Antibiotic potentiation and inhibition of cross-resistance in pathogens associated with cystic fibrosis.

Autor:	Kadeřábková N; Department of Molecular Biosciences, The University of Texas at Austin, Austin, 78712, Texas, USA.; Centre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK., Furniss RCD; Centre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK., Maslova E; Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK., Eisaiankhongi L; Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK., Bernal P; Departamento de Microbiología, Facultad de Biología, Universidad de Sevilla, Seville, 41012, Spain., Filloux A; Centre for Bacterial Resistance Biology, Department of Life Sciences, Imperial College London, London, SW7 2AZ, UK.; Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, 637551, Singapore., Landeta C; Department of Biology, Indiana University, Bloomington, Indiana, 47405, USA., Gonzalez D; Laboratoire de Microbiologie, Institut de Biologie, Université de Neuchâtel, Neuchâtel, 2000, Switzerland., McCarthy RR; Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK., Mavridou DAI; Department of Molecular Biosciences, The University of Texas at Austin, Austin, 78712, Texas, USA.; John Ring LaMontagne Center for Infectious Diseases, The University of Texas at Austin, Austin, 78712, Texas, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Aug 02. Date of Electronic Publication: 2023 Aug 02.
DOI:	10.1101/2023.08.02.551661
Abstrakt:	Critical Gram-negative pathogens, like Pseudomonas , Stenotrophomonas and Burkholderia , have become resistant to most antibiotics. Complex resistance profiles together with synergistic interactions between these organisms increase the likelihood of treatment failure in distinct infection settings, for example in the lungs of cystic fibrosis patients. Here, we discover that cell envelope protein homeostasis pathways underpin both antibiotic resistance and cross-protection in CF-associated bacteria. We find that inhibition of oxidative protein folding inactivates multiple species-specific resistance proteins. Using this strategy, we sensitize multi-drug resistant Pseudomonas aeruginosa to β-lactam antibiotics and demonstrate promise of new treatment avenues for the recalcitrant pathogen Stenotrophomonas maltophilia . The same approach also inhibits cross-protection between resistant S. maltophilia and susceptible P. aeruginosa , allowing eradication of both commonly co-occurring CF-associated organisms. Our results provide the basis for the development of next-generation strategies that target antibiotic resistance, while also impairing specific interbacterial interactions that enhance the severity of polymicrobial infections. Competing Interests: DECLARATION OF INTERESTS: The authors declare no competing interests.
Databáze:	MEDLINE
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