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Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance where the drugs are no longer effective. Fungi evolve antifungal resistance, viruses evolve antiviral resistance, protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic resistance. Together all of these come under the umbrella of antimicrobial resistance. Microbes resistant to multiple antimicrobials are called multidrug resistant (MDR) and are sometimes referred to as superbugs. Although antimicrobial resistance is a naturally occurring process, it is often the result of improper usage of the drugs and management of the infections.
Escherichia coli ( ESH-ə-RIK-ee-ə KOH-ly) is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus Escherichia that is commonly found in the lower intestine of warm-blooded organisms. Most E. coli strains are harmless, but some serotypes such as EPEC, and ETEC are pathogenic and can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination incidents that prompt product recalls. Most strains are part of the normal microbiota of the gut and are harmless or even beneficial to humans (although these strains tend to be less studied than the pathogenic ones). For example, some strains of E. coli benefit their hosts by producing vitamin K2 or by preventing the colonization of the intestine by pathogenic bacteria. These mutually beneficial relationships between E. coli and humans are a type of mutualistic biological relationship — where both the humans and the E. coli are benefitting each other. E. coli is expelled into the environment within fecal matter. The bacterium grows massively in fresh fecal matter under aerobic conditions for three days, but its numbers decline slowly afterwards.
The SOS response is a global response to DNA damage in which the cell cycle is arrested and DNA repair and mutagenesis is induced. The system involves the RecA protein. The RecA protein, stimulated by single-stranded DNA, is involved in the inactivation of the repressor (LexA) of SOS response genes thereby inducing the response. It is an error-prone repair system that contributes significantly to DNA changes observed in a wide range of species.
Polymyxins are antibiotics. Polymyxins B and E are used in the treatment of Gram-negative bacterial infections. They work mostly by breaking up the bacterial cell membrane. They are part of a broader class of molecules called nonribosomal peptides.
The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism. The small molecule chemicals found in a given metabolome may include both endogenous metabolites that are naturally produced by an organism as well as exogenous chemicals that are not naturally produced by an organism.
The Biological General Repository for Interaction Datasets (BioGRID) is a curated biological database of protein-protein interactions, genetic interactions, chemical interactions, and post-translational modifications created in 2003 (originally referred to as simply the General Repository for Interaction Datasets by Mike Tyers, Bobby-Joe Breitkreutz, and Chris Stark at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital. It strives to provide a comprehensive curated resource for all major model organism species while attempting to remove redundancy to create a single mapping of data. Users of The BioGRID can search for their protein, chemical or publication of interest and retrieve annotation, as well as curated data as reported, by the primary literature and compiled by in house large-scale curation efforts. The BioGRID is hosted in Toronto, Ontario, Canada and Dallas, Texas, United States and is partnered with the Saccharomyces Genome Database, FlyBase, WormBase, PomBase, and the Alliance of Genome Resources. The BioGRID is funded by the NIH and CIHR. BioGRID is an observer member of the International Molecular Exchange Consortium.
In bioinformatics EcoCyc is a biological database for the bacterium Escherichia coli K-12. The EcoCyc project performs literature-based curation of the E. coli genome, and of E. coli transcriptional regulation, transporters, and metabolic pathways. EcoCyc contains written summaries of E. coli genes, distilled from over 36,000 scientific articles. EcoCyc is also a description of the genome and cellular networks of E. coli that supports scientists to carry out computational analyses.
Cefoxitin is a second-generation cephamycin antibiotic developed by Merck & Co., Inc. from Cephamycin C in the year following its discovery, 1972. It was synthesized in order to create an antibiotic with a broader spectrum. It is often grouped with the second-generation cephalosporins. Cefoxitin requires a prescription and as of 2010 is sold under the brand name Mefoxin by Bioniche Pharma, LLC. The generic version of cefoxitin is known as cefoxitin sodium.
Computational Resources for Drug Discovery (CRDD) is one of the important silico modules of Open Source for Drug Discovery (OSDD). The CRDD web portal provides computer resources related to drug discovery on a single platform. It provides computational resources for researchers in computer-aided drug design, a discussion forum, and resources to maintain a wiki related to drug discovery, predict inhibitors, and predict the ADME-Tox property of molecules. One of the major objectives of CRDD is to promote open source software in the field of chemoinformatics and pharmacoinformatics.
Bacterial small RNAs (bsRNA) are small RNAs produced by bacteria; they are 50- to 500-nucleotide non-coding RNA molecules, highly structured and containing several stem-loops. Numerous sRNAs have been identified using both computational analysis and laboratory-based techniques such as Northern blotting, microarrays and RNA-Seq in a number of bacterial species including Escherichia coli, the model pathogen Salmonella, the nitrogen-fixing alphaproteobacterium Sinorhizobium meliloti, marine cyanobacteria, Francisella tularensis, Streptococcus pyogenes, the pathogen Staphylococcus aureus, and the plant pathogen Xanthomonas oryzae pathovar oryzae. Bacterial sRNAs affect how genes are expressed within bacterial cells via interaction with mRNA or protein, and thus can affect a variety of bacterial functions like metabolism, virulence, environmental stress response, and structure.
