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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 ones which cause the common cold or influenza; drugs which inhibit growth of viruses are termed antiviral drugs or antivirals rather than antibiotics. They are also not effective against fungi; drugs which inhibit growth of fungi are called antifungal drugs.
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.
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.
Vancomycin-resistant Staphylococcus aureus (VRSA) are strains of Staphylococcus aureus that have acquired resistance to the glycopeptide antibiotic vancomycin. Bacteria can acquire resistant genes either by random mutation or through the transfer of DNA from one bacterium to another. Resistance genes interfere with the normal antibiotic function and allow a bacteria to grow in the presence of the antibiotic. Resistance in VRSA is conferred by the plasmid-mediated vanA gene and operon. Although VRSA infections are uncommon, VRSA is often resistant to other types of antibiotics and a potential threat to public health because treatment options are limited. VRSA is resistant to many of the standard drugs used to treat S. aureus infections. Furthermore, resistance can be transferred from one bacterium to another.
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.
Lincosamides are a class of antibiotics, which include lincomycin, clindamycin, and pirlimycin.
Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of Streptomyces bacteria or produced semi-synthetically from those isolated compounds. Tetracycline molecules comprise a linear fused tetracyclic nucleus to which a variety of functional groups are attached. Tetracyclines are named after their four ("tetra-") hydrocarbon rings ("-cycl-") derivation ("-ine"). They are defined as a subclass of polyketides, having an octahydrotetracene-2-carboxamide skeleton and are known as derivatives of polycyclic naphthacene carboxamide. While all tetracyclines have a common structure, they differ from each other by the presence of chloro, methyl, and hydroxyl groups. These modifications do not change their broad antibacterial activity, but do affect pharmacological properties such as half-life and binding to proteins in serum.
In microbiology, efflux is the moving of a variety of different compounds out of cells, such as antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters. All microorganisms, with a few exceptions, have highly conserved DNA sequences in their genome that encode efflux pumps. Efflux pumps actively move substances out of a microorganism, in a process known as active efflux, which is a vital part of xenobiotic metabolism. This active efflux mechanism is responsible for various types of resistance to bacterial pathogens within bacterial species - the most concerning being antibiotic resistance because microorganisms can have adapted efflux pumps to divert toxins out of the cytoplasm and into extracellular media.
Hygromycin B is an antibiotic produced by the bacterium Streptomyces hygroscopicus. It is an aminoglycoside that kills bacteria, fungi and higher eukaryotic cells by inhibiting protein synthesis.
The resistome has been used to describe to two similar yet separate concepts:
Functional cloning is a molecular cloning technique that relies on prior knowledge of the encoded protein’s sequence or function for gene identification. In this assay, a genomic or cDNA library is screened to identify the genetic sequence of a protein of interest. Expression cDNA libraries may be screened with antibodies specific for the protein of interest or may rely on selection via the protein function. Historically, the amino acid sequence of a protein was used to prepare degenerate oligonucleotides which were then probed against the library to identify the gene encoding the protein of interest. Once candidate clones carrying the gene of interest are identified, they are sequenced and their identity is confirmed. This method of cloning allows researchers to screen entire genomes without prior knowledge of the location of the gene or the genetic sequence.
mecA is a gene found in bacterial cells which allows them to be resistant to antibiotics such as methicillin, penicillin and other penicillin-like antibiotics.
Microbiota are the range of microorganisms that may be commensal, mutualistic, or pathogenic found in and on all multicellular organisms, including plants. Microbiota include bacteria, archaea, protists, fungi, and viruses, and have been found to be crucial for immunologic, hormonal, and metabolic homeostasis of their host.
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.
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.
FARME also known as Functional Antibiotic Resistance Metagenomic Element is a database that compiles publicly available DNA elements and predicted proteins that confer antibiotic resistance, regulatory elements and mobile genetic elements. It is the first database to focus on functional metagenomics. This allows the database to understand 99% of bacteria which cannot be cultured, the relationship between environmental antibiotic resistance sequences and antibiotic genes derived from cultured isolates. This information was derived from 20 metagenomics projects from GenBank. Also from GenBank are the protein sequence predictions and annotations.
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.
