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

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Abstract

Background

Outer 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.

Methods

Purified 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.

Results

OMV 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.

Conclusion

In vitro stress such as antibiotic treatment can modulate proteome components in A. baumannii OMVs and thereby influence pathogenicity.

Electronic supplementary material

The online version of this article (10.1186/s12014-018-9204-2) contains supplementary material, which is available to authorized users.

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Most cited references 36

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The Acinetobacter baumannii 19606 OmpA protein plays a role in biofilm formation on abiotic surfaces and in the interaction of this pathogen with eukaryotic cells.

Jennifer Gaddy, Andrew P. Tomaras, Luis A. Actis (2009)

The ability of Acinetobacter baumannii to adhere to and persist on surfaces as biofilms could be central to its pathogenicity. The production of pili and a biofilm-associated protein and the expression of antibiotic resistance are needed for robust biofilm formation on abiotic and biotic surfaces. This multistep process also depends on the expression of transcriptional regulatory functions, some of which could sense nutrients available to cells. This report extends previous observations by showing that although outer membrane protein A (OmpA) of A. baumannii 19606 plays a partial role in the development of robust biofilms on plastic, it is essential for bacterial attachment to Candida albicans filaments and A549 human alveolar epithelial cells. In contrast to abiotic surfaces, the interaction with biotic surfaces is independent of the CsuA/BABCDE-mediated pili. The interaction of A. baumannii 19606 with fungal and epithelial cells also results in their apoptotic death, a response that depends on the direct contact of bacteria with these two types of eukaryotic cells. Furthermore, the bacterial adhesion phenotype correlates with the ability of bacteria to invade A549 epithelial cells. Interestingly, the killing activity of cell-free culture supernatants proved to be protease and temperature sensitive, suggesting that its cytotoxic activity is due to secreted proteins, some of which are different from OmpA.

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Virulence factors are released from Pseudomonas aeruginosa in association with membrane vesicles during normal growth and exposure to gentamicin: a novel mechanism of enzyme secretion.

J Kadurugamuwa, T. J. Beveridge (1995)

Pseudomonas aeruginosa blebs-off membrane vesicles (MVs) into culture medium during normal growth. Release of these vesicles increased approximately threefold after exposure of the organism to four times the MIC of gentamicin. Natural and gentamicin-induced membrane vesicles (n-MVs and g-MVs and g-MVs, respectively) were isolated by filtration and differential centrifugation, and several of their biological activities were characterized. Electron microscopy of both n-MVs and g-MVs revealed that they were spherical bilayer MVs with a diameter of 50 to 150 nm. Immunoelectron microscopy and Western blot (immunoblot) analysis of the vesicles demonstrated the presence of B-band lipopolysaccharide (LPS), with a slightly higher proportion of B-band LPS in g-MVs than in n-MVs. A-band LPS was occasionally detected in g-MVs but not in n-MVs. In addition to LPS, several enzymes, such as phospholipase C, protease, hemolysin, and alkaline phosphatase, which are known to contribute to the pathogenicity of Pseudomonas infections were found to be present in both vesicle types. Both types of vesicles contained DNA, with a significantly higher content in g-MVs. These vesicles could thus play an important role in genetic transformation and disease by serving as a transport vehicle for DNA and virulence factors and are presumably involved in septic shock.

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Acinetobacter baumannii Secretes Cytotoxic Outer Membrane Protein A via Outer Membrane Vesicles

Jong Jin, Sang-Oh Kwon, Dong Moon … (2011)

