Unbiased antimicrobial resistance detection from clinical bacterial isolates using proteomics

Blumenscheit, Christian; Pfeifer, Yvonne; Werner, Guido; John, Charlyn; Schneider, Andy; Doellinger, Joerg

doi:10.1101/2020.11.17.386540

Cited by 2 publications

(1 citation statement)

References 57 publications

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“…Statistically significant differentially abundant (SSDA) proteins arising from pairwise t-tests were determined between the groups and included 95 for ampicillin vs control, 145 for cefotaxime vs control, 89 for imipenem vs control and 208 ciprofloxacin vs control (Supplemental dataset [3][4][5][6]. The 20 most differentially abundant proteins between each group are highlighted and labelled on the volcano plots (Fig.…”

Section: Resultsmentioning

confidence: 99%

Global protein responses of multi-drug resistant plasmid containing Escherichia coli to ampicillin, cefotaxime, imipenem and ciprofloxacin

Margalit

Carolan

Walsh

2021

Preprint

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Antimicrobial resistance (AMR) and multidrug resistance (MDR) in pathogenic bacteria are frequently mediated by plasmids. However, plasmids do not exist in isolation but rather require the bacterial host interaction in order to produce the AMR phenotype. This study aimed to utilise mass spectrometry based proteomics to reveal the plasmid and chromosomally derived protein profile of Escherichia coli under antimicrobial stress. This was achieved by comparing the proteomes of E. coli containing the MDR pEK499 plasmid, under ampicillin, cefotaxime, imipenem or ciprofloxacin stress with the proteomes of these bacteria grown in the absence of antimicrobial. Our analysis identified statistically significant differentially abundant proteins common to groups exposed to the beta-lactam antimicrobials but not ciprofloxacin, indicating a betalactam stress response to exposure from this class of drugs, irrespective of betalactam resistance or susceptibility. These include ecotin and free methionine R sulfoxide reductase. These data also identified distinct differences in the cellular response to each betalactam. Data arising from comparisons of the proteomes of ciprofloxacin treated E. coli and controls detected an increase in the relative abundance of proteins associated with ribosomes, translation, the TCA cycle and several proteins associated with detoxification and a decrease in the relative abundances of proteins associated with stress response, including oxidative stress. We identified changes in proteins associated with persister formation in the presence of ciprofloxacin but not the betalactams. The plasmid proteome differed across each treatment and did not follow the pattern of antimicrobial AMR protein associations. For example, a relative increase in the amount of blaCTXM15 in the presence of cefotaxime and ciprofloxacin but not the other betalactams, suggesting regulation of the blaCTXM15 protein production. The proteomic data from the this study provided novel insights into the proteins produced from the chromosome and plasmid under different antimicrobial stresses. These data also identified novel proteins not previously associated with AMR or antimicrobials responses in pathogens, which may well represent potential targets of AMR inhibition.

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Section: Resultsmentioning

confidence: 99%

Global protein responses of multi-drug resistant plasmid containing Escherichia coli to ampicillin, cefotaxime, imipenem and ciprofloxacin

Margalit

Carolan

Walsh

2021

Preprint

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Software Solutions for Indication and Identification of Pathogenic Microoranisms Using Time-of-Flight Mass Spectrometry

Ульшина¹,

Kovalev²,

Кузнецова³

et al. 2021

Problemy Osobo Opasnykh Infektsii

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The effectiveness of differentiation of bacterial pathogens using MALDI-TOF mass spectrometry depends on the quality of sample preparation, compliance with mass spectrometric analysis parameters and statistical approaches used, implemented by various modern software tools. The review provides a brief description of the most known software used in the processing and bioinformation analysis of time-of-flight mass spectrometry data. A list of computer platforms, programs and environments, both commercial and publicly available, is presented. The results of indication and identification of pathogens of particularly dangerous and natural-focal infections by MALDI-TOF mass spectrometry using publicly available software – programming language R, Mass-Up, MicrobeMS, licensed – MatLab, ClinProTools, as well as free web applications, including, Speclust, Ribopeaksare provided. The data on usage of such well-known platforms as MALDI BioTyper, SARAMIS Vitek-MS and Andromas (Andromas SAS, France) for inter- and intra-specific differentiation of closely related species are presented. Results of identification and differentiation of microorganisms applying MALDI-TOF mass spectrometry based on detection of specific proteins for cross-comparison – biomarkers – are given. The analysis shows that the programming language R environment is one of the publicly available universal platforms with an optimal combination of algorithms for processing and interpreting of a large array of mass spectrometric data.

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Unbiased antimicrobial resistance detection from clinical bacterial isolates using proteomics

Cited by 2 publications

References 57 publications

Global protein responses of multi-drug resistant plasmid containing Escherichia coli to ampicillin, cefotaxime, imipenem and ciprofloxacin

Global protein responses of multi-drug resistant plasmid containing Escherichia coli to ampicillin, cefotaxime, imipenem and ciprofloxacin

Software Solutions for Indication and Identification of Pathogenic Microoranisms Using Time-of-Flight Mass Spectrometry

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