Zarrin Basharat

Comparative Evaluation of MRSA Nasal Colonization Epidemiology in the Urban and Rural Secondary School Community of Kurdistan, Iraq

Background To study the nasal carriage rate of Staphylococcus aureus (S. aureus) (including methicillin-resistant strains) in secondary school community of the urban and rural districts of the Kurdistan region of Iraq, a cross-sectional population based survey was carried out in the city Duhok and rural areas of Amedya, Akre and Zakho. Methods Nasal swabs were obtained from nostrils of 509 students aged 14-23 years. Resistance to methicillin was assessed by Kirby-Bauer disk diffusion and agar dilution assay. Vancomycin sensitivity was also tested on Muller-Hinton agar. Results It was found that the frequency of overall S. aureus nasal carriage (SANC) was 17.75% (90/509, CI95, 14.58–21.42%). In urban areas, the carriage rate was 20.59% (49/239, CI95, 15.64–26.29%), whereas it was 15.24% (41/270, CI95, 11.17–20.10%) in rural districts. The frequency of methicillin-resistant S. aureus (MRSA) among the isolated strains was found to be 2.04% (1/49) and 21.95% (9/41) in urban and rural areas respectively. It was found that in urban residents, the odd ratio (OR) of acquiring SANC was 1.44 (CI95, 0.91-2.27%) and risk ratio (RR) was at least 1.35 (CI95, 0.92-1.96%) while OR decreased to 0.12 (CI95, 0.01-0.96%) for MRSA carriage. Hence, the S. aureus carriage rate was higher in urban districts compared to rural areas while more MRSA were found in rural areas compared to urban districts. All studied strains were sensitive to vancomycin. Conclusion This study provided baseline information for S. aureus nasal colonization in the region. Also, it showed that living in rural areas increased the odds of MRSA colonization. More attention should be paid to control MRSA colonization in rural communities.

In silico assessment of phosphorylation and O-β-GlcNAcylation sites in human NPC1 protein critical for Ebola virus entry.

Ebola is a highly pathogenic enveloped virus responsible for deadly outbreaks of severe hemorrhagic fever. It enters human cells by binding a multifunctional cholesterol transporter Niemann-Pick C1 (NPC1) protein. Post translational modification (PTM) information for NPC1 is crucial to understand Ebola virus (EBOV) entry and action due to changes in phosphorylation or glycosylation at the binding site. It is difficult and costly to experimentally assess this type of interaction, so in silico strategy was employed. Identification of phosphorylation sites, including conserved residues that could be possible targets for 21 predicted kinases was followed by interplay study between phosphorylation and O-β-GlcNAc modification of NPC1. Results revealed that only 4 out of 48 predicted phosphosites exhibited O-β-GlcNAc activity. Predicted outcomes were integrated with residue conservation and 3D structural information. Three Yin Yang sites were located in the α-helix regions and were conserved in studied vertebrate and mammalian species. Only one modification site S425 was found in β-turn region located near the N-terminus of NPC1 and was found to differ in pig, mouse, cobra and humans. The predictions suggest that Yin Yang sites may not be important for virus attachment to NPC1, whereas phosphosite 473 may be important for binding and hence entry of Ebola virus. This information could be useful in addressing further experimental studies and therapeutic strategies targeting PTM events in EBOV entry.

Understanding properties of the master effector of phage shock operon in Mycobacterium tuberculosis via bioinformatics approach

The phage shock protein (Psp) is a part of the Psp operon, which assists in safeguarding the survival of bacterium in stress and shields the cell against proton motif force challenge. It is strongly induced by bacterium allied phages, improperly localized mutant porins and various other stresses. Master effector of the operon, PspA has been modeled and simulated, illustrating how it undergoes significant conformational transition at the far end in Mycobacterium tuberculosis. Association of this key protein of the operon influences action of Psp system on the whole. We are further working on the impact of phosphorylation perturbation and changes in the structure of PspA during complex formation with other moieties of interest.

NQO1 rs1800566 polymorph is more prone to NOx induced lung injury: Endorsing deleterious functionality through informatics approach

Gene-environment interaction studies have led to the identification of genetic mutations in individuals with increased susceptibility to pollution related diseases. rs1800566 polymorphism of NQO1, leading to P187S missense mutation in the transcribed antioxidant protein, causes individuals carrying this mutation more prone to NO2 induced lung inflammatory injury. Here, we report significant structural and functional changes incurred by NQO1 antioxidant protein as a result of alteration in its nucleotide (C609T) and hence, protein sequence. Detailed insights were obtained regarding the prospective impact of this mutation on the structural stability of normal and mutated NQO1 protein, using a myriad of bioinformatic tools and webservers. Structure analysis showed no significant change at secondary level. A change in the native backbone conformation was observed due to formation of a hydrogen bond. Hydrophobicity and phosphorylation properties, decisive factors for functioning and stability of NQO1 were considerably influenced by P187S mutation. Computational study of the properties of a polymorph linked with NOx induced lung injury sheds light on the molecular basis of this polymorphism and endorses previous findings, reported by the scientists working in this domain.

Distribution analysis of profilin isoforms at transcript resolution with mRNA-seq and secondary structure in various organs of Rattus norvegicus.

