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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 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.
A bacteriophage,also known informally as a phage,is a virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν,meaning "to devour". Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome,and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm.
A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular polymeric substances (EPSs). The cells within the biofilm produce the EPS components,which are typically a polymeric conglomeration of extracellular polysaccharides,proteins,lipids and DNA. Because they have three-dimensional structure and represent a community lifestyle for microorganisms,they have been metaphorically described as "cities for microbes".
An antimicrobial is an agent that kills microorganisms (microbicide) or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example,antibiotics are used against bacteria,and antifungals are used against fungi. They can also be classified according to their function. The use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapy,while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.
Antimicrobial peptides (AMPs),also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides. These peptides are potent,broad spectrum antimicrobials which demonstrate potential as novel therapeutic agents. Antimicrobial peptides have been demonstrated to kill Gram negative and Gram positive bacteria,enveloped viruses,fungi and even transformed or cancerous cells. Unlike the majority of conventional antibiotics it appears that antimicrobial peptides frequently destabilize biological membranes,can form transmembrane channels,and may also have the ability to enhance immunity by functioning as immunomodulators.
In microbiology,the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical,usually a drug,which prevents visible in vitro growth of bacteria or fungi. MIC testing is performed in both diagnostic and drug discovery laboratories.
Cathelicidin antimicrobial peptide (CAMP) is a polypeptide that is primarily stored in the lysosomes of macrophages and polymorphonuclear leukocytes (PMNs);in humans,the CAMP gene encodes the peptide precursor CAP-18,which is processed by proteinase 3-mediated extracellular cleavage into the active form LL-37. LL-37 is the only peptide in the Cathelicidin family found in the human body.
Acinetobacter baumannii is a typically short,almost round,rod-shaped (coccobacillus) Gram-negative bacterium. It is named after the bacteriologist Paul Baumann. It can be an opportunistic pathogen in humans,affecting people with compromised immune systems,and is becoming increasingly important as a hospital-derived (nosocomial) infection. While other species of the genus Acinetobacter are often found in soil samples,it is almost exclusively isolated from hospital environments. Although occasionally it has been found in environmental soil and water samples,its natural habitat is still not known.
Polypeptide antibiotics are a chemically diverse class of anti-infective and antitumor antibiotics containing non-protein polypeptide chains. Examples of this class include actinomycin,bacitracin,colistin,and polymyxin B. Actinomycin-D has found use in cancer chemotherapy. Most other polypeptide antibiotics are too toxic for systemic administration,but can safely be administered topically to the skin as an antiseptic for shallow cuts and abrasions.
Persister cells are subpopulations of cells that resist treatment,and become antimicrobial tolerant by changing to a state of dormancy or quiescence. Persister cells in their dormancy do not divide. The tolerance shown in persister cells differs from antimicrobial resistance in that the tolerance is not inherited and is reversible. When treatment has stopped the state of dormancy can be reversed and the cells can reactivate and multiply. Most persister cells are bacterial,and there are also fungal persister cells,yeast persister cells,and cancer persister cells that show tolerance for cancer drugs.
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.
Enzybiotics are an experimental antibacterial therapy first described by Nelson,Loomis,and Fischetti. The term is derived from a combination of the words “enzyme”and “antibiotics.”Enzymes have been extensively utilized for their antibacterial and antimicrobial properties. Proteolytic enzymes called endolysins have demonstrated particular effectiveness in combating a range of bacteria and are the basis for enzybiotic research. Endolysins are derived from bacteriophages and are highly efficient at lysing bacterial cells. Enzybiotics are being researched largely to address the issue of antibiotic resistance,which has allowed for the proliferation of drug-resistant pathogens posing great risk to animal and human health across the globe.
Acyldepsipeptide or cyclic acyldepsipeptide (ADEP) is a class of potential antibiotics first isolated from bacteria and act by deregulating the ClpP protease. Natural ADEPs were originally found as products of aerobic fermentation in Streptomyces hawaiiensis,A54556A and B,and in the culture broth of Streptomyces species,enopeptin A and B. ADEPs are of great interest in drug development due to their antibiotic properties and thus are being modified in attempt to achieve greater antimicrobial activity.
Teixobactin is a peptide-like secondary metabolite of some species of bacteria,that kills some gram-positive bacteria. It appears to belong to a new class of antibiotics,and harms bacteria by binding to lipid II and lipid III,important precursor molecules for forming the cell wall.
NovoBiotic Pharmaceuticals is a privately held,early-stage biotechnology company focused on the discovery and development of new drugs from natural sources.
