التفاصيل البيبلوغرافية
العنوان: |
A proteomic perspective on the resistance response of Klebsiella pneumoniae to antimicrobial peptide PaDBS1R1. |
المؤلفون: |
Fleitas, Osmel, Fontes, Wagner, Souza, Camila M De, Costa, Mylena C Da, Cardoso, Marlon H, Castro, Mariana S, Sousa, Marcelo V, Ricart, Carlos A O, Ramada, Marcelo H S, Duque, Harry M, Porto, William F, Silva, Osmar N, Franco, Octávio L |
المصدر: |
Journal of Antimicrobial Chemotherapy (JAC); Jan2024, Vol. 79 Issue 1, p112-122, 11p |
مصطلحات موضوعية: |
ANTIMICROBIAL peptides, KLEBSIELLA pneumoniae, PROTEOMICS, BIOLOGICAL evolution, GENE ontology, PEPTIDE antibiotics |
مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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قاعدة البيانات: |
Complementary Index |