Dataset Information

Insights of the metabolic adaptation to low concentrations of ertapenem of a carbapenem resistant Klebsiella pneumoniae strain

ABSTRACT: Klebsiella pneumoniae carrying antibiotic resistance against carbapenems are of great concern, due to the limited number of treatment options for infections caused by multiresistant bacteria. Novel antibiotics and treatment options are thus needed, and this need is exacerbated by the rapid and global spread of antibiotic resistances. In this study, we observe the global proteome changes of a K. pneumoniae strain (CCUG 70747) carrying carbapenem resistance genes under different concen-trations of ertapenem, a carbapenem antibiotic. Bottom-up tandem mass spectrometry (LC-MS/MS) was employed in combination with tandem mass tag (TMT) quantitative proteomics. Bioinformatics pipelines were used to observe changes in the GO terms and pathways associated with the differentially expressed proteins. The number of proteins detected with significant dif-ferential expression were 87 in the highest concentration applied and 61 in the lowest concentra-tion, all compared to the strain cultured without any antibiotics present. Several of these proteins, as well as the GO terms and pathways associated with the proteins, were linked to mechanisms of antibiotic resistance. However, this particular strain encodes potent β-lactamases, and thus, as expected, presented a reasonably modest impact in the global proteome upon exposure to the low concentrations of ertapenem applied.

INSTRUMENT(S):

ORGANISM(S): Klebsiella Pneumoniae

TISSUE(S): Cell Suspension Culture

SUBMITTER: Proteomics Core Facility

LAB HEAD: Roger Karlsson

PROVIDER: PXD061842 | Pride | 2025-10-06

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	3301_Set2_KP70747_Lumos_191206_23to32.msf	Msf
	3301_Set2_KP70747_Lumos_191206_23to32.pdResult	Other
	Lumos_191206_23.raw	Raw
	Lumos_191206_24.raw	Raw
	Lumos_191206_25.raw	Raw

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Publications

Insights into the Metabolic Adaptations of a Carbapenem-Resistant Klebsiella pneumoniae Strain on Exposure to Sublethal Concentrations of Ertapenem.

Jaén-Luchoro Daniel D Salvà-Serra Francisco F Piñeiro-Iglesias Beatriz B Marathe Nachiket N Moore Edward R B ERB Karlsson Roger R

International journal of molecular sciences 20250915 18

Klebsiella pneumoniae strains that are resistant to carbapenems are of great concern. Exposure to low concentrations of antibiotics may influence tolerance to antibiotics. Novel antibiotics and treatment options are thus needed, and this need is exacerbated by the rapid and global spread of antibiotic resistance. In this study, we determined the global proteome changes in a K. pneumoniae strain (CCUG 70747) carrying carbapenem resistance genes when exposed to low concentrations of ...[more]

PMID: 41009554

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Project description:Pseudomonas aeruginosa is a major opportunistic pathogen causing a wide range of infections and one of the most problematic bacteria regarding antibiotic resistance, with an increasing incidence of multidrug and extensively-drug resistant strains, including resistance to last resource antibiotics such as carbapenems. Resistances are often due to complex interplays of naturally and acquired resistance mechanisms which are enhanced by its remarkably large regulatory network. Thus, the use of non-targeted shotgun methodologies such as mass spectrometry-based proteomics is crucial to understand these interplays and to reveal possible strain and species-specific novel mechanisms of antibiotic resistance. The aim of this study was to determine the proteomic response of two carbapenem-resistant and extensively-drug-resistant P. aeruginosa strains to subminimal inhibitory concentrations (sub-MICs) of meropenem. The strains belonged to high-risk clones ST235 and ST395, one carrying a class 1 integron-encoded VIM-4 metallo-β-lactamase and one carrying no acquired antibiotic resistance genes. Each strain was cultivated with three different sub-MICs of meropenem, and a quantitative shotgun proteomic approach was applied, using tandem mass tag (TMT) isobaric labeling followed by nano-liquid chromatography tandem-mass spectrometry, to determine significantly up- or down-regulated proteins and enriched groups of proteins and pathways. Cultivation of both strains with ½ and ¼ of the MIC, resulted in hundreds of differentially regulated proteins, including several β-lactamases, transport-related proteins (including multiple porins and efflux pumps), proteins associated with peptidoglycan metabolism and cell wall organization and dozens of regulatory proteins. Remarkably, all components of the H1 type VI secretion system were up-regulated in one of the strains. Enrichment analyses revealed that multiple metabolic pathways were affected. Additionally, numerous proteins of unknown function were also differentially-regulated in each strain. In conclusion, high subminimal-inhibitory concentrations of meropenem cause massive changes in the proteomes of carbapenem-resistant P. aeruginosa strains, involving a wide range of common and strain-specific mechanisms and proteins, many still uncharacterized which might potentially play a role in the susceptibility of P. aeruginosa to meropenem.

Dataset Information

Insights of the metabolic adaptation to low concentrations of ertapenem of a carbapenem resistant Klebsiella pneumoniae strain

Dataset's files

Publications

Insights into the Metabolic Adaptations of a Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Strain on Exposure to Sublethal Concentrations of Ertapenem.

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Dataset Information

Insights of the metabolic adaptation to low concentrations of ertapenem of a carbapenem resistant Klebsiella pneumoniae strain

Dataset's files

Publications

Insights into the Metabolic Adaptations of a Carbapenem-Resistant &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; Strain on Exposure to Sublethal Concentrations of Ertapenem.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Insights into the Metabolic Adaptations of a Carbapenem-Resistant <i>Klebsiella pneumoniae</i> Strain on Exposure to Sublethal Concentrations of Ertapenem.