A proteomic perspective on the resistance response of <i>Klebsiella pneumoniae</i> to antimicrobial peptide PaDBS1R1-Reference-Cited by-同舟云学术

A proteomic perspective on the resistance response of Klebsiella pneumoniae to antimicrobial peptide PaDBS1R1

Published:2023-11-15 Issue:1 Volume:79 Page:112-122
ISSN:0305-7453
Container-title:Journal of Antimicrobial Chemotherapy
language:en
Short-container-title:

Author:

Fleitas Osmel¹²,Fontes Wagner¹³,De Souza Camila M²⁴,Da Costa Mylena C²,Cardoso Marlon H²⁵⁶,Castro Mariana S¹³,Sousa Marcelo V¹³,Ricart Carlos A O¹³,Ramada Marcelo H S⁴⁷,Duque Harry M²,Porto William F²,Silva Osmar N⁸,Franco Octávio L¹²⁴⁵^ORCID

Affiliation:

1. Programa de Pós-Graduação em Patologia Molecular, Universidade de Brasília , Brasília , Brazil

2. Centro de Análises Proteômicas e Bioquímicas, Universidade Católica de Brasília , Brasília , Brazil

3. Laboratório de Bioquímica e Química de Proteínas, Universidade de Brasília , Brasília , Brazil

4. Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília , Brasília , Brazil

5. S-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom Bosco , Campo Grande , Brazil

6. Instituto de Biociências (INBIO), Universidade Federal de Mato Grosso do Sul, Cidade Universitária , 79070900, Campo Grande, Mato Grosso do Sul , Brazil

7. Programa de Pós-Graduação em Gerontologia, Universidade Católica de Brasília , Brasília , Brazil

8. Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Evangélica de Anapólis, University City , 75083-515 Anápolis-GO , Brazil

Abstract

Abstract Background The synthetic antimicrobial peptide, PaDBS1R1, has been reported as a powerful anti-Klebsiella pneumoniae antimicrobial. However, there is only scarce knowledge about whether K. pneumoniae could develop resistance against PaDBS1R1 and which resistance mechanisms could be involved. Objectives Identify via label-free shotgun proteomics the K. pneumoniae resistance mechanisms developed against PaDBS1R1. Methods An adaptive laboratory evolution experiment was performed to obtain a PaDBS1R1-resistant K. pneumoniae lineage. Antimicrobial susceptibility was determined through microdilution assay. Modifications in protein abundances between the resistant and sensitive lineages were measured via label-free quantitative shotgun proteomics. Enriched Gene Ontology terms and KEGG pathways were identified through over-representation analysis. Data are available via ProteomeXchange with identifier PXD033020. Results K. pneumoniae ATCC 13883 parental strain challenged with increased subinhibitory PaDBS1R1 concentrations allowed the PaDBS1R1-resistant K. pneumoniae lineage to emerge. Proteome comparisons between PaDBS1R1-resistant K. pneumoniae and PaDBS1R1-sensitive K. pneumoniae under PaDBS1R1-induced stress conditions enabled the identification and quantification of 1702 proteins, out of which 201 were differentially abundant proteins (DAPs). The profiled DAPs comprised 103 up-regulated proteins (adjusted P value < 0.05, fold change ≥ 2) and 98 down-regulated proteins (adjusted P value < 0.05, fold change ≤ 0.5). The enrichment analysis suggests that PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery could be relevant resistance mechanisms against PaDBS1R1. Conclusions Based on experimental evolution and a label-free quantitative shotgun proteomic approach, we showed that K. pneumoniae developed resistance against PaDBS1R1, whereas PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery appear to be relevant resistance mechanisms against PaDBS1R1.

Funder

CAPES

CNPq

FAPDF

FUNDECT

FINEP

UnB

UCB

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)