Cargando…
Integrated Genome-Wide Analysis of an Isogenic Pair of Pseudomonas aeruginosa Clinical Isolates with Differential Antimicrobial Resistance to Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Piperacillin/Tazobactam
Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the main causes of morbidity and mortality in hospitalized patients and the leading cause of nosocomial infections. We investigated, here, two MDR P. aeruginosa clinical isolates from a hospitalized patient with differential antimicrobial re...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037351/ https://www.ncbi.nlm.nih.gov/pubmed/32033143 http://dx.doi.org/10.3390/ijms21031026 |
_version_ | 1783500407594549248 |
---|---|
author | Huang, Weihua Hamouche, Joelle El Wang, Guiqing Smith, Melissa Yin, Changhong Dhand, Abhay Dimitrova, Nevenka Fallon, John T. |
author_facet | Huang, Weihua Hamouche, Joelle El Wang, Guiqing Smith, Melissa Yin, Changhong Dhand, Abhay Dimitrova, Nevenka Fallon, John T. |
author_sort | Huang, Weihua |
collection | PubMed |
description | Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the main causes of morbidity and mortality in hospitalized patients and the leading cause of nosocomial infections. We investigated, here, two MDR P. aeruginosa clinical isolates from a hospitalized patient with differential antimicrobial resistance to ceftazidime/avibactam (CZA), ceftolozane/tazobactam (C/T), and piperacillin/tazobactam (P/T). Their assembled complete genomes revealed they belonged to ST235, a widespread MDR clone; and were isogenic with only a single nucleotide variant, causing G183D mutation in AmpC β-lactamase, responsible for a phenotypic change from susceptible to resistant to CZA and C/T. Further epigenomic profiling uncovered two conserved DNA methylation motifs targeted by two distinct putative methyltransferase-containing restriction-modification systems, respectively; more intriguingly, there was a significant difference between the paired isolates in the pattern of genomic DNA methylation and modifications. Moreover, genome-wide gene expression profiling demonstrated the inheritable genomic methylation and modification induced 14 genes being differentially regulated, of which only toxR (downregulated), a regulatory transcription factor, had its promoter region differentially methylate and modified. Since highly expressed opdQ encodes an OprD porin family protein, therefore, we proposed an epigenetic regulation of opdQ expression pertinent to the phenotypic change of P. aeruginosa from resistant to susceptible to P/T. The disclosed epigenetic mechanism controlling phenotypic antimicrobial resistance deserves further experimental investigation. |
format | Online Article Text |
id | pubmed-7037351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70373512020-03-11 Integrated Genome-Wide Analysis of an Isogenic Pair of Pseudomonas aeruginosa Clinical Isolates with Differential Antimicrobial Resistance to Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Piperacillin/Tazobactam Huang, Weihua Hamouche, Joelle El Wang, Guiqing Smith, Melissa Yin, Changhong Dhand, Abhay Dimitrova, Nevenka Fallon, John T. Int J Mol Sci Article Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the main causes of morbidity and mortality in hospitalized patients and the leading cause of nosocomial infections. We investigated, here, two MDR P. aeruginosa clinical isolates from a hospitalized patient with differential antimicrobial resistance to ceftazidime/avibactam (CZA), ceftolozane/tazobactam (C/T), and piperacillin/tazobactam (P/T). Their assembled complete genomes revealed they belonged to ST235, a widespread MDR clone; and were isogenic with only a single nucleotide variant, causing G183D mutation in AmpC β-lactamase, responsible for a phenotypic change from susceptible to resistant to CZA and C/T. Further epigenomic profiling uncovered two conserved DNA methylation motifs targeted by two distinct putative methyltransferase-containing restriction-modification systems, respectively; more intriguingly, there was a significant difference between the paired isolates in the pattern of genomic DNA methylation and modifications. Moreover, genome-wide gene expression profiling demonstrated the inheritable genomic