Bacteriophage vB_kpnS-Kpn15: Unveiling its potential triumph against extended-spectrum beta-lactamase-producing Klebsiella pneumoniae - Unraveling efficacy through innovative animal alternate models.

Aim -To isolate bacteriophages targeting extended-spectrum beta-lactamase-producing K. pneumoniae and evaluate their effectiveness across diverse models, incorporating innovative alternatives in animal testing. METHODS AND RESULTS: vB_kpnS-Kpn15 was isolated from sewage sample from Thane district. It produced a clear plaques on K. pneumoniae ATCC 700603. It has a flexible, non-contractile long tail and an icosahedral head and the Siphoviridae family of viruses in the order Caudovirales matched all of its structural criteria. Sequencing of vB_kpnS-Kpn15 revealed a 48,404 bp genome. The vB_KpnS-Kpn15 genome was found to contain 50 hypothetical proteins, of which 16 were found to possess different functions. The vB_KpnS-Kpn15 was also found to possess enzymes for its DNA synthesis. It was found to be lytic for the planktonic cells of K. pneumoniae and bactericidal for up to 48 h and potentially affected established K. pneumoniae biofilms. It demonstrated a broad host range and caused lytic zones on about 46 % of K. pneumoniae multi-drug resistant strains. In an in vitro wound and burn infection model, phage vB_kpnS-Kpn15 in combination with other phages resulted in successful cell proliferation and wound healing. Based on vB_kpnS-Kpn15's lytic properties, it can be incorporated in a bacteriophage cocktail to combat ESBL strains. CONCLUSIONS: The phages isolated during this research are better candidates for phage therapy, and therefore provide new and exciting options for the successful control of antibiotic-resistant bacterial infections in the future. The utilization of animal alternative models in this study elucidates cellular proliferation and migration, underscoring its significance in screening novel drugs with potential applications in the treatment of wound and burn infections. SIGNIFICANCE AND IMPACT OF THE RESEARCH: The findings of this research have implications for the creation of innovative, promising strategies to treat ESBL K. pneumoniae infections.

Pseudomonas aeruginosa: Infections and novel approaches to treatment "Knowing the enemy" the threat of Pseudomonas aeruginosa and exploring novel approaches to treatment.

Pseudomonas aeruginosa is an aerobic Gram-negative rod-shaped bacterium with a comparatively large genome and an impressive genetic capability allowing it to grow in a variety of environments and tolerate a wide range of physical conditions. This biological flexibility enables the P. aeruginosa to cause a broad range of infections in patients with serious underlying medical conditions, and to be a principal cause of health care associated infection worldwide. The clinical manifestations of P. aeruginosa include mostly health care associated infections and community-acquired infections. P. aeruginosa possesses an array of virulence factors that counteract host defence mechanisms. It can directly damage host tissue while utilizing high levels of intrinsic and acquired antimicrobial resistance mechanisms to counter most classes of antibiotics. P. aeruginosa co-regulates multiple resistance mechanisms by perpetually moving targets poses a significant therapeutic challenge. Thus, there is an urgent need for novel approaches in the development of anti-Pseudomonas agents. Here we review the principal infections caused by P. aeruginosa and we discuss novel therapeutic options to tackle antibiotic resistance and treatment of P. aeruginosa infections that may be further developed for clinical practice.

Chasing the personalized medicine dream through biomarker validation in colorectal cancer.

Colorectal cancer (CRC) is a major health burden worldwide. The optimal approach to the diagnosis, management, and treatment of CRC involves multidisciplinary and integrated management practices. The field is rapidly changing because of recent advancements in delineating the molecular basis of tumorigenesis, introduction of targeted therapy, varied patient response to mainstay chemotherapeutics, biological drugs, and the effective combination regimes being used for treatment. Recent meta-analysis studies, which tend to establish few clinically useful predictor biomarkers, identify inconsistent results and limitations of the trials. Therefore, molecular pathological epidemiology discipline initiatives are promising. Here, we provide an overview of the potential of biomarker validation for personalized medicine by focusing largely on metastatic (m)CRC. We also highlight new candidate predictive and prognostic biomarkers.

Regioselective synthesis of phenanthrenes and evaluation of their anti-oxidant based anti-inflammatory potential.

Regioselective synthesis of 9,10-dihydro-2,5-dimethoxyphenanthrene-1,7-diol (1) and 9,10-dihydro-2,7-dimethoxyphenanthrene-1,5-diol (2) was achieved using regioselective methylation, Wittig reaction, intramolecular cyclization and hydrogenation as key steps. The synthesis was successfully completed in total of 15 steps with 3.3% overall yield in case of 1 and in total of 13 steps with 9.0% overall yield in case of 2. All compounds (1-4) showed good antioxidant and anti-inflammatory activity in in vitro assays and these activities were found to be due the presence of phenolic hydroxyl groups.

KRAS gene mutations in correlation with clinicopathological features of colorectal carcinomas in Indian patient cohort.

KRAS gene mutations have been identified as a predictive molecular marker to predict the sensitivity of tumors to anti-EGFR therapeutics. The variability of clinical response to anti-EGFR agents has highlighted the need to select the appropriate patients who can benefit from the treatment. We examined the prevalence of KRAS mutations in 1,323 colorectal cancer patients from different regions of India and its correlation with geographic distribution and clinicopathological characteristics. DNA was extracted from formalin-fixed, paraffin-embedded tissue samples and was amplified by nested polymerase chain reaction at KRAS exon 2 and subjected to nucleotide sequencing using ABI 3100 Genetic Analyzer. The frequency of KRAS mutations was found to be 20.5 % (271/1,323). There was significant association (p < 0.05) between KRAS mutations, age and the tumor differentiation. Statistical analysis revealed significantly higher prevalence of colorectal cancer with mutated KRAS gene in northern regions of the country. No significant association was observed between KRAS mutations and gender (p > 0.05). Our study indicates that KRAS mutations in Indian colorectal cancer patients occur at lower level compared to that of Western population.

Maximization of recombinant Helicobacter pylori neutrophil activating protein production in Escherichia coli: improvement of a chemically defined medium using response surface methodology.

Medium optimization for the production of constitutive recombinant Helicobacter pylori neutrophil activating protein (NAP) in Escherichia coli was investigated by using response surface methodology. Carbon to nitrogen ratio, concentrations of sodium polyphosphate and magnesium sulfate were considered as independent variables. The optimized medium was a chemically defined medium with a carbon to nitrogen ratio of 14.4 and with concentrations of sodium polyphosphate and magnesium sulfate about 7.1 g l(-1) and 3.04 g l(-1) respectively. The maximum recombinant NAP production level (1184.6 mg l(-1)) was 29.96% higher than that in control medium.