Acinetobacter baumannii is an important nosocomial pathogen that causes a high morbidity and mortality rate in infected patients, but pathogenic mechanisms of this microorganism regarding the secretion and delivery of virulence factors to host cells have not been characterized. Gram-negative bacteria naturally secrete outer membrane vesicles (OMVs) that play a role in the delivery of virulence factors to host cells. A. baumannii has been shown to secrete OMVs when cultured in vitro, but the role of OMVs in A. baumannii pathogenesis is not well elucidated. In the present study, we evaluated the secretion and delivery of virulence factors of A. baumannii to host cells via the OMVs and assessed the cytotoxic activity of outer membrane protein A (AbOmpA) packaged in the OMVs. A. baumannii ATCC 19606T secreted OMVs during in vivo infection as well as in vitro cultures. Potential virulence factors, including AbOmpA and tissue-degrading enzymes, were associated with A. baumannii OMVs. A. baumannii OMVs interacted with lipid rafts in the plasma membranes and then delivered virulence factors to host cells. The OMVs from A. baumannii ATCC 19606T induced apoptosis of host cells, whereas this effect was not detected in the OMVs from the ΔompA mutant, thereby reflecting AbOmpA-dependent host cell death. The N-terminal region of AbOmpA22-170 was responsible for host cell death. In conclusion, the OMV-mediated delivery of virulence factors to host cells may well contribute to pathogenesis during A. baumannii infection.

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Author and article information

Contributors

Gun-Hwa Kim: genekgh@kbsi.re.kr

Seung Il Kim: ksi@kbsi.re.kr

Journal

Journal ID (nlm-ta): Clin Proteomics

Journal ID (iso-abbrev): Clin Proteomics

Title: Clinical Proteomics

Publisher: BioMed Central (London )

ISSN (Print): 1542-6416

ISSN (Electronic): 1559-0275

Publication date (Electronic): 31 August 2018

Publication date PMC-release: 31 August 2018

Publication date Collection: 2018

Volume: 15

Electronic Location Identifier: 28

Affiliations

[1 ]ISNI 0000 0000 9149 5707, GRID grid.410885.0, Drug and Disease Target Team, , Korea Basic Science Institute, ; Cheongju, 28119 Republic of Korea

[2 ]ISNI 0000 0001 2296 8192, GRID grid.29869.3c, Center for Convergent Research of Emerging Virus Infection, , Korea Research Institute of Chemical Technology, ; Daejeon, 34114 Republic of Korea

[3 ]ISNI 0000 0004 1791 8264, GRID grid.412786.e, Bio-Analysis Science, , University of Science and Technology, ; Daejeon, 34113 Republic of Korea

[4 ]KBNP Technology Institute, KBNP, INC., Anyang, 14059 Republic of Korea

[5 ]ISNI 0000 0001 0661 1556, GRID grid.258803.4, Department of Microbiology, , Kyungpook National University School of Medicine, ; Daegu, 41944 Republic of Korea

[6 ]ISNI 0000 0000 9149 5707, GRID grid.410885.0, Protein Structure Team, , Korea Basic Science Institute, ; Cheongju, 28119 Republic of Korea

Article

Publisher ID: 9204

DOI: 10.1186/s12014-018-9204-2

PMC ID: 6118003

PubMed ID: 29321721

SO-VID: e343a638-d5ac-477a-b424-0c21b32ab4af

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 24 April 2018

Date accepted : 16 August 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100003710, Korea Health Industry Development Institute;

Award ID: HI14C2726

Award Recipient : Gun-Hwa Kim

Funded by: FundRef http://dx.doi.org/10.13039/501100008783, National Research Council of Science and Technology;

Award ID: CRC-16-01-KRICT

Award Recipient : Seung Il Kim

Funded by: FundRef http://dx.doi.org/10.13039/501100003716, Korea Basic Science Institute;

Award ID: C38932

Award Recipient : Gun-Hwa Kim

Custom metadata

ScienceOpen disciplines: Molecular medicine

Keywords: proteomics,acinetobacter baumannii,outer membrane vesicles,modulation by antibiotic treatment

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ScienceOpen disciplines: Molecular medicine

Keywords: proteomics, acinetobacter baumannii, outer membrane vesicles, modulation by antibiotic treatment

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

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Abstract

Background

Methods

Results

Conclusion

Electronic supplementary material

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Bacterial extracellular vesicles

Most cited references 36

The Acinetobacter baumannii 19606 OmpA protein plays a role in biofilm formation on abiotic surfaces and in the interaction of this pathogen with eukaryotic cells.

Virulence factors are released from Pseudomonas aeruginosa in association with membrane vesicles during normal growth and exposure to gentamicin: a novel mechanism of enzyme secretion.

Acinetobacter baumannii Secretes Cytotoxic Outer Membrane Protein A via Outer Membrane Vesicles

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Cited by 37

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