methylation and modification induced 14 genes being differentially regulated, of which only toxR (downregulated), a regulatory transcription factor, had its promoter region differentially methylate and modified. Since highly expressed opdQ encodes an OprD porin family protein, therefore, we proposed an epigenetic regulation of opdQ expression pertinent to the phenotypic change of P. aeruginosa from resistant to susceptible to P/T. The disclosed epigenetic mechanism controlling phenotypic antimicrobial resistance deserves further experimental investigation. MDPI 2020-02-04 /pmc/articles/PMC7037351/ /pubmed/32033143 http://dx.doi.org/10.3390/ijms21031026 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Huang, Weihua Hamouche, Joelle El Wang, Guiqing Smith, Melissa Yin, Changhong Dhand, Abhay Dimitrova, Nevenka Fallon, John T. Integrated Genome-Wide Analysis of an Isogenic Pair of Pseudomonas aeruginosa Clinical Isolates with Differential Antimicrobial Resistance to Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Piperacillin/Tazobactam |
title | Integrated Genome-Wide Analysis of an Isogenic Pair of Pseudomonas aeruginosa Clinical Isolates with Differential Antimicrobial Resistance to Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Piperacillin/Tazobactam |
title_full | Integrated Genome-Wide Analysis of an Isogenic Pair of Pseudomonas aeruginosa Clinical Isolates with Differential Antimicrobial Resistance to Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Piperacillin/Tazobactam |
title_fullStr | Integrated Genome-Wide Analysis of an Isogenic Pair of Pseudomonas aeruginosa Clinical Isolates with Differential Antimicrobial Resistance to Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Piperacillin/Tazobactam |
title_full_unstemmed | Integrated Genome-Wide Analysis of an Isogenic Pair of Pseudomonas aeruginosa Clinical Isolates with Differential Antimicrobial Resistance to Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Piperacillin/Tazobactam |
title_short | Integrated Genome-Wide Analysis of an Isogenic Pair of Pseudomonas aeruginosa Clinical Isolates with Differential Antimicrobial Resistance to Ceftolozane/Tazobactam, Ceftazidime/Avibactam, and Piperacillin/Tazobactam |
title_sort | integrated genome-wide analysis of an isogenic pair of pseudomonas aeruginosa clinical isolates with differential antimicrobial resistance to ceftolozane/tazobactam, ceftazidime/avibactam, and piperacillin/tazobactam |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037351/ https://www.ncbi.nlm.nih.gov/pubmed/32033143 http://dx.doi.org/10.3390/ijms21031026 |
work_keys_str_mv | AT huangweihua integratedgenomewideanalysisofanisogenicpairofpseudomonasaeruginosaclinicalisolateswithdifferentialantimicrobialresistancetoceftolozanetazobactamceftazidimeavibactamandpiperacillintazobactam AT hamouchejoelleel integratedgenomewideanalysisofanisogenicpairofpseudomonasaeruginosaclinicalisolateswithdifferentialantimicrobialresistancetoceftolozanetazobactamceftazidimeavibactamandpiperacillintazobactam AT wangguiqing integratedgenomewideanalysisofanisogenicpairofpseudomonasaeruginosaclinicalisolateswithdifferentialantimicrobialresistancetoceftolozanetazobactamceftazidimeavibactamandpiperacillintazobactam AT smithmelissa integratedgenomewideanalysisofanisogenicpairofpseudomonasaeruginosaclinicalisolateswithdifferentialantimicrobialresistancetoceftolozanetazobactamceftazidimeavibactamandpiperacillintazobactam AT yinchanghong integratedgenomewideanalysisofanisogenicpairofpseudomonasaeruginosaclinicalisolateswithdifferentialantimicrobialresistancetoceftolozanetazobactamceftazidimeavibactamandpiperacillintazobactam AT dhandabhay integratedgenomewideanalysisofanisogenicpairofpseudomonasaeruginosaclinicalisolateswithdifferentialantimicrobialresistancetoceftolozanetazobactamceftazidimeavibactamandpiperacillintazobactam AT dimitrovanevenka integratedgenomewideanalysisofanisogenicpairofpseudomonasaeruginosaclinicalisolateswithdifferentialantimicrobialresistancetoceftolozanetazobactamceftazidimeavibactamandpiperacillintazobactam AT fallonjohnt integratedgenomewideanalysisofanisogenicpairofpseudomonasaeruginosaclinicalisolateswithdifferentialantimicrobialresistancetoceftolozanetazobactamceftazidimeavibactamandpiperacillintazobactam |