Clinical metagenomic next-generation sequencing (mNGS) is the comprehensive analysis of microbial and host genetic material in clinical samples from patients by next-generation sequencing. It uses the techniques of metagenomics to identify and characterize the genome of bacteria, fungi, parasites, and viruses without the need for a prior knowledge of a specific pathogen directly from clinical specimens. The capacity to detect all the potential pathogens in a sample makes metagenomic next generation sequencing a potent tool in the diagnosis of infectious disease especially when other more directed assays, such as PCR, fail. Its limitations include clinical utility, laboratory validity, sense and sensitivity, cost and regulatory considerations.
Karen Bush is an American biochemist. She is a professor of Practice in Biology at Indiana University and the interim director of the Biotechnology program. Bush conducts research focusing on bacterial resistance mechanisms to beta-lactam antibiotics.
Multidrug-resistant bacteria are bacteria that are resistant to three or more classes of antimicrobial drugs. MDR bacteria have seen an increase in prevalence in recent years and pose serious risks to public health. MDR bacteria can be broken into 3 main categories: Gram-positive, Gram-negative, and other (acid-stain). These bacteria employ various adaptations to avoid or mitigate the damage done by antimicrobials. With increased access to modern medicine there has been a sharp increase in the amount of antibiotics consumed. Given the abundant use of antibiotics there has been a considerable increase in the evolution of antimicrobial resistance factors, now outpacing the development of new antibiotics.
References
- ↑ Ehrlich, S. Dusko; Kennedy, Sean P.; Doré, Joël; Haimet, Florence; Weiszer, Kevin; Levenez, Florence; Letur, Aline; Léjard, Véronique; Léonard, Pierre (January 2019). "Prediction of the intestinal resistome by a three-dimensional structure-based method" (PDF). Nature Microbiology. 4 (1): 112–123. doi: 10.1038/s41564-018-0292-6 . ISSN 2058-5276. PMID 30478291. S2CID 53757858.
- ↑ Zankari, E.; Hasman, H.; Cosentino, S.; Vestergaard, M.; Rasmussen, S.; Lund, O.; Aarestrup, F. M.; Larsen, M. V. (2012-07-10). "Identification of acquired antimicrobial resistance genes". Journal of Antimicrobial Chemotherapy. 67 (11): 2640–2644. doi:10.1093/jac/dks261. ISSN 0305-7453. PMC 3468078 . PMID 22782487.
- ↑ Gupta, Sushim Kumar; Padmanabhan, Babu Roshan; Diene, Seydina M.; Lopez-Rojas, Rafael; Kempf, Marie; Landraud, Luce; Rolain, Jean-Marc (2013-10-21). "ARG-ANNOT, a New Bioinformatic Tool To Discover Antibiotic Resistance Genes in Bacterial Genomes". Antimicrobial Agents and Chemotherapy. 58 (1): 212–220. doi:10.1128/aac.01310-13. ISSN 0066-4804. PMC 3910750 . PMID 24145532.
- ↑ "RED-DB" . Retrieved July 27, 2019.
- ↑ "Marilyn Roberts website".
- ↑ Allen, Heather K; Moe, Luke A; Rodbumrer, Jitsupang; Gaarder, Andra; Handelsman, Jo (2008-10-09). "Functional metagenomics reveals diverse β-lactamases in a remote Alaskan soil". The ISME Journal. 3 (2): 243–251. doi: 10.1038/ismej.2008.86 . ISSN 1751-7362. PMID 18843302. S2CID 16496336.
- ↑ Moore, Aimée M.; Patel, Sanket; Forsberg, Kevin J.; Wang, Bin; Bentley, Gayle; Razia, Yasmin; Qin, Xuan; Tarr, Phillip I.; Dantas, Gautam (2013-11-13). "Pediatric Fecal Microbiota Harbor Diverse and Novel Antibiotic Resistance Genes". PLOS ONE. 8 (11): e78822. Bibcode:2013PLoSO...878822M. doi: 10.1371/journal.pone.0078822 . ISSN 1932-6203. PMC 3827270 . PMID 24236055.
- ↑ Sommer, M. O. A.; Dantas, G.; Church, G. M. (2009-08-27). "Functional Characterization of the Antibiotic Resistance Reservoir in the Human Microflora". Science. 325 (5944): 1128–1131. Bibcode:2009Sci...325.1128S. doi:10.1126/science.1176950. ISSN 0036-8075. PMC 4720503 . PMID 19713526.
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