Exploring Computational and Biophysical Tools to Study the Presence of G-Quadruplex Structures: A Promising Therapeutic Solution for Drug-Resistant Vibrio cholerae

Vibrio cholerae, a gram-negative bacterium that causes cholera, has already caused seven major pandemics across the world and infects roughly 1.3–4 million people every year. Cholera treatment primarily involves oral rehydration therapy supplemented with antibiotics. But recently, multidrug-resistant strains of V. cholerae have emerged. High genomic plasticity further enhances the pathogenesis of this human pathogen. Guanines in DNA or RNA assemble to form G-quadruplex (GQ) structures which have begun to be seen as potential drug targeting sites for different pathogenic bacteria and viruses. In this perspective, we carried out a genome-wide hunt in V. cholerae using a bio-informatics approach and observed ∼85 G-quadruplex forming motifs (VC-PGQs) in chromosome I and ∼45 putative G-quadruplexs (PGQs) in chromosome II. Ten putative G-quadruplex forming motifs (VC-PGQs) were selected on the basis of conservation throughout the genus and functional analysis displayed their location in the essential genes encoding bacterial proteins, for example, methyl-accepting chemotaxis protein, orotate phosphoribosyl transferase protein, amidase proteins, etc. The predicted VC-PGQs were validated using different bio-physical techniques, including Nuclear Magnetic Resonance spectroscopy, Circular Dichroism spectroscopy, and electrophoretic mobility shift assay, which demonstrated the formation of highly stable GQ structures in the bacteria. The interaction of these VC-PGQs with t...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research

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Authors: Reissier S, Cattoir V Abstract INTRODUCTION: Streptogramins (pristinamycin and quinupristin-dalfopristin) can be interesting options for the treatment of infections due to Gram-positive cocci, especially multidrug-resistant isolates. AREAS COVERED: This review provides an updated overview on structural and activity characteristics, mechanisms of action and resistance, pharmacokinetic/pharmacodynamic and clinical use of streptogramins. EXPERT OPINION: The streptogramin antibiotics act by inhibition of the bacterial protein synthesis. They are composed of two chemically distinct compounds, namely typ...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
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This study reports the occurrence of multidrug resistant V. cholerae O1 in Lake Victoria that are genetically closely related to recent pandemic strains in Tanzania, Kenya and Uganda. The strains identified are also closely related to older pandemic strains recovered in the Democratic Republic of Congo, Burundi and Tanzania up until 1993, suggesting a long-term persistence and wide spatial distribution of pandemic strains within the region with the lake serving as a reservoir. These environmental isolates likely emerged from previous cholera outbreaks and survived in the lake environment for decades through various relatio...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
The seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublin...
Source: ScienceNOW - Category: Science Authors: Tags: Medicine, Diseases, Microbiology reports Source Type: news
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