Plasmid-mediated resistance is the transfer of antibiotic resistance genes which are carried on plasmids. Plasmids possess mechanisms that ensure their independent replication as well as those that regulate their replication number and guarantee stable inheritance during cell division. By the conjugation process, they can stimulate lateral transfer between bacteria from various genera and kingdoms. Numerous plasmids contain addiction-inducing systems that are typically based on toxin-antitoxin factors and capable of killing daughter cells that don't inherit the plasmid during cell division. Plasmids often carry multiple antibiotic resistance genes, contributing to the spread of multidrug-resistance (MDR). Antibiotic resistance mediated by MDR plasmids severely limits the treatment options for the infections caused by Gram-negative bacteria, especially family Enterobacteriaceae. The global spread of MDR plasmids has been enhanced by selective pressure from antimicrobial medications used in medical facilities and when raising animals for food.
Escherichia coli is a gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms (endotherms). Most E. coli strains are harmless, but pathogenic varieties cause serious food poisoning, septic shock, meningitis, or urinary tract infections in humans. Unlike normal flora E. coli, the pathogenic varieties produce toxins and other virulence factors that enable them to reside in parts of the body normally not inhabited by E. coli, and to damage host cells. These pathogenic traits are encoded by virulence genes carried only by the pathogens.
Enteroaggregative Escherichia coli are a pathotype of Escherichia coli which cause acute and chronic diarrhea in both the developed and developing world. They may also cause urinary tract infections. EAEC are defined by their "stacked-brick" pattern of adhesion to the human laryngeal epithelial cell line HEp-2. The pathogenesis of EAEC involves the aggregation of and adherence of the bacteria to the intestinal mucosa, where they elaborate enterotoxins and cytotoxins that damage host cells and induce inflammation that results in diarrhea.
The mobilized colistin resistance (mcr) gene confers plasmid-mediated resistance to colistin, one of a number of last-resort antibiotics for treating Gram-negative infections. mcr-1, the original variant, is capable of horizontal transfer between different strains of a bacterial species. After discovery in November 2015 in E. coli from a pig in China it has been found in Escherichia coli, Salmonella enterica, Klebsiella pneumoniae, Enterobacter aerogenes, and Enterobacter cloacae. As of 2017, it has been detected in more than 30 countries on 5 continents in less than a year.
The Comprehensive Antibiotic Resistance Database (CARD) is a biological database that collects and organizes reference information on antimicrobial resistance genes, proteins and phenotypes. The database covers all types of drug classes and resistance mechanisms and structures its data based on an ontology. The CARD database was one of the first resources that covered antimicrobial resistance genes. The resource is updated monthly and provides tools to allow users to find potential antibiotic resistance genes in newly-sequenced genomes.
MEGARes is a hand-curated antibiotic resistance database which incorporates previously published resistance sequences for antimicrobial drugs, while also expanding to include published sequences for metal and biocide resistance determinants. In MEGARes 3.0, the nodes of the acyclic hierarchical ontology include four antimicrobial compound types, 59 classes, 223 mechanisms of resistance, and 1,448 gene groups that classify the 8,733 gene accessions. This works in conjunction with the AMR++ bioinformatics pipelin to classify resistome sequences directly from FASTA.
MUBII-TB-DB is a database that focuses on tuberculosis antibiotic resistance genes. It is a highly structured, text-based database focusing on Mycobacterium tuberculosis at seven different mutation loci: rpoB, pncA, katG; mabA(fabG1)-inhA, gyrA, gyrB, and rrs. MUBII analyzes the query using two parallel strategies: 1). A BLAST search against previously mutated sequences. 2). Alignment of query sequences with wild-type sequences. MUBII outputs graphs of alignments and description of the mutation and therapeutic significance. Therapeutically relevant mutations are tagged as "High-Confident" based on the criteria set by Sandgren et al. MUBII-TB-DB provides a platform that is easy to use for even users that are not trained in bioinformatics.
A. C. Matin is an Indian-American microbiologist, immunologist, academician and researcher. He is a professor of microbiology and immunology at Stanford University School of Medicine.
The AMRFinderPlus tool from the National Center for Biotechnology Information (NCBI) is a bioinformatic tool that allows users to identify antimicrobial resistance determinants, stress response, and virulence genes in bacterial genomes. This tool's development began in 2018 and is still underway. The National Institutes of Health funds the development of the software and the databases it uses.
References
- 1 2 3 4 5 Saha, Saurav B; Uttam, Vishwas; Verma, Vivek (2015-05-02). "u-CARE: user-friendly Comprehensive Antibiotic resistance Repository ofEscherichia coli". Journal of Clinical Pathology. 68 (8): 648–651. doi:10.1136/jclinpath-2015-202927. ISSN 0021-9746. PMID 25935546. S2CID 206985362.
- ↑ "AMR Curation". GitHub .