Sunday, May 12, 2013

antibiotic

An antibacterial is an agent that inhibits bacterial growth or kills bacteria. The term is often used synonymously with the term antibiotic(s). Today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic(s) has come to denote a broader range of antimicrobial compounds, including anti-fungal and other compounds.

The term antibiotic was first used in 1942 by Selman Waksman and his collaborators in journal articles to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution. This definition excluded substances that kill bacteria, but are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the sulfonamides. Many antibacterial compounds are relatively small molecules with a molecular weight of less than 2000 atomic units.

With advances in medicinal chemistry, most of today's antibacterials chemically are semisynthetic modifications of various natural compounds. Compounds that are still isolated from living organisms are the aminoglycosides, whereas other antibacterials -- for example, the sulfonamides, the quinolones, and the oxazolidinones -- are produced solely by chemical synthesis. In accordance with this, many antibacterial compounds are classified on the basis of chemical/biosynthetic origin into natural, semisynthetic, and synthetic. Another classification system is based on biological activity; in this classification, antibacterials are divided into two broad groups according to their biological effect on microorganisms: bactericidal agents kill bacteria, and bacteriostatic agents slow down or stall bacterial growth.

Antibiotic resistance is a form of drug resistance whereby some (or, less commonly, all) sub-populations of a microorganism, is usually a bacterial species, are able to survive after exposure to one or more antibiotics; pathogens resistant to multiple antibiotics are considered multidrug resistant (MDR) or, more colloquially, superbugs.

Antibiotic resistance is a serious and growing phenomenon in contemporary medicine and has emerged as one of the pre-eminent public health concerns of the 21st century, particularly as it pertains to pathogenic organisms (the term is especially relevant to organisms which cause disease in humans). In the simplest cases, drug-resistant organisms may have acquired resistance to first-line antibiotics, thereby necessitating the use of second-line agents. Typically, a first-line agent is selected on the basis of several factors including safety, availability and cost; a second-line agent is usually broader in spectrum, has a less favorable risk-benefit profile and is more expensive or, in dire circumstances, is locally unavailable.

It may take the form of a spontaneous or induced genetic mutation, or the acquisition of resistance genes from other bacterial species by horizontal gene transfer via conjugation, transduction, or transformation. Many antibiotic resistance genes reside on transmissible plasmids, facilitating their transfer. Exposure to an antibiotic naturally selects for the survival of the organisms with the genes for resistance. In this way, a gene for antibiotic resistance may readily spread through an ecosystem of bacteria. Antibiotic-resistance plasmids frequently contain genes conferring resistance to several different antibiotics.

Genes for resistance to antibiotics, like the antibiotics themselves, are ancient. However, the increasing prevalence of antibiotic-resistant bacterial infections seen in clinical practice stems from antibiotic use both within human medicine and veterinary medicine. Any use of antibiotics can increase selective pressure in a population of bacteria to allow the resistant bacteria to thrive and the susceptible bacteria to die off. As resistance towards antibiotics becomes more common, a greater need for alternative treatments arises. However, despite a push for new antibiotic therapies there has been a continued decline in the number of newly approved drugs. Antibiotic resistance therefore poses a significant problem.

Plasmid
A plasmid is a small DNA molecule that is physically separate from, and can replicate independently of, chromosomal DNA within a cell. Most commonly found as small circular, double stranded DNA molecules in bacteria, plasmids are sometimes present in archaea and eukaryotic organisms. In nature, plasmids carry genes that may benefit survival of the organism (e.g. antibiotic resistance), and can frequently be transmitted from one bacterium to another (even of another species) via horizontal gene transfer.

Plasmid sizes vary from 1