Abstract
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.
Highlights
Nosocomial or hospital-acquired infections are among the multitude of diseases caused by the opportunistic pathogen Acinetobacter baumannii, one of the world’s six most important multidrug-resistant (MDR) microorganisms identified in hospitals (Talbot et al, 2006; Lin and Lan, 2014)
For the strain AYE, 168 proteins mentioned in the Supplementary Data 2 by Moriel et al (2013) were collected and categorized as vaccine candidates (VaC, Supplementary Data 1) while 124 from Supplementary Datas 3–5 reported by the same group were collated as virulent factors (ViF, Supplementary Data 2)
In order to the identify the potential molecular vaccine candidates and drug targets of MDR A. baumannii, we have started with the available pathogenic strains, namely, AYE
Summary
Nosocomial or hospital-acquired infections are among the multitude of diseases caused by the opportunistic pathogen Acinetobacter baumannii, one of the world’s six most important multidrug-resistant (MDR) microorganisms identified in hospitals (Talbot et al, 2006; Lin and Lan, 2014). The complications, resulting in an array of diseases caused by A. baumannii, arise from a plethora of virulence factors used by the pathogen to access and colonize the host system These include, but are obviously not limited to, porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles (OMVs), metal acquisition systems, and protein secretion systems (Lee et al, 2017). Further threats of infection arise from colonization outside the human host, mainly on medical devices, through the mechanism of biofilm production involving the associated pathways, proteins, secretion systems, and quorum sensing (Perez et al, 2007) With such a robust antibiotic resistance mechanism entailing a barrage of proteins comprising the host invading machinery, A. baumannii has been able to confer extensive drug resistance (XDR). Such ability has gone to the extent of evading almost every new-generation antibiotic, including carbapenems, which used to be prescribed to treat MDR organismal infections (Viehman et al, 2014)
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