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Volume 24
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10.3390/ijms24086892
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Article

Collateral Sensitivity to Fosfomycin of Tobramycin-Resistant Mutants of Pseudomonas aeruginosa Is Contingent on Bacterial Genomic Background

by
Roberta Genova
1,2,
Pablo Laborda
1,3,4,
Trinidad Cuesta
1,
José Luis Martínez
1,* and
Fernando Sanz-García
1,5,*
1
Centro Nacional de Biotecnología, CSIC, 28043 Madrid, Spain
2
Department of Biotechnology and Environmental Protection, Estación Experimental del Zaidín, CSIC, 18008 Granada, Spain
3
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark
4
Department of Clinical Microbiology 9301, Rigshospitalet, 2100 Copenhagen, Denmark
5
Microbiology Department, Medicina Preventiva y Salud Pública, Universidad de Zaragoza, 50009 Zaragoza, Spain
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(8), 6892; https://doi.org/10.3390/ijms24086892
Submission received: 9 February 2023 / Revised: 16 March 2023 / Accepted: 4 April 2023 / Published: 7 April 2023
(This article belongs to the Special Issue Antimicrobial Resistance—New Insights 2.0)
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Abstract

Understanding the consequences in bacterial physiology of the acquisition of drug resistance is needed to identify and exploit the weaknesses derived from it. One of them is collateral sensitivity, a potentially exploitable phenotype that, unfortunately, is not always conserved among different isolates. The identification of robust, conserved collateral sensitivity patterns is then relevant for the translation of this knowledge into clinical practice. We have previously identified a robust fosfomycin collateral sensitivity pattern of Pseudomonas aeruginosa that emerged in different tobramycin-resistant clones. To go one step further, here, we studied if the acquisition of resistance to tobramycin is associated with robust collateral sensitivity to fosfomycin among P. aeruginosa isolates. To that aim, we analyzed, using adaptive laboratory evolution approaches, 23 different clinical isolates of P. aeruginosa presenting diverse mutational resistomes. Nine of them showed collateral sensitivity to fosfomycin, indicating that this phenotype is contingent on the genetic background. Interestingly, collateral sensitivity to fosfomycin was linked to a larger increase in tobramycin minimal inhibitory concentration. Further, we unveiled that fosA low expression, rendering a higher intracellular accumulation of fosfomycin, and a reduction in the expression of the P. aeruginosa alternative peptidoglycan-recycling pathway enzymes, might be on the basis of the collateral sensitivity phenotype.
Keywords: collateral sensitivity; fosfomycin; Pseudomonas aeruginosa; tobramycin; evolution contingency; antibiotic resistance; bacterial evolution collateral sensitivity; fosfomycin; Pseudomonas aeruginosa; tobramycin; evolution contingency; antibiotic resistance; bacterial evolution

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MDPI and ACS Style

Genova, R.; Laborda, P.; Cuesta, T.; Martínez, J.L.; Sanz-García, F. Collateral Sensitivity to Fosfomycin of Tobramycin-Resistant Mutants of Pseudomonas aeruginosa Is Contingent on Bacterial Genomic Background. Int. J. Mol. Sci. 2023, 24, 6892. https://doi.org/10.3390/ijms24086892

AMA Style

Genova R, Laborda P, Cuesta T, Martínez JL, Sanz-García F. Collateral Sensitivity to Fosfomycin of Tobramycin-Resistant Mutants of Pseudomonas aeruginosa Is Contingent on Bacterial Genomic Background. International Journal of Molecular Sciences. 2023; 24(8):6892. https://doi.org/10.3390/ijms24086892

Chicago/Turabian Style

Genova, Roberta, Pablo Laborda, Trinidad Cuesta, José Luis Martínez, and Fernando Sanz-García. 2023. "Collateral Sensitivity to Fosfomycin of Tobramycin-Resistant Mutants of Pseudomonas aeruginosa Is Contingent on Bacterial Genomic Background" International Journal of Molecular Sciences 24, no. 8: 6892. https://doi.org/10.3390/ijms24086892

APA Style

Genova, R., Laborda, P., Cuesta, T., Martínez, J. L., & Sanz-García, F. (2023). Collateral Sensitivity to Fosfomycin of Tobramycin-Resistant Mutants of Pseudomonas aeruginosa Is Contingent on Bacterial Genomic Background. International Journal of Molecular Sciences, 24(8), 6892. https://doi.org/10.3390/ijms24086892

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