Dataset Information

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii.

ABSTRACT: Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent public health threat, according to the CDC. This pathogen has few treatment options and causes severe nosocomial infections with >50% fatality rate. Although previous studies have examined the proteome of CRAb, there have been no focused analyses of dynamic changes to β-lactamase expression that may occur due to drug exposure. Here, we present our initial proteomic study of variation in β-lactamase expression that occurs in CRAb with different β-lactam antibiotics. Briefly, drug resistance to Ab (ATCC 19606) was induced by the administration of various classes of β-lactam antibiotics, and the cell-free supernatant was isolated, concentrated, separated by SDS-PAGE, digested with trypsin, and identified by label-free LC-MS-based quantitative proteomics. Thirteen proteins were identified and evaluated using a 1789 sequence database of Ab β-lactamases from UniProt, the majority of which were Class C β-lactamases (≥80%). Importantly, different antibiotics, even those of the same class (e.g. penicillin and amoxicillin), induced non-equivalent responses comprising various isoforms of Class C and D serine-β-lactamases, resulting in unique resistomes. These results open the door to a new approach of analyzing and studying the problem of multi-drug resistance in bacteria that rely strongly on β-lactamase expression.

INSTRUMENT(S): timsTOF Pro 2

ORGANISM(S): Acinetobacter Baumannii A424 Bacteria

DISEASE(S): Bacterial Infectious Disease

SUBMITTER: Belinda Willard

LAB HEAD: Woo Shik Shin

PROVIDER: PXD042336 | Pride | 2023-07-20

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	A.baumannii_beta-lactamase_sequence_2639_library_fasta.fasta	Fasta
	sdrf.tsv	Tabular
	tims_21nov0901_Slot1-6_1_313.d.zip	Other
	tims_21nov0901_Slot1-6_1_313.mzML	Mzml
	tims_21nov0901_Slot1-6_1_313.pepXML	Pepxml

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Publications

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii.

Hillyer Trae T Benin Bogdan M BM Sun Chuanqi C Aguirre Noah N Willard Belinda B Sham Yuk Yin YY Shin Woo Shik WS

Scientific reports 20230606 1

Carbapenem-resistant Acinetobacter baumannii (CRAb) is an urgent public health threat, according to the CDC. This pathogen has few treatment options and causes severe nosocomial infections with > 50% fatality rate. Although previous studies have examined the proteome of CRAb, there have been no focused analyses of dynamic changes to β-lactamase expression that may occur due to drug exposure. Here, we present our initial proteomic study of variation in β-lactamase expression that occurs in CRAb w ...[more]

PMID: 37280269

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Project description:Background: Antimicrobial resistance is generally studied using a combination of growth inhibition measurements, sometimes in combination with DNA detection methods. However, the actual proteins that cause resistance such as enzymes, efflux pumps and a lack of porins cannot be detected by these methods. Improvements in liquid chromatography (LC) and mass spectrometry (MS) enabled easier and more comprehensive proteome analysis. In the current study, these three methods are combined into a multi-omics approach to analyze resistance against frequently used antibiotics within the beta-lactam, aminoglycoside and fluoroquinolone group in E. coli and K. pneumoniae. Objectives: We aimed to analyze which currently known antimicrobial resistance genes are detected at the protein level using liquid chromatography-mass spectrometry (LC-MS/MS) and to assess whether these could explain beta-lactam, aminoglycoside, and fluoroquinolone resistance in the studied isolates. Furthermore, we aimed to identify significant protein to resistance correlations which have not yet been described and to correlate the abundance of different porins to resistance. Methods: Whole genome sequencing, high-resolution LC-MS/MS and antimicrobial susceptibility testing by broth microdilution were performed for 187 clinical E. coli and K. pneumoniae isolates. Resistance genes and proteins were identified using the Comprehensive Antibiotic Resistance Database (CARD). All proteins were annotated using the NCBI RefSeq database and Prokka. Results & Conclusion: Proteins of small spectrum beta-lactamases, extended spectrum beta-lactamases, AmpC beta-lactamases, carbapenemases, and proteins of 16S ribosomal RNA methyltransferases and aminoglycoside acetyltransferases can be detected in E. coli and K. pneumoniae by LC-MS/MS. The detected mechanisms could explain phenotypic resistance in most of the studied isolates. Differences in the abundance and the primary structure of other proteins such as porins also correlated with resistance. LC-MS/MS is a different and complementary method which can be used to characterize antimicrobial resistance in detail as not only the primary resistance causing mechanisms are detected, but also secondary enhancing resistance mechanisms.

Dataset Information

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii.

Dataset's files

Publications

A novel strategy to characterize the pattern of β-lactam antibiotic-induced drug resistance in Acinetobacter baumannii.

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