Proteomic analysis of streptomycin resistant and sensitive clinical isolates of Mycobacterium tuberculosis

<p>Abstract</p> <p>Background</p> <p>Streptomycin (SM) is a broad spectrum antibiotic and is an important component of any anti-tuberculosis therapy regimen. Several mechanisms have been proposed to explain the emergence of resistance but still our knowledge is inadequate. Proteins form a very complex network and drugs are countered by their modification/efflux or over expression/modification of targets. As proteins manifest most of the biological processes, these are attractive targets for developing drugs, immunodiagnostics or therapeutics. The aim of present study was to analyze and compare the protein profile of whole cell extracts from <it>Mycobacterium tuberculosis </it>clinical isolates susceptible and resistant to SM.</p> <p>Results</p> <p>Two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was employed for analyzing the protein profiles. Homology and <it>in silico </it>characterization for identified proteins was assessed using BLAST, InterProScan and KEGG database searches. Computational studies on the possible interactions between SM and identified proteins were carried out by a battery of online servers and softwares, namely, CLUSTALW (KEGG), I-TASSER, VMD, PatchDock and FireDock. On comparing 2DE patterns, nine proteins were found consistently overexpressed in SM resistant isolates and were identified as Rv0350, Rv0440, Rv1240, Rv3075c, Rv2971, Rv3028c, Rv2145c, Rv2031c and Rv0569. <it>In silico </it>docking analysis showed significant interactions of SM with essential (Rv0350, Rv0440 and Rv2971) and non essential (Rv1240, Rv3075c and Rv2031c) genes.</p> <p>Conclusions</p> <p>The computational results suggest high protein binding affinity of SM and suggested many possible interactions between identified proteins and the drug. Bioinformatic analysis proves attributive for analysis of diversity of proteins identified by whole proteome analysis. In-depth study of the these proteins will give an insight into probable sites of drug action other than established primary sites and hence may help in search of novel chemotherapeutic agents at these new sites as inhibitors.</p

Prevalence of autism spectrum disorder and autistic symptoms in a school-based cohort of children in Kolkata, India

Despite housing ∼18% of the world's population, India does not yet have an estimate of prevalence of autism. This study was carried out to estimate the prevalence of autism in a selected population of school-children in India. N = 11,849 children (mean age = 5.9 [SD = 1.3], 39.5% females) were selected from various school types from three boroughs in Kolkata, India. Parents/caregivers and teachers filled in the social and communication disorders checklist (SCDC). Children meeting cutoff on parent-reported SCDC were followed up with the social communication questionnaire (SCQ). SCQ-positive children were administered the autism diagnostic observation schedule (ADOS). Teacher report on SCDC was available on all 11,849 children. Parent-report SCDC scores were obtained for 5,947 children. Mean scores on teacher SCDC were significantly lower than parent SCDC. Out of 1,247 SCDC-positive children, 882 answered the SCQ, of whom 124 met the cutoff score of 15. Six of these children met criteria for autism, autism spectrum disorder (ASD), or broader autism spectrum on the ADOS. The weighted estimate of supra-threshold SCQ scores was 3.54% (CI: 2.88–4.3%). The weighted prevalence estimate of positive scores (for broader autism spectrum + ASD + autism) was 0.23% (0.07–0.46%). As ∼20% children in this state are known to be out of the school system, and ASD prevalence is likely to be higher in this group, this estimate is likely to represent the lower-bound of the true prevalence. This study provides preliminary data on the prevalence of broader-spectrum autism and supra-threshold autistic traits in a population sample of school children in Eastern India

Marker-assisted enhancement of bacterial blight (Xanthomonas oryzae pv. oryzae) resistance in a salt-tolerant rice variety for sustaining rice production of tropical islands

IntroductionBacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae is a major disease of rice, specially in the tropical regions of the world. Developing rice varieties with host resistance against the disease is the most effective and economical solution for managing the disease.MethodsPyramiding resistance genes (Xa4, xa5, xa13,and Xa21) in popular rice varieties using marker-assisted backcross breeding (MABB) has been demonstrated as a cost-effective and sustainable approach for establishing durable BB resistance. Here, we report our successful efforts in introgressing four resistance genes (Xa4, xa5, xa13, and Xa21) from IRBB60 to CARI Dhan 5, a popular salt-tolerant variety developed from a somaclonal variant of Pokkali rice, through functional MABB.Results and discussionBoth BB and coastal salinity are among the major challenges for rice production in tropical island and coastal ecosystems. Plants with four, three, and two gene pyramids were generated, which displayed high levels of resistance to the BB pathogen at the BC3F2 stage. Under controlled salinity microplot environments, the line 131-2-175-1223 identified with the presence of three gene pyramid (Xa21+xa13+xa5) displayed notable resistance across locations and years as well as exhibited a salinity tolerance comparable to the recurrent parent, CARI Dhan 5. Among two BB gene combinations (Xa21+xa13), two lines, 17-1-69-334 and 46-3-95-659, demonstrated resistance across locations and years, as well as salt tolerance and grain production comparable to CARI Dhan 5. Besides salinity tolerance, five lines, 17-1-69-179, 46-3-95-655, 131-2-190-1197, 131-2-175-1209, and 131-2-175-1239, exhibited complete resistance to BB disease. Following multilocation testing, potential lines have been identified that can serve as a prospective candidate for producing varieties for the tropical Andaman and Nicobar Islands and other coastal locations, which are prone to BB and coastal salinity stresses

Drivers of vaccine hesitancy among vulnerable populations in India: a cross-sectional multi-state study

ObjectivesIndia’s Covid-19 vaccination campaign engaged frontline workers (FLWs) to encourage vaccination among vulnerable segments of society. The FLWs report encountering a variety of barriers to vaccination and are often unsuccessful despite multiple visits to the same person. This cross-sectional study aims to pinpoint which of these barriers drive vaccine hesitancy among these segments, to help streamline vaccine communication, including FLW training, to better safeguard the population.MethodsTrained field enumerators contacted 893 individuals from five states across India and collected self-reported assessments of fifteen vaccination barriers (identified through discussions with FLWs), current vaccination status and future vaccination intentions, and covariates (demographics/comorbidities). Factor analysis of the fifteen barriers yielded two factors, one relating to fear of vaccine adverse effects and a second focused on peripheral concerns regarding the vaccine. The covariates significantly associated with current vaccination status were combined under a latent class regime to yield three cluster types (health access, financial strength, and demographics). The primary analysis examined the effect of the two barrier factors, the covariate clusters, and comorbidity, on current vaccination status and future vaccine intentions.ResultsFear of vaccine adverse effects was the primary driver of vaccine hesitancy; peripheral concerns frequently mentioned by the FLWs had no impact. Although cluster membership and the presence of comorbidities predicted vaccine uptake, neither of them materially altered the effect of fear of vaccine adverse effects with the following exception: fear of adverse effects was not associated with vaccination status among young Muslim men.ConclusionSubject to limitations, these results indicate that interventions to decrease vaccine hesitancy should focus primarily on fear associated with vaccines rather than spend resources trying to address peripheral concerns