In silico characterization of hypothetical proteins from Orientia tsutsugamushi str. Karp uncovers virulence genes

Abstract

Scrub typhus also known as bush typhus is a disease with symptoms similar to Chikungunya infection. It is caused by a gram-negative bacterium Orientia tsutsugamushi which resides in its vertebrate host, Mites. The genome of Orientia tsutsugamushi str. Karp encodes for 1,563 proteins, of which 344 are characterized as hypothetical ones. In the present study, we tried to identify the probable functions of these 344 hypothetical proteins (HPs). All the characterized hypothetical proteins (HPs) belong to the various protein classes like enzymes, transporters, binding proteins, metabolic process and catalytic activity and kinase activity. These hypothetical proteins (HPs) were further analyzed for virulence factors with 62 proteins identified as the most virulent proteins among these hypothetical proteins (HPs). In addition, we studied the protein sequence similarity network for visualizing functional trends across protein superfamilies from the context of sequence similarity and it shows great potential for generating testable hypotheses about protein structure-function relationships. Furthermore, we calculated toplogical properties of the network and found them to obey network power law distributions showing a fractal nature. We also identifed two highly interconnected modules in the main network which contained five hub proteins (KJV55465, KJV56211, KJV57212, KJV57203 and KJV57216) having 1.0 clustering coefficient. The structural modeling (2D and 3D structure) of these five hub proteins was carried out and the catalytic site essential for its functioning was analyzed. The outcome of the present study may facilitate a better understanding of the mechanism of virulence, pathogenesis, adaptability to host and up-to-date annotations will make unknown genes easy to identify and target for experimentation. The information on the functional attributes and virulence characteristic of these hypothetical proteins (HPs) are envisaged to facilitate effective development of novel antibacterial drug targets of Orientia tsutsugamushi.

Characterization of sodium carboxymethyl cellulose/calcium alginate scaffold loaded with curcumin in skin tissue engineering

“…The prepared fibroblasts were transferred to DMEM enriched with 10% FBS, l ‐glutamine, penicillin G, and streptomycin and incubated in 5% carbon dioxide at 37°C and saturated humidity for 3 weeks. It should be noted that the medium was changed every 2 days to reach a cell density out of 80% and in the third passage, the cells were trypsinized 22 …”

“…It should be noted that the medium was changed every 2 days to reach a cell density out of 80% and in the third passage, the cells were trypsinized. 22…”

Glycoconjugates, hypothetical proteins, and post‐translational modification: Importance in host–pathogen interaction and antitubercular intervention development

“…Hypothetical proteins (HPs) are unidentified functioned proteins encrypted by expected open reading frames (ORF), but have no investigational proof of functions (Imam et al., 2019). Despite the bulk quantities of biological records such as genomic sequences, and functional genomic data from high‐throughput scrutinize, there is a scarcity in the convenient annotation.…”

“…These starring roles include structural proteins, enzymes, and the moving of elements inside and between cells (Browne et al., 2009). Likewise, this empowers their sorting into other paths and cascades that help as markers and pharmacological targets during drug discovery, and diagnosis especially in pathogens related to human diseases (Imam et al., 2019; Naveed et al., 2018). For instance, Li et al., (2010) identified 3 noble proteins (Rv1987, Rv3807, and Rv3887) via proteome scale investigation and recommends serving as an essential reference for developing new TB diagnostic methods and more effective tuberculosis vaccines.…”

An Educational Bioinformatics Project to Improve Genome Annotation

“…Several previously reported studies have used computational approaches to assign functional annotation to HPs in a wide range of bacterial and viral species, including but not limited to Staphylococcus aureus ( Mohan and Venugopal, 2012 ; School et al, 2016 ), M. tuberculosis ( Raj et al, 2017 ; Yang et al, 2019 ), Vibrio cholerae ( Islam et al, 2015 ), Klebsiella pneumoniae ( Pranavathiyani et al, 2020 ), Mycoplasma pneumoniae ( Shahbaaz et al, 2015 ), Orientia tsutsugamushi ( Imam et al, 2019 ), Corynebacterium pseudotuberculosis ( Araujo et al, 2020 ), human adenovirus ( Dorden and Mahadevan, 2015 ; Naveed et al, 2017 ), and vaccinia virus ( Mahmood et al, 2016 ). These studies utilize some combination of the various computational tools and databases available to analyze the physiochemical, functional, and structural properties of an HP ( Table 1 ) since results generated from a single server cannot provide a complete functional determination currently ( Dorden and Mahadevan, 2015 ).…”