Dataset Information

Comparative analysis of phosphoethanolamine transferases involved in polymyxin resistance across 10 clinically relevant Gram-negative bacteria.

ABSTRACT: The rapid emergence of Gram-negative 'superbugs' has become a significant threat to human health globally, and polymyxins have become a last-line therapy for these very problematic pathogens. Polymyxins exhibit their antibacterial killing by initial interaction with lipid A in Gram-negative bacteria. Polymyxin resistance can be mediated by phosphoethanolamine (PEA) modification of lipid A, which abolishes the initial electrostatic interaction with polymyxins. Both chromosome-encoded (e.g. EptA, EptB and EptC) and plasmid-encoded (e.g. MCR-1 and MCR-2) PEA transferases have been reported in Gram-negative bacteria; however, their sequence and functional heterogeneity remain unclear. This article reports a comparative analysis of PEA transferases across 10 clinically relevant Gram-negative bacterial species using multiple sequence alignment and phylogenetic analysis. The results show that the pairwise identities among chromosome-mediated EptA, EptB and EptC from Escherichia coli are low, and EptA shows the greatest similarity with MCR-1 and MCR-2. Among PEA transferases from representative strains of 10 clinically relevant species, the catalytic domain is more conserved compared with the transmembrane domain. In particular, PEA acceptor sites and zinc-binding pockets show high conservation between different species, indicating their potential importance for the function of PEA transferases. The evolutionary relationship of MCR-1, MCR-2 and EptA from the 10 selected bacterial species was evaluated by phylogenetic analysis. Cluster analysis illustrates that 325 EptA from 275 strains of 10 species within each individual species are highly conserved, whereas interspecies conservation is low. This comparative analysis provides key bioinformatic information to better understand the mechanism of polymyxin resistance via PEA modification of lipid A.

SUBMITTER: Huang J

PROVIDER: S-EPMC5869126 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Antimicrobial resistance profiling of pathogens helps to identify the emergence of rare or new resistance threats and prioritize possible actions to be taken against them. The analysis of wastewater (WW) can reveal the circulation of antimicrobial-resistant bacteria (ARB) and antimicrobial resistance genes (ARG) among the catchment communities. Here, we analyzed WW influent samples to determine the prevalence of carbapenemase genes-carrying Gram-negative bacteria (Carba-GNB) in Helsinki, Finland. This study set important historical reference points from the very early stage of the carbapenemase era, during the period 2011-2012. A total of 405 bacterial isolates grown on CHROMagarKPC (n = 195) and CHROMagarESBL (n = 210) from WW influent samples were collected between October 2011 and August 2012 and were analyzed. The bacterial DNA from the isolates was extracted, and the prevalence of carbapenemases genes bla KPC, bla NDM, bla GES, bla OXA-48, bla IMP, bla IMI, and bla VIM were screened with multiplexed PCR. All carbapenemase-positive isolates were identified taxonomically to species or genus level with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The nucleic acid extraction was successful for 399 isolates, of which 59 (14.8%) were found to carry carbapenemase genes. A total of 89.8% of the carbapenemase positive isolates (53 out of 59) were obtained from CHROMagarKPC plates and only 10.2% (six out of 59) were obtained from CHROMagar ESBL plates. Among the Carba-GNB isolates, 86.4% were bla GES (51 out of 59), 10.2% were bla KPC (six out of 59), and 3.4% were bla VIM (two out of 59). The most common carba-gene, bla GES, was carried by 10 different bacterial species, including Aeromonas spp., Enterobacter spp., and Kluyvera spp.; the bla KPC gene was carried by Escherichia coli, Klebsiella pneumoniae, and Kluyvera cryocescens; and the bla VIM gene was carried by Aeromonas hydrophila/caviae and Citrobacter amalonaticus. This study emphasizes that wastewater surveillance (WWS) can be an additional tool for monitoring antimicrobial resistance (AMR) at the population level.

Dataset Information

Comparative analysis of phosphoethanolamine transferases involved in polymyxin resistance across 10 clinically relevant Gram-negative bacteria.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets