Chimeric vaccine designs against Acinetobacter baumannii using pan genome and reverse vaccinology approaches.

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.

PanRV: Pangenome-reverse vaccinology approach for identifications of potential vaccine candidates in microbial pangenome.

BACKGROUND: A revolutionary diversion from classical vaccinology to reverse vaccinology approach has been observed in the last decade. The ever-increasing genomic and proteomic data has greatly facilitated the vaccine designing and development process. Reverse vaccinology is considered as a cost-effective and proficient approach to screen the entire pathogen genome. To look for broad-spectrum immunogenic targets and analysis of closely-related bacterial species, the assimilation of pangenome concept into reverse vaccinology approach is essential. The categories of species pangenome such as core, accessory, and unique genes sets can be analyzed for the identification of vaccine candidates through reverse vaccinology. RESULTS: We have designed an integrative computational pipeline term as "PanRV" that employs both the pangenome and reverse vaccinology approaches. PanRV comprises of four functional modules including i) Pangenome Estimation Module (PGM) ii) Reverse Vaccinology Module (RVM) iii) Functional Annotation Module (FAM) and iv) Antibiotic Resistance Association Module (ARM). The pipeline is tested by using genomic data from 301 genomes of Staphylococcus aureus and the results are verified by experimentally known antigenic data. CONCLUSION: The proposed pipeline has proved to be the first comprehensive automated pipeline that can precisely identify putative vaccine candidates exploiting the microbial pangenome. PanRV is a Linux based package developed in JAVA language. An executable installer is provided for ease of installation along with a user manual at https://sourceforge.net/projects/panrv2/ .

Reverse Vaccinology Approach to Potential Vaccine Candidates Against Acinetobacter baumannii.

Acinetobacter baumannii is a rapidly evolving pathogen that largely inhabits intensive care units (ICU). This opportunistic, gram-negative organism has shown noteworthy taxonomic variations during the past three decades. A. baumannii functions as a catalase-positive, oxidase-negative obligate, aerobic, nonmotile, highly infectious, and multidrug-resistant bacterium. Therefore, the infection caused by this bacterium tends to have a fairly higher incidence rate in immune-compromised individuals ranging from 26.5% to 91%, as it colonizes in skin tissues and secretions of the respiratory tract. Recently, it has been globally labeled as a "red alert" pathogen, setting alarms throughout the medical community, arising mainly due to its widespread antibiotic resistance continuum. There is a dire need for alternative therapeutic intervention to combat A. baumannii-associated infections and the growing resistance. This chapter focuses upon the reverse vaccinology-based steps and strategies to identify novel potential vaccine candidates against this emerging pathogen.

Draft Genome Sequence of a Salmonella enterica Serovar Typhi Strain Resistant to Fourth-Generation Cephalosporin and Fluoroquinolone Antibiotics.

Typhoid is endemic in developing countries. We report here the first draft genome sequence of a Salmonella enterica serovar Typhi clinical isolate from Pakistan exhibiting resistance to cefepime (a fourth-generation cephalosporin) and fluoroquinolone antibiotics, two of the last-generation therapies against this pathogen. The genome is ~4.8 Mb, with two putative plasmids.