Profilin (Pfn) is an actin binding protein, ubiquitously found in mammals and is essential for the actin polymerization in cells. In brain, it plays a pivotal role in neurogenesis and synapse formation by interacting with various proteins. Four Pfn isoforms have been identified in mammals. This study presents the identification and transcriptional expression of various Pfn isoforms (Pfn1, Pfn2, Pfn3 and Pfn4) in brain, heart, kidney, liver, and muscle and testis of Rattus norvegicus. Organs have been classified into groups based on some similarities. Group I includes brain and testis, Group II includes skeletal muscle and heart, while Group III includes kidney and liver. Pfn1 has been identified in all groups, Pfn2 and Pfn3 have been identified in group I, group III and in one organ (skeletal muscle) of group II. To the best of the authors knowledge, no report of Pfn1 and Pfn2 presence in testis, Pfn3 in brain, liver and skeletal muscle, Pfn4 in kidney and skeletal muscle exists to date. Transcriptional expression showed variations among expression level of different Pfn isoforms in various organs with respect to the control gene GADPH. We hypothesize that this could be attributed to profilin isoform specific mRNA structure and corresponding motifs, which generally contribute to similar or varied decay rates, cellular localization, post transcriptional regulation pattern and ligand binding.

Genome Editing Weds CRISPR: What Is in It for Phytoremediation?

The arrival of sequence-specific endonucleases that allow genome editing has shaken the pillars of basic and applied plant biology. Clustered regularly interspaced palindromic repeats (CRISPR) is a revolutionary genome-engineering tool that enables the enhancement of targeted traits in plants. Numerous plants, including energy crops, known for their potential to tolerate, immobilize, and stabilize inorganic and organic pollutants, have already been edited using different CRISPR systems. Moreover, a large array of genes responsible for increased metal tolerance, metal uptake and hyperaccumulation have already been identified. Thus, the CRISPR-mediated genome reprogramming of plants, including its use in gene expression regulation through transcriptional repression or activation (CRISPRi and CRISPRa), could be of paramount importance for phytoremediation. The simplicity, inexpensiveness, and capabilities of this gene editing technique could soon be used to enhance plants and bacteria involved in phytotechnologies, such as phystabilization, phytoextraction, phytomining, phytovolatilization, and bio-energy generation. In this brief viewpoint piece, we posit some of the potential benefits of CRISPR for phytoremediation.

Bioinformatic analysis of human Gαq Q209 missense mutations associated with uveal melanoma

Uveal melanoma is the most common primary intraocular tumor in adults. GNAQ gene missense mutations at position 209 have been reported to be associated with this type of cancer. Q209 mutations occurring within the catalytic (GTPase) domain of Guanine nucleotide protein subunit alpha polypeptide q (Gαq) encoded by GNAQ gene have been analyzed computationally in this study to elucidate hydrophobic, phosphorylative and structural changes associated with these mutations. When compared to wild-type, molecular effect variations of hydropathicity, instability and phosphorylation were observed in the mutant proteins leading to pathogenecity. Protein-protein interaction study of the wild type GNAQ and Q209 mutants were also studied. This information can aid drug research targeting Q209 in uveal mylenoma as no direct anti-GNAQ therapies are available for this cancer presently.

Survey of compound microsatellites in multiple Lactobacillus genomes

Distinct simple sequence repeats with 2 or more individual microsatellites joined together or lying adjacent to each other are identified as compound microsatellites. Investigation of such composite microsatellites in the genomes of genus Lactobacillus was the aim of this study. In silico inspection of microsatellite clustering in genomes of 14 Lactobacillus species revealed a wealth of compound microsatellites. All of the mined compound microsatellites were imperfect, were composed of variant motifs, and increased in all genomes, with maximum distance (dMAX) increments of 10 to 50. The majority of these repeats were present in the coding regions. A correlation of microsatellite to compound microsatellite density was detected. The difference established in compound microsatellite division among eukaryotes, Escherichia coli, and lactobacilli is suggestive of diverse genomic features and elementary distinction between creation and fixation methods of compound microsatellites among these organisms.

Digital dissection of arsenate reductase enzyme from an arsenic hyperccumulating fern Pteris vittata

Action of arsenate reductase is crucial for the survival of an organism in arsenic polluted area. Pteris vittata, also known as Chinese ladder brake, was the first identified arsenic hyperaccumulating fern with the capability to convert [As(V)] to arsenite [As(III)]. This study aims at sequence analysis of the most important protein of the arsenic reduction mechanism in this specie. Phosphorylation potential of the protein along with possible interplay of phosphorylation with O-β-GlcNAcylation was predicted using neural network based webservers. Secondary and tertiary structure of arsenate reductase was then analysed. Active site region of the protein comprised a rhodanese-like domain. Cursory dynamics simulation revealed that folds remained conserved in the rhodanese main but variations were observed in the structure in other regions. This information sheds light on the various characteristics of the protein and may be useful to enzymologists working on the improvement of its traits for arsenic reduction.

Drug target identification and virtual screening in pursuit of phytochemical intervention of Mycobacterium chelonae

Mycobacterium chelonae is a rapidly growing mycobacterium present in the environment. It is associated with skin and soft tissue infections including abscess, cellulitis and osteomyelitis. Other infections by this bacterium are post-operative/transplant-associated, catheter, prostheses and even concomitant to haemodialytic procedures. In this study, we employ a subtractive genomics approach to predict the potential therapeutic candidates, intended for experimental research against this bacterium. A computational workflow was devised and executed to procure core proteome targets essential to the pathogen but with no similarity to the human host. Initially, essential Mycobacterium chelonae proteins were predicted through homology searching of core proteome content from 19 different bacteria. Druggable proteins were then identified and N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) was chosen as a case study from identified therapeutic targets, based on its important bifunctional role. Structure modeling was followed by virtual screening of phytochemical library (N > 2200), from 500 medicinal plants, against it. A biflavonoid daphnodorin G from Daphne odora was screened as having best potential for binding GlmU. Phytotherapy helps curb the menace of antibiotic resistance so treatment of Mycobacterium chelonae infection through this method is recommended.