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Delineating the Plausible Molecular Vaccine Candidates and Drug Targets of Multidrug-Resistant Acinetobacter baumannii

Nosocomial infections have become alarming with the increase of multidrug-resistant bacterial strains of Acinetobacter baumannii. Being the causative agent in ~80% of the cases, these pathogenic gram-negative species could be deadly for hospitalized patients, especially in intensive care units utili...

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Autores principales: Mujawar, Shama, Mishra, Rohit, Pawar, Shrikant, Gatherer, Derek, Lahiri, Chandrajit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596342/
https://www.ncbi.nlm.nih.gov/pubmed/31281799
http://dx.doi.org/10.3389/fcimb.2019.00203
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author Mujawar, Shama
Mishra, Rohit
Pawar, Shrikant
Gatherer, Derek
Lahiri, Chandrajit
author_facet Mujawar, Shama
Mishra, Rohit
Pawar, Shrikant
Gatherer, Derek
Lahiri, Chandrajit
author_sort Mujawar, Shama
collection PubMed
description Nosocomial infections have become alarming with the increase of multidrug-resistant bacterial strains of Acinetobacter baumannii. Being the causative agent in ~80% of the cases, these pathogenic gram-negative species could be deadly for hospitalized patients, especially in intensive care units utilizing ventilators, urinary catheters, and nasogastric tubes. Primarily infecting an immuno-compromised system, they are resistant to most antibiotics and are the root cause of various types of opportunistic infections including but not limited to septicemia, endocarditis, meningitis, pneumonia, skin, and wound sepsis and even urinary tract infections. Conventional experimental methods including typing, computational methods encompassing comparative genomics, and combined methods of reverse vaccinology and proteomics had been proposed to differentiate and develop vaccines and/or drugs for several outbreak strains. However, identifying proteins suitable enough to be posed as drug targets and/or molecular vaccines against the multidrug-resistant pathogenic bacterial strains has probably remained an open issue to address. In these cases of novel protein identification, the targets either are uncharacterized or have been unable to confer the most coveted protection either in the form of molecular vaccine candidates or as drug targets. Here, we report a strategic approach with the 3,766 proteins from the whole genome of A. baumannii ATCC19606 (AB) to rationally identify plausible candidates and propose them as future molecular vaccine candidates and/or drug targets. Essentially, we started with mapping the vaccine candidates (VaC) and virulence factors (ViF) of A. baumannii strain AYE onto strain ATCC19606 to identify them in the latter. We move on to build small networks of VaC and ViF to conceptualize their position in the network space of the whole genomic protein interactome (GPIN) and rationalize their candidature for drugs and/or molecular vaccines. To this end, we propose new sets of known proteins unearthed from interactome built using key factors, KeF, potent enough to compete with VaC and ViF. Our method is the first of its kind to propose, albeit theoretically, a rational approach to identify crucial proteins and pose them for candidates of vaccines and/or drugs effective enough to combat the deadly pathogenic threats of A. baumannii.
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spelling pubmed-65963422019-07-05 Delineating the Plausible Molecular Vaccine Candidates and Drug Targets of Multidrug-Resistant Acinetobacter baumannii Mujawar, Shama Mishra, Rohit Pawar, Shrikant Gatherer, Derek Lahiri, Chandrajit Front Cell Infect Microbiol Cellular and Infection Microbiology Nosocomial infections have become alarming with the increase of multidrug-resistant bacterial strains of Acinetobacter baumannii. Being the causative agent in ~80% of the cases, these pathogenic gram-negative species could be deadly for hospitalized patients, especially in intensive care units utilizing ventilators, urinary catheters, and nasogastric tubes. Primarily infecting an immuno-compromised system, they are resistant to most antibiotics and are the root cause of various types of opportunistic infections including but not limited to septicemia, endocarditis, meningitis, pneumonia, skin, and wound sepsis and even urinary tract infections. Conventional experimental methods including typing, computational methods encompassing comparative genomics, and combined methods of reverse vaccinology and proteomics had been proposed to differentiate and develop vaccines and/or drugs for several outbreak strains. However, identifying proteins suitable enough to be posed as drug targets and/or molecular vaccines against the multidrug-resistant pathogenic bacterial strains has probably remained an open issue to address. In these cases of novel protein identification, the targets either are uncharacterized or have been unable to confer the most coveted protection either in the form of molecular vaccine candidates or as drug targets. Here, we report a strategic approach with the 3,766 proteins from the whole genome of A. baumannii ATCC19606 (AB) to rationally identify plausible candidates and propose them as future molecular vaccine candidates and/or drug targets. Essentially, we started with mapping the vaccine candidates (VaC) and virulence factors (ViF) of A. baumannii strain AYE onto strain ATCC19606 to identify them in the latter. We move on to build small networks of VaC and ViF to conceptualize their position in the network space of the whole genomic protein interactome (GPIN) and rationalize their candidature for drugs and/or molecular vaccines. To this end, we propose new sets of known proteins unearthed from interactome built using key factors, KeF, potent enough to compete with VaC and ViF. Our method is the first of its kind to propose, albeit theoretically, a rational approach to identify crucial proteins and pose them for candidates of vaccines and/or drugs effective enough to combat the deadly pathogenic threats of A. baumannii. Frontiers Media S.A. 2019-06-20 /pmc/articles/PMC6596342/ /pubmed/31281799 http://dx.doi.org/10.3389/fcimb.2019.00203 Text en Copyright © 2019 Mujawar, Mishra, Pawar, Gatherer and Lahiri. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Cellular and Infection Microbiology
Mujawar, Shama
Mishra, Rohit
Pawar, Shrikant
Gatherer, Derek
Lahiri, Chandrajit
Delineating the Plausible Molecular Vaccine Candidates and Drug Targets of Multidrug-Resistant Acinetobacter baumannii
title Delineating the Plausible Molecular Vaccine Candidates and Drug Targets of Multidrug-Resistant Acinetobacter baumannii
title_full Delineating the Plausible Molecular Vaccine Candidates and Drug Targets of Multidrug-Resistant Acinetobacter baumannii
title_fullStr Delineating the Plausible Molecular Vaccine Candidates and Drug Targets of Multidrug-Resistant Acinetobacter baumannii
title_full_unstemmed Delineating the Plausible Molecular Vaccine Candidates and Drug Targets of Multidrug-Resistant Acinetobacter baumannii
title_short Delineating the Plausible Molecular Vaccine Candidates and Drug Targets of Multidrug-Resistant Acinetobacter baumannii
title_sort delineating the plausible molecular vaccine candidates and drug targets of multidrug-resistant acinetobacter baumannii
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596342/
https://www.ncbi.nlm.nih.gov/pubmed/31281799
http://dx.doi.org/10.3389/fcimb.2019.00203
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