Eleftheria terrae is a recently discovered Gram-negative bacterium. E. terrae is a temporary name for the organism,as it was only discovered in 2014 and is still undergoing scientific study. It was found to produce a previously unknown antibiotic named teixobactin. The discovery of E. terrae could represent a new age of antibiotics,as teixobactin is the first new antibiotic discovered since the synthetic era of the 1980s. Prior research has indicated that other uncultivable bacteria like E. terrae have potential in the development of new antimicrobial agents.
Enduracididine is a non-proteinogenic α-amino acid that is a cyclic analogue of arginine. It is not genetically encoded into peptide sequences,but rather is generated as a posttranslational modification.
Streptomyces sp. myrophorea,isolate McG1 is a species of Streptomyces,that originates from a (ethnopharmacology) folk cure in the townland of Toneel North in Boho,County Fermanagh. This area was previously occupied by the Druids and before this neolithic people who engraved the nearby Reyfad stones. Streptomyces sp. myrophorea is inhibitory to many species of ESKAPE pathogens,can grow at high pH (10.5) and can tolerate relatively high levels of radioactivity.
Slava Epstein is an American academic,researcher and entrepreneur working in the field of Microbial ecology. He is currently a professor in the biology department of Northeastern University and co-founder of NovoBiotic Pharmaceuticals. As a researcher his most covered contribution is the development of the Isolation chip (iChip) and the discovery of a new antibiotic,Teixobactin. Epstein's research has been published in many leading scientific journals including Nature and Science.
References
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- ↑ "This Solver of Scientific Paradoxes Has Been Named a Fellow of the American Association For the Advancement of Science". 27 November 2018.
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- ↑ Kaeberlein, T.; Lewis, K.; Epstein, S. S. (2002). "Isolating "uncultivable" microorganisms in pure culture in a simulated natural environment". Science. 296 (5570): 1127–1129. doi:10.1126/science.1070633. PMID 12004133. S2CID 28437864.
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- ↑ Shukla, Rhythm; Lavore, Francesca; Maity, Sourav; Derks, Maik G. N.; Jones, Chelsea R.; Vermeulen, Bram J. A.; Melcrová, Adéla; Morris, Michael A.; Becker, Lea Marie; Wang, Xiaoqi; Kumar, Raj; Medeiros-Silva, João; van Beekveld RAM; Bonvin AMJJ; Lorent, Joseph H.; Lelli, Moreno; Nowick, James S.; MacGillavry, Harold D.; Peoples, Aaron J.; Spoering, Amy L.; Ling, Losee L.; Hughes, Dallas E.; Roos, Wouter H.; Breukink, Eefjan; Lewis, Kim; Weingarth, Markus (August 2022). "10.1038/s41586-022-05019-y". Nature. 608 (7922): 390–396. doi:10.1038/s41586-022-05019-y. PMC 9365693 . PMID 35922513.
- ↑ Ling, L. L.; Schneider, T.; Peoples, A. J.; Spoering, A. L.; Engels, I.; Conlon, B. P.; Mueller, A.; Schäberle, T. F.; Hughes, D. E.; Epstein, S.; Jones, M.; Lazarides, L.; Steadman, V. A.; Cohen, D. R.; Felix, C. R.; Fetterman, K. A.; Millett, W. P.; Nitti, A. G.; Zullo, A. M.; Chen, C.; Lewis, K. (2015). "A new antibiotic kills pathogens without detectable resistance". Nature. 517 (7535): 455–459. doi:10.1038/nature14098. PMC 7414797 . PMID 25561178.
- ↑ Imai, Y.; Meyer, K. J.; Iinishi, A.; Favre-Godal, Q.; Green, R.; Manuse, S.; Caboni, M.; Mori, M.; Niles, S.; Ghiglieri, M.; Honrao, C.; Ma, X.; Guo, J. J.; Makriyannis, A.; Linares-Otoya, L.; Böhringer, N.; Wuisan, Z. G.; Kaur, H.; Wu, R.; Mateus, A.; Typas, A.; Savitski, M. M.; Espinoza, J. L.; O'Rourke, A.; Nelson, K. E.; Hiller, S.; Noinaj, N.; Schäberle, T. F.; d'Onofrio, A.; Lewis, K. (2019). "A new antibiotic selectively kills Gram-negative pathogens". Nature. 576 (7787): 459–464. doi:10.1038/s41586-019-1791-1. PMC 7188312 . PMID 31747680.
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- ↑ "Six Northeastern Professors Named to List of Highly Cited Researchers Around The Globe". 9 January 2019.
