A subtractive proteomics approach for the identification of immunodominant Acinetobacter baumannii vaccine candidate proteins

Abstract

Background: Acinetobacter baumannii is one of the most life-threatening multidrug-resistant pathogens worldwide. Currently, 50%–70% of clinical isolates of A. baumannii are extensively drug-resistant, and available antibiotic options against A. baumannii infections are limited. There is still a need to discover specific de facto bacterial antigenic proteins that could be effective vaccine candidates in human infection. With the growth of research in recent years, several candidate molecules have been identified for vaccine development. So far, no public health authorities have approved vaccines against A. baumannii. Methods: This study aimed to identify immunodominant vaccine candidate proteins that can be immunoprecipitated specifically with patients’ IgGs, relying on the hypothesis that the infected person’s IgGs can capture immunodominant bacterial proteins. Herein, the outer-membrane and secreted proteins of sensitive and drug-resistant A. baumannii were captured using IgGs obtained from patient and healthy control sera and identified by Liquid Chromatography- Tandem Mass Spectrometry (LC-MS/MS) analysis. Results: Using the subtractive proteomic approach, we determined 34 unique proteins captured only in drug-resistant A. baumannii strain via patient sera. After extensively evaluating the predicted epitope regions, solubility, transverse membrane characteristics, and structural properties, we selected several notable vaccine candidates. Conclusion: We identified vaccine candidate proteins that triggered a de facto response of the human immune system against the antibiotic-resistant A. Frontiers in Immunology 01 frontiersin.org OPEN ACCESS EDITED BY Saeed Khalili, Shahid Rajaee Teacher Training University, Iran REVIEWED BY Abbas Yadegar, Shahid Beheshti University of Medical Sciences, Iran Prince Sharma, Panjab University, India Seung Il Kim, Korea Basic Science Institute (KBSI), South Korea *CORRESPONDENCE Servet Özcan ozcan@erciyes.edu.tr SPECIALTY SECTION This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology RECEIVED 23 July 2022 ACCEPTED 10 October 2022 PUBLISHED 10 November 2022 CITATION Acar MB, Ayaz-Güner S¸, Güner H, Dinc¸ G, Ulu Kılıc¸ A, Dog˘ anay M and Özcan S (2022) A subtractive proteomics approach for the identification of immunodominant Acinetobacter baumannii vaccine candidate proteins. Front. Immunol. 13:1001633. doi: 10.3389/fimmu.2022.1001633 COPYRIGHT © 2022 Acar, Ayaz-Güner, Güner, Dinc¸, Ulu Kılıc¸, Dog˘ anay and Özcan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Original Research PUBLISHED 10 November 2022 DOI 10.3389/fimmu.2022.1001633 baumannii. Precipitation of bacterial proteins via patient immunoglobulins was a novel approach to identifying the proteins that could trigger a response in the patient immune system.