Abstract

Acinetobacter baumannii (A. baumannii), an opportunistic, gram-negative pathogen, has evoked the interest of the medical community throughout the world because of its ability to cause nosocomial infections, majorly infecting those in intensive care units. It has also drawn the attention of researchers due to its evolving immune evasion strategies and increased drug resistance. The emergence of multi-drug-resistant-strains has urged the need to explore novel therapeutic options as an alternative to antibiotics. Due to the upsurge in antibiotic resistance mechanisms exhibited by A. baumannii, the current therapeutic strategies are rendered less effective. The aim of this study is to explore novel therapeutic alternatives against A. baumannii to control the ailed infection. In this study, a computational framework is employed involving, pan genomics, subtractive proteomics and reverse vaccinology strategies to identify core promiscuous vaccine candidates. Two chimeric vaccine constructs having B-cell derived T-cell epitopes from prioritized vaccine candidates; APN, AdeK and AdeI have been designed and checked for their possible interactions with host BCR, TLRs and HLA Class I and II Superfamily alleles. These vaccine candidates can be experimentally validated and thus contribute to vaccine development against A. baumannii infections.

Highlights

  • Acinetobacter baumannii (A. baumannii), an opportunistic, gram-negative pathogen, has evoked the interest of the medical community throughout the world because of its ability to cause nosocomial infections, majorly infecting those in intensive care units

  • A number of risk factors are reported to be associated with colonization and infection, some of which majorly involve prolonged period of hospital stay, frequent visits to intensive care settings, insertion of endotracheal tube during mechanical ventilation, colonization pressure (CP), subjection to antimicrobial therapeutic agents, freshly performed invasive surgical processes, and underlying sickness ­intensity[10,11]

  • Clusters of Orthologous Groups (COG) distribution analysis revealed that most of the core proteome was involved in metabolic regulation and biogenesis while the unique genes were linked to the storage and processing of information

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Summary

Introduction

Acinetobacter baumannii (A. baumannii), an opportunistic, gram-negative pathogen, has evoked the interest of the medical community throughout the world because of its ability to cause nosocomial infections, majorly infecting those in intensive care units. It has drawn the attention of researchers due to its evolving immune evasion strategies and increased drug resistance. The rapidly evolving nature of its multi-drug resistant strains (MDR) is a cause of concern and is responsible for approximately 2–10% of all gram-negative hospital-acquired infections in intensive care units (ICUs)[2]. Several endemic Acinetobacter strains frequently cohabit epidemic clones, making it almost impossible to recognize and control pathogen t­ ransmission[14,15]

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