Proteogenomic characterization of antimicrobial resistance in extensively drug-resistant Acinetobacter baumannii DU202

Lee, Sangyeop; Yun, Sung Ho; Lee, Yeol Gyun; Choi, Chang Soo; Leem, Sun‐Hee; Park, Edmond Changkyun; Kim, Gun-Hwa; Lee, Je Chul; Kim, Kyung Sik

doi:10.1093/jac/dku008

Cited by 19 publications

(13 citation statements)

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“…We recently reported the complete genome of A. baumannii DU202 [16], and here we used this resource to perform proteogenomic analysis of protein components of OMVs following antibiotic treatment. Bacterial OMVs play important role as potent bacterial virulence factors [17] and a high incidence of resistance to imipenem has been reported for clinical A. baumannii strains in hospitals [18, 19].…”

Section: Introductionmentioning

confidence: 99%

Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202

et al. 2018

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BackgroundOuter membrane vesicles (OMVs) of Acinetobacter baumannii are cytotoxic and elicit a potent innate immune response. OMVs were first identified in A. baumannii DU202, an extensively drug-resistant clinical strain. Herein, we investigated protein components of A. baumannii DU202 OMVs following antibiotic treatment by proteogenomic analysis.MethodsPurified OMVs from A. baumannii DU202 grown in different antibiotic culture conditions were screened for pathogenic and immunogenic effects, and subjected to quantitative proteomic analysis by one-dimensional electrophoresis and liquid chromatography combined with tandem mass spectrometry (1DE-LC-MS/MS). Protein components modulated by imipenem were identified and discussed.ResultsOMV secretion was increased > twofold following imipenem treatment, and cytotoxicity toward A549 human lung carcinoma cells was elevated. A total of 277 proteins were identified as components of OMVs by imipenem treatment, among which β-lactamase OXA-23, various proteases, outer membrane proteins, β-barrel assembly machine proteins, peptidyl-prolyl cis–trans isomerases and inherent prophage head subunit proteins were significantly upregulated.ConclusionIn vitro stress such as antibiotic treatment can modulate proteome components in A. baumannii OMVs and thereby influence pathogenicity.Electronic supplementary materialThe online version of this article (10.1186/s12014-018-9204-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202

et al. 2018

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“…Quantitative mass spectrometry (MS) appears particularly attractive to achieve this goal (14). MS technologies are increasingly used to characterize A. baumannii at the protein level using both untargeted (4, [15][16] or targeted approaches (17). Untargeted MS has been extensively used in proteomics study for a long time since it allows stochastic identification of hundreds to thousands of proteins with a coarse quantitation.…”

Section: Introductionmentioning

confidence: 99%

Deciphering Multifactorial Resistance Phenotypes in Acinetobacter baumannii by Genomics and Targeted Label-free Proteomics

Cecchini

Yoon

Charretier

et al. 2018

Molecular & Cellular Proteomics

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4 SummaryResistance to β-lactams in Acinetobacter baumannii involves various mechanisms. To decipher them, whole genome sequencing (WGS) and real-time quantitative polymerase chain reaction (RT-qPCR) were complemented by mass spectrometry (MS) in selected reaction monitoring mode (SRM) in 39 clinical isolates. The targeted label-free proteomic approach enabled, in one hour and using a single method, the quantitative detection of 16 proteins associated with antibiotic resistance: eight acquired β-lactamases (i.e. GES, NDM-1, OXA-23, OXA-24, OXA-58, PER, TEM-1 and VEB), two resident β-lactamases (i.e. ADC and OXA-51-like) and six components of the two major efflux systems (i.e. AdeABC and AdeIJK). Results were normalized using "bacterial quantotypic peptides", i.e. peptide markers of the bacterial quantity, to obtain precise protein quantitation (on average 8.93% coefficient of variation for three biological replicates). This allowed to correlate the levels of resistance to β-lactam with those of the production of acquired as well as resident β-lactamases or of efflux systems. SRM detected enhanced ADC or OXA-51-like production and absence or increased efflux pump production.Precise protein quantitation was particularly valuable to detect resistance mechanisms mediated by regulated genes or by overexpression of chromosomal genes. Combination of WGS and MS, two orthogonal and complementary techniques, allows thereby interpretation of the resistance phenotypes at the molecular level.

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“…This observation could have implications for surface attachment, the initial stages of biofilm formation and the development of a resistant phenotype. In a similar manner, Lee et al (2014) identified individual β-lactamases in different cellular fractions of a MDR A. baumannii strain. Interestingly, two of the β-lactamases increased in response to imipenem, but one decreased in response to tetracycline.…”

Section: Thinking Inside the Proteome: Using High-resolution Ms To Exmentioning

confidence: 77%

“…databases containing the products of all possible six-frame translations of the genome). This area of proteomics, called proteogenomics, was used by Lee et al (2014) to characterize novel antibiotic resistance genes in an extensively drug resistant (XDR) clinical isolate of Acinetobacter baumannii (DU202) in response to antibiotic challenge. Their previous analysis of the MS data, which used a database generated from an A. baumannii reference strain, resulted in large number of the identified proteins being classified as 'hypothetical/putative' proteins.…”

Section: The Current State Of Bacterial Proteomics: Technologies and mentioning

confidence: 99%

“…The DU202-specific database identified 271 additional membrane-associated proteins and 26 additional cytoplasmic proteins. This study highlighted the different patterns of β-lactamase induction in response to various culture conditions (LB, tetracycline or imipenen) (Lee et al 2014). Others have also used the custom database approach to reduced processing burden when multiple strains are being examined.…”

Section: The Current State Of Bacterial Proteomics: Technologies and mentioning

confidence: 99%

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Survival proteomes: the emerging proteotype of antimicrobial resistance

Park

Krieger

Khursigara

2016

FEMS Microbiology Reviews

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Antimicrobial resistance is one of the greatest challenges in modern medicine. Infectious diseases that have historically been eliminated with routine antibiotic therapy are now re-emerging as life threatening illnesses. A better understanding of the specific mechanisms that contribute to resistance are required to optimize the treatment of infectious microorganisms and limit the survival of recalcitrant populations. This challenging area of research is made more problematic by the observation that multiple, overlapping, and/or compensatory resistance mechanism are often present within a single bacterial species. High-resolution proteomics has emerged as an effective tool to study antimicrobial resistance as it allows for the quantitative investigation of multiple systems concurrently. Furthermore, the ability to examine extracellular mechanisms of resistance and important post-translational modifications make this research tool well suited for the challenge. This review discusses how proteomics has contributed to the understanding of antimicrobial resistance and focuses on advances afforded by the more recent development of technologies that produce quantitative high-resolution proteomic information. We discuss current strategies for studying resistance, including comparative analysis of resistant and susceptible strains and protein-based responses to antimicrobial challenge. Lastly, we suggest specific experimental approaches aimed at advancing our understanding of protein-based resistance mechanisms and maximizing therapeutic outcomes in the future.

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Proteogenomic characterization of antimicrobial resistance in extensively drug-resistant Acinetobacter baumannii DU202

Abstract: Combining genomic and proteomic methods provided comprehensive information about the unique antibiotic resistance responses of A. baumannii DU202.

Cited by 19 publications

References 45 publications

Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202

Antibiotic treatment modulates protein components of cytotoxic outer membrane vesicles of multidrug-resistant clinical strain, Acinetobacter baumannii DU202

Deciphering Multifactorial Resistance Phenotypes in Acinetobacter baumannii by Genomics and Targeted Label-free Proteomics

Survival proteomes: the emerging proteotype of antimicrobial resistance

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