Unknown

Dataset Information

0

Defining ICR-Mo, an intrinsic colistin resistance determinant from Moraxella osloensis.


ABSTRACT: Polymyxin is the last line of defense against severe infections caused by carbapenem-resistant gram-negative pathogens. The emergence of transferable MCR-1/2 polymyxin resistance greatly challenges the renewed interest in colistin (polymyxin E) for clinical treatments. Recent studies have suggested that Moraxella species are a putative reservoir for MCR-1/2 genetic determinants. Here, we report the functional definition of ICR-Mo from M. osloensis, a chromosomally encoded determinant of colistin resistance, in close relation to current MCR-1/2 family. ICR-Mo transmembrane protein was prepared and purified to homogeneity. Taken along with an in vitro enzymatic detection, MALDI-TOF mass spectrometry of bacterial lipid A pools determined that the ICR-Mo enzyme might exploit a possible "ping-pong" mechanism to accept the phosphoethanolamine (PEA) moiety from its donor phosphatidylethanolamine (PE) and then transfer it to the 1(or 4')-phosphate position of lipid A via an ICR-Mo-bound PEA adduct. Structural decoration of LPS-lipid A by ICR-Mo renders the recipient strain of E. coli resistant to polymyxin. Domain swapping assays indicate that the two domains of ICR-Mo cannot be functionally-exchanged with its counterparts in MCR-1/2 and EptA, validating its phylogenetic position in a distinct set of MCR-like genes. Structure-guided functional mapping of ICR-Mo reveals a PE lipid substrate recognizing cavity having a role in enzymatic catalysis and the resultant conference of antibiotic resistance. Expression of icr-Mo in E. coli significantly prevents the formation of reactive oxygen species (ROS) induced by colistin. Taken together, our results define a member of a group of intrinsic colistin resistance genes phylogenetically close to the MCR-1/2 family, highlighting the evolution of transferable colistin resistance.

SUBMITTER: Wei W 

PROVIDER: S-EPMC5983563 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

2018-01-01 | S-EPMC5893884 | BioStudies
2018-01-01 | S-EPMC5868246 | BioStudies
2018-01-01 | S-EPMC6116419 | BioStudies
2017-01-01 | S-EPMC5424208 | BioStudies
2020-01-01 | S-EPMC6910190 | BioStudies
2018-01-01 | S-EPMC6197822 | BioStudies
2018-01-01 | S-EPMC5869126 | BioStudies
2017-01-01 | S-EPMC5700323 | BioStudies
2018-01-01 | S-EPMC6693033 | BioStudies
2019-01-01 | S-EPMC6347640 | BioStudies