An antimicrobial is a substance that kills or inhibits the growth of microorganisms bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes (microbiocidal) or prevent the growth of microbes (microbiostatic). Disinfectants are antimicrobial substances used on non-living objects or outside the body.
A cluster of Escherichia coli Bacteria magnified 10,000 times.
A cluster of Escherichia coli Bacteria magnified 10,000 times.
The discovery of antimicrobials, like penicillin and tetracycline, paved the way for better health for millions of people around the world. Before penicillin became a viable medical treatment in the early 1940's, no true cure for gonorrhea, strep throat, or pneumonia existed. Patients with infected wounds often had to have a wounded limb removed or face death from infection. Now, most of these infections can be cured easily with a short course of antimicrobials.
However, with the development of antimicrobials, microorganisms have adapted and become resistant to previous antimicrobial agents. The old antimicrobial technology was based either on poisons or heavy metals, which may not have killed the microbe completely. This allowed the microbe to survive, change, and become resistant to the poisons and/or heavy metals.
Antimicrobial nanotechnology is a recent addition to the fight against disease causing organisms. It replaces heavy metals and toxins and may someday be a viable alternative.
Infections that are acquired during a hospital visit are called "hospital acquired infections" or nosocomial infections. Similarly, when the infectious disease is picked up in the non-hospital setting it is considered "community acquired. "
There are mainly two classes of antimicrobial drugs: those obtained from natural sources (i.e. beta-lactam) antibiotic (such as penicillins, cephalosporins) or protein synthesis inhibitors (such as aminoglycosides, macrolides, tetracyclines, chloramphenicol, polypeptides); and synthetic agents.
A β-lactam (beta-lactam) ring is a four-membered lactam. A lactam is a cyclic amide. It is named as such, because the nitrogen atom is attached to the β-carbon relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone.
A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. While a broad interpretation of this definition could be used to describe nearly any antibiotic, in practice, it usually refers to substances that act at the ribosome level (either the ribosome itself or the translation factor), taking advantage of the major differences between prokaryotic and eukaryotic ribosome structures. Toxins such as ricin also function via protein synthesis inhibition. Ricin acts at the eukaryotic 60S.
In general, protein synthesis inhibitors work at different stages of prokaryotic mRNA translation into proteins, like initiation, elongation (including aminoacyl tRNA entry, proofreading, peptidyl transfer, and ribosomal translocation), and termination. Rifamycin inhibits prokaryotic DNA transcription into mRNA by inhibiting DNA-dependent RNA polymerase by binding its beta-subunit. Linezolid acts at the initiation stage probably by preventing the formation of the initiation complex, although the mechanism is not fully understood.
Tetracyclines and Tigecycline (a glycylcycline related to tetracyclines) block the A site on the ribosome, preventing the binding of aminoacyl tRNAs. Aminoglycosides, among other potential mechanisms of action, interfere with the proofreading process, causing increased rate of error in synthesis with premature termination. Chloramphenicol blocks the peptidyl transfer step of elongation on the 50S ribosomal subunit in both bacteria and mitochondria. Macrolides (as well as inhibiting ribosomal translocation and other potential mechanisms) bind to the 50s ribosomal subunits, inhibiting peptidyl transfer. Quinupristin/dalfopristin act synergistically, with dalfopristin, enhancing the binding of quinupristin as well as inhibiting peptidyl transfer. Quinupristin binds to a nearby site on the 50S ribosomal subunit and prevents elongation of the polypeptide. It also causes incomplete chains to be released. Macrolides, clindamycin, and aminoglycosides (with all these three having other potential mechanisms of action as well) have evidence of inhibition of ribosomal translocation. Fusidic acid prevents the turnover of elongation factor G (EF-G) from the ribosome. Macrolides and clindamycin (both also having other potential mechanisms) cause premature dissociation of the peptidyl-tRNA from the ribosome. Puromycin has a structure similar to that of the tyrosinyl aminoacyl-tRNA. Therefore, it binds to the ribosomal A site and participates in peptide bond formation, producing peptidyl-puromycin. However, it does not engage in translocation and quickly dissociates from the ribosome, causing a premature termination of polypeptide synthesis.