Resolving colistin resistance and heteroresistance in Enterobacter species
Abstract: Species within the Enterobacter cloacae complex (ECC) include globally important nosocomial pathogens. A three-year study of ECC in Germany identified Enterobacter xiangfangensis as the most common species (65.5%) detected, a result replicated by examining a global pool of 3246 isolates. Antibiotic resistance profiling revealed widespread resistance and heteroresistance to the antibiotic colistin and detected the mobile colistin resistance (mcr)−9 gene in 19.2% of all isolates. We show that resistance and heteroresistance properties depend on the chromosomal arnBCADTEF gene cassette whose products catalyze transfer of L-Ara4N to lipid A. Using comparative genomics, mutational analysis, and quantitative lipid A profiling we demonstrate that intrinsic lipid A modification levels are genospecies-dependent and governed by allelic variations in phoPQ and mgrB, that encode a two-component sensor-activator system and specific inhibitor peptide. By generating phoPQ chimeras and combining them with mgrB alleles, we show that interactions at the pH-sensing interface of the sensory histidine kinase phoQ dictate arnBCADTEF expression levels. To minimize therapeutic failures, we developed an assay that accurately detects colistin resistance levels for any ECC isolate
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Nature communications. - 14, 1 (2023) , 140, ISSN: 2041-1723
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
-
Universität
- (when)
-
2023
- Creator
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Doijad, Swapnil Prakash
Gisch, Nicolas
Gölz, Hanna
Häcker, Georg
Kern, Winfried V.
Chakraborty, Trinad
Vavra, Martina
Schuster, Sabine
Peyerl-Hoffmann, Gabriele
Hamprecht, A.
- DOI
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10.1038/s41467-022-35717-0
- URN
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urn:nbn:de:bsz:25-freidok-2332374
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
14.08.2025, 10:50 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Doijad, Swapnil Prakash
- Gisch, Nicolas
- Gölz, Hanna
- Häcker, Georg
- Kern, Winfried V.
- Chakraborty, Trinad
- Vavra, Martina
- Schuster, Sabine
- Peyerl-Hoffmann, Gabriele
- Hamprecht, A.
- Universität
Time of origin
- 2023
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