Uropathogenic bacteria and deductive genomics towards antimicrobial resistance, virulence, and potential drug targets / Bacterias uropatógenas y genómica deductiva hacia la resistencia, virulencia y posibles objetivos farmacológicos a los antimicrobianos

Urinary tract infections (UTIs) are among the most prevalent bacterial infections affecting people in inpatient and outpatient settings. The current study aimed to sequence the genome of uropathogenic Escherichia coli strain CUI-B1 resourced from a woman having uncomplicated cystitis and pyelonephritis. Followed by deductive genomics towards potential drug targets using E. coli strain CUI-B1, strain O25b: H4-ST131, Proteus mirabilis strain HI4320, Klebsiella pneumoniae strain 1721, and Staphylococcus saprophyticus strain ATCC 15305 uropathogenic strains. Comparative genome analysis revealed that genes related to the survival of E. coli, P. mirabilis, K. pneumoniae, and S. saprophyticus, such as genes of metal-requiring proteins, defense-associated genes, and genes associated with general physiology, were found to be highly conserved in the genomes including strain CUI-B1. However, the genes responsible for virulence and drug resistance, mainly those that are involved in bacterial secretion, fimbriae, adherence, and colonization, were found in various genomic regions and varied from one species to another or within the same species. Based on the genome sequence, virulence, and antimicrobial-resistant gene dataset, the subtractive proteomics approach revealed 22 proteins mapped to the pathogen’s unique pathways and among them, entB, clbH, chuV, and ybtS were supposed to be potential drug targets and the single drug could be utilized for all above-mentioned strains. These results may provide the foundation for the optimal target for future discovery of drugs for E. coli-, P. mirabilis-, K. pneumoniae-, and S. saprophyticus-based infections and could be investigated further to employ in personalized drug development.(AU)

Uropathogenic bacteria and deductive genomics towards antimicrobial resistance, virulence, and potential drug targets.

Urinary tract infections (UTIs) are among the most prevalent bacterial infections affecting people in inpatient and outpatient settings. The current study aimed to sequence the genome of uropathogenic Escherichia coli strain CUI-B1 resourced from a woman having uncomplicated cystitis and pyelonephritis. Followed by deductive genomics towards potential drug targets using E. coli strain CUI-B1, strain O25b: H4-ST131, Proteus mirabilis strain HI4320, Klebsiella pneumoniae strain 1721, and Staphylococcus saprophyticus strain ATCC 15305 uropathogenic strains. Comparative genome analysis revealed that genes related to the survival of E. coli, P. mirabilis, K. pneumoniae, and S. saprophyticus, such as genes of metal-requiring proteins, defense-associated genes, and genes associated with general physiology, were found to be highly conserved in the genomes including strain CUI-B1. However, the genes responsible for virulence and drug resistance, mainly those that are involved in bacterial secretion, fimbriae, adherence, and colonization, were found in various genomic regions and varied from one species to another or within the same species. Based on the genome sequence, virulence, and antimicrobial-resistant gene dataset, the subtractive proteomics approach revealed 22 proteins mapped to the pathogen's unique pathways and among them, entB, clbH, chuV, and ybtS were supposed to be potential drug targets and the single drug could be utilized for all above-mentioned strains. These results may provide the foundation for the optimal target for future discovery of drugs for E. coli-, P. mirabilis-, K. pneumoniae-, and S. saprophyticus-based infections and could be investigated further to employ in personalized drug development.

Circ_0067934 as a novel therapeutic target in cancer: From mechanistic to clinical perspectives.

Circular RNAs, as a type of non-coding RNAs, are identified in a various cell. Circular RNAs have stable structures, conserved sequence, and tissue and cell-specific level. High throughput technologies have proposed that circular RNAs act via various mechanisms like sponging microRNAs and proteins, regulating transcription factors, and scaffolding mediators. Cancer is one of the major threat for human health. Emerging data have proposed that circular RNAs are dysregulated in cancers as well as are associated with aggressive behaviors of cancer -related behaviors like cell cycle, proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (EMT). Among them, circ_0067934 was shown to act as an oncogene in cancers to enhance migration, invasion, proliferation, cell cycle, EMT, and inhibit cell apoptosis. In addition, these studies have proposed that it could be a promising diagnostic and prognostic biomarker in cancer. This study aimed to review the expression and molecular mechanism of circ_0067934 in modulating the malignant behaviors of cancers as well as to explore its potential as a target in cancer chemotherapy, diagnosis, prognosis and treatment.