Characterization of Antibiotic Resistance Determinants of Extended Spectrum β-lactamases Producing Enterobacteriaceae from Cancer Patients in South India

Patients with malignancy are highly prone to infections by Extended spectrum beta-lactamases producing Enterobacteriaceae (ESBL-PE). Knowledge on local resistance profile and resistance genes is essential to decide empirical drug. Hence, the study aims to find the resistance profile and the resistance genes of ESBL-PE from cancer patients. 172 oxyimino-cephalosporins resistant Enterobacterial isolates from clinical specimens of cancer patients were obtained. Study isolates were speciated by conventional biochemical methods. Resistance to antibiotics was detected by disc diffusion method. Phenotypic detection of ESBLs was performed as stated in CLSI guidelines. Genotypic characterization of resistance determinants of ESBL-PE was done by PCR. Among 172 Enterobacterial isolates, 151 (87.7%) were ESBL producers. E. coli (67.5%) was the major species producing ESBL enzymes followed by K. pneumoniae (27.8%). Antibiotic susceptibility pattern showed lowest resistance to imipenem 11.2%, and netilmicin 13.9%. 72% of ESBL-PE was found to be Multidrug-resistant. Among ESBL genes, blaCTX M gp-1 (83.4%) was dominant followed by blaTEM (32.4%) and blaSHV (27.8%). 36% of the isolates were found to be positive for more than one ESBL gene. High level of plasmid encoding quinolone resistance genes (64.2%) was identified in ESBL-PE. Low levels of plasmid mediated AmpC gene (15.8%) and 16S rRNA genes (9.2%) were found in ESBL-PE. The predominant ESBL encoding gene belongs to blaCTX M group 1. High proportion of ESBL-PE was found to co-harbor PMQR genes. ESBL-PE had highest sensitivity for imipenem and netilmicin

A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration

Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10−109); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10−9) and by 15.57-fold (P = 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number

Association of ADH1C and ALDH2 genes with alcohol dependence in south Indian Tamilian population: A case control approach

Objectives: Alcohol dependence (AD) poses a serious medical problem and significant public health issue contributing to morbidity and mortality throughout the world. The aim of the study was to establish the allele and genotype frequencies and to test the association of rs698 (ADH1C) and rs671(ALDH2) with the risk of alcohol dependence in south Indian Tamilian population. Methodology: A total of 150 alcohol dependent cases aged between 18- and 65-years fulfilling DSM-V criteria were recruited from the de-addiction centre. Blood donors (n=150) who had a history of alcohol intake with AUDIT score of less than eight were selected for the control group. The alleles were genotyped using TaqMan SNP genotyping assays by quantitative PCR. Association with alcohol dependence was evaluated with various genetic models using the Chi-square test. Multiple logistic regression analysis was performed to explore the effect of covariates. Results: The observed genotype frequency distributions of rs698 and rs671 were in agreement with Hardy Weinberg equilibrium (p>0.05).The dominant and allelic genetic model of ALDH2, rs671 between cases and controls showed a statistically significant association of the genetic variant with AD.&nbsp

Biological and structural properties’ interpretation on antitumour drug 3-(2-aminoethyl) indole (tryptamine) using molecular spectroscopy and computational tools

In this work, the known and unknown structural as well as biological properties of 3-(2-aminoethyl) indole (tryptamine) were interpreted using molecular spectroscopy (FT-IR, FT-Raman, NMR and UV–Visible) and cheminformatic tools. The supportive drug-related information was gained by analysing the obtained data which will be useful for the drug chemist for the pharmaceutical research. The important biological properties of the present chemical species satisfied the Lipinski five rules and it was opt to fabricate complex antibiotic compounds. The acquired charge potential load for creating antibiotic strain on compositional parts was keenly observed from the obtained data and it was evaluated by the vibrational analysis and Mulliken charge profile. From the NMR data, the chemical nodal points were noted and their movement around the molecule was carefully monitored. The degenerate and non-degenerate energy profile of orbital interaction system was studied and the link of chemical reactivity path was identified. The significance of excited electronic transitions among non-bonding molecular orbital system was justified and their transitional energy coefficient was determined. The toxicity level was checked from the chirality characteristics and enantiomer structure obtained from vibrational circular dichroism profile

Synthetic Biology’s Latest Trends in Antimicrobial Resistance and Biofilm

Recent instances of novel biological circuits that enable cells to gain biosynthetic skills demonstrate synthetic biology’s therapeutic potential. Synthetic biology is a branch of biology whose primary role is to build completely functional biological systems from the smallest basic elements such as DNA, proteins, and other organic molecules to complex bacteria. This review briefly mentions some novel way of synthetic strategies like bacterial modelling, two-component systems, synthetic peptide, and synthetic flavonoids used for targeting biofilm and drug-stable microbial communities. Bacterial modelling was mainly done in Escherichia coli and Mycoplasma using different strategies like introducing quorum sensing devices and CRISPR-mediated editing. Synthetic peptides are also one of the extensively studied ongoing areas which are produced from natural peptides taking as a template and altering amino acid position. Flavonoids are produced by two-step reaction and molecular hybridization methods. This kind of synthetic approach reported significant biofilm dispersion and lethal effects on clinically relevant bacteria like Pseudomonas aeruginosa, Staphylococcus aureus, E. coli, Acinetobacter baumannii, and Streptococcus species and Klebsiella pneumonia

A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration.

Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10(-109)); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10(-9)) and by 15.57-fold (P = 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number

Correction: A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration.

[This corrects the article DOI: 10.1371/journal.pone.0025598.]