Universität zu Köln

Roemhild, Roderich ORCID: 0000-0001-9480-5261, Bollenbach, Tobias ORCID: 0000-0003-4398-476X and Andersson, Dan I. (2022). The physiology and genetics of bacterial responses to antibiotic combinations. Nat. Rev. Microbiol., 20 (8). S. 478 - 491. BERLIN: NATURE PORTFOLIO. ISSN 1740-1534

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Abstract

Combining several antibiotics, either in mixtures or sequential order, is proposed to increase treatment efficacy and reduce resistance evolution. In this Review, Andersson and colleagues discuss the effects of antibiotic combinations, the directional effects of previous antibiotic treatments and the role of stress-response systems as well as the interactions between drugs and resistance mutations. Several promising strategies based on combining or cycling different antibiotics have been proposed to increase efficacy and counteract resistance evolution, but we still lack a deep understanding of the physiological responses and genetic mechanisms that underlie antibiotic interactions and the clinical applicability of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological stress responses and emerging resistance mutations (occurring at different time scales) generate complex and often unpredictable dynamics. In this Review, we present our current understanding of bacterial cell physiology and genetics of responses to antibiotics. We emphasize recently discovered mechanisms of synergistic and antagonistic drug interactions, hysteresis in temporal interactions between antibiotics that arise from microbial physiology and interactions between antibiotics and resistance mutations that can cause collateral sensitivity or cross-resistance. We discuss possible connections between the different phenomena and indicate relevant research directions. A better and more unified understanding of drug and genetic interactions is likely to advance antibiotic therapy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Roemhild, Roderich UNSPECIFIED orcid.org/0000-0001-9480-5261 UNSPECIFIED Bollenbach, Tobias UNSPECIFIED orcid.org/0000-0003-4398-476X UNSPECIFIED Andersson, Dan I. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-672950
DOI:	10.1038/s41579-022-00700-5
Journal or Publication Title:	Nat. Rev. Microbiol.
Volume:	20
Number:	8
Page Range:	S. 478 - 491
Date:	2022
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	1740-1534
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language 2-COMPONENT REGULATORY SYSTEM; ENVELOPE STRESS-RESPONSE; CELL-WALL DAMAGE; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; BACILLUS-SUBTILIS; SOS RESPONSE; SUBINHIBITORY CONCENTRATIONS; EFFLUX PUMP; DNA GYRASE Multiple languages Microbiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67295