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An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics.
Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. Antibiotic resistance is a subset of AMR, that applies specifically to bacteria that become resistant to antibiotics.
Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is, resistance has evolved. Antimicrobial resistance and antineoplastic resistance challenge clinical care and drive research. When an organism is resistant to more than one drug, it is said to be multidrug-resistant.
Pseudomonas is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 validly described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a wide range of niches. Their ease of culture in vitro and availability of an increasing number of Pseudomonas strain genome sequences has made the genus an excellent focus for scientific research; the best studied species include P. aeruginosa in its role as an opportunistic human pathogen, the plant pathogen P. syringae, the soil bacterium P. putida, and the plant growth-promoting P. fluorescens, P. lini, P. migulae, and P. graminis.
Pseudomonas fluorescens is a common Gram-negative, rod-shaped bacterium. It belongs to the Pseudomonas genus; 16S rRNA analysis as well as phylogenomic analysis has placed P. fluorescens in the P. fluorescens group within the genus, to which it lends its name.
Mupirocin, sold under the brand name Bactroban among others, is a topical antibiotic useful against superficial skin infections such as impetigo or folliculitis. It may also be used to get rid of methicillin-resistant S. aureus (MRSA) when present in the nose without symptoms. Due to concerns of developing resistance, use for greater than ten days is not recommended. It is used as a cream or ointment applied to the skin.
The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium Amycolatopsis rifamycinica or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective against mycobacteria, and are therefore used to treat tuberculosis, leprosy, and mycobacterium avium complex (MAC) infections.
Kanamycin A, often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. It is not a first line treatment. It is used by mouth, injection into a vein, or injection into a muscle. Kanamycin is recommended for short-term use only, usually from 7 to 10 days. As with most antibiotics, it is ineffective in viral infections.
Pseudomonas aeruginosa is a common encapsulated, Gram-negative, strict aerobic, roundly-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, P. aeruginosa is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes.
Viomycin is a member of the tuberactinomycin family, a group of nonribosomal peptide antibiotics exhibiting anti-tuberculosis activity. The tuberactinomycin family is an essential component in the drug cocktail currently used to fight infections of Mycobacterium tuberculosis. Viomycin was the first member of the tuberactinomycins to be isolated and identified, and was used to treat TB until it was replaced by the less toxic, but structurally related compound, capreomycin. The tuberactinomycins target bacterial ribosomes, binding RNA and disrupting bacterial protein synthesis and certain forms of RNA splicing. Viomycin is produced by the actinomycete Streptomyces puniceus.
Antibiotic sensitivity testing or antibiotic susceptibility testing is the measurement of the susceptibility of bacteria to antibiotics. It is used because bacteria may have resistance to some antibiotics. Sensitivity testing results can allow a clinician to change the choice of antibiotics from empiric therapy, which is when an antibiotic is selected based on clinical suspicion about the site of an infection and common causative bacteria, to directed therapy, in which the choice of antibiotic is based on knowledge of the organism and its sensitivities.
COMBREX is a multifaceted project that includes a database of gene annotations, functional predictions and recommendations based on Active Learning principles associated with millions of genes in prokaryotic genomes.
The Consensus Coding Sequence (CCDS) Project is a collaborative effort to maintain a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assemblies. The CCDS project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier, and ensures that they are consistently represented by the National Center for Biotechnology Information (NCBI), Ensembl, and UCSC Genome Browser. The integrity of the CCDS dataset is maintained through stringent quality assurance testing and on-going manual curation.
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 2.0, the nodes of the acyclic hierarchical ontology include four antimicrobial compound types, 57 classes, 220 mechanisms of resistance, and 1,345 gene groups that classify the 7,868 accessions. This works in conjunction with the AmrPlusPlus pipeline to classify resistome sequences directly from FASTA.
Mustard is a database that tracks Antimicrobial Resistance Determinants (ARDs). The method by which it tracks ARDs is using their own method adapted from Protein Homology Modelling called Pairwise Comparative Modelling (PCM), which increase specificity protein prediction, especially for distantly related protein homologues. Using PCM, 6095 ARDs from 20 families in the human gut microbiota. Antibiotic resistance databases used were ResFinder, ARG-ANNOT, the now defunct Lahey Clinic, Marilyn Roberts website for tetracycline and macrolide resistance genes and metagenomics.
RAC otherwise known as Repository of Antibiotic resistance Cassettes is a database that uses the automatic Attacca annotation system in order to comprehensively annotate gene-cassettes and transposable elements in a stream-lined manner and to discover novel gene cassettes. Antibiotic resistance is often due to horizontal gene transfer, which allows resistance to arise through cell-to-cell interaction. This poses a major challenge in the field of antibiotic resistance. Hence, the creation of RAC which would provide researchers a comprehensive and unique tool for the endeavor of documenting resistance due to gene-cassettes and transposable elements. Attacca helps discover novel gene cassettes when any three of the following occurs as mentioned in Tsafnat et al, 2011:
The SARG database also known as Structured Antibiotic Resistance Gene database is a collection of antimicrobial resistance genes. The hierarchical structure of the database is clear to be 1) Type: antibiotic type 2) Subtype: genotype 3) Sequence: reference sequence. The SARG database helps in quick survey of antimicrobial resistance genes from environmental samples. The database was initially integrated from ARDB and Comprehensive Antibiotic Resistance Database, followed by hand curation including removing non-ARG sequences, removing redundant sequences and SNP sequences. Other sources include NCBI nr database and published papers.
Biocuration is the field of life sciences dedicated to organizing biomedical data, information and knowledge into structured formats, such as spreadsheets, tables and knowledge graphs. The biocuration of biomedical knowledge is made possible by the cooperative work of biocurators, software developers and bioinformaticians and is at the base of the work of biological databases.
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 Zhang, L.; Vikesland, P. J.; Pruden, A.; Heath, L. S.; Riquelme, M. V.; Garner, E.; Guron, G. K. P.; Arango-Argoty, G. A. (2019-03-06). "ARGminer: A web platform for crowdsourcing-based curation of antibiotic resistance genes". bioRxiv: 274282. doi: 10.1101/274282 .