069 700__ $$aOliver, A.
000124069 700__ $$aMartínez, J. L.
000124069 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000124069 773__ $$g11, 1 (2023), e02276 [15 pp.]$$pMicrobiol. spectr.$$tMicrobiology Spectrum$$x2165-0497
000124069 8564_ $$s2227586$$uhttps://zaguan.unizar.es/record/124069/files/texto_completo.pdf$$yVersión publicada
000124069 8564_ $$s2459940$$uhttps://zaguan.unizar.es/record/124069/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000124069 909CO $$ooai:zaguan.unizar.es:124069$$particulos$$pdriver
000124069 951__ $$a2024-11-22-11:59:08
000124069 980__ $$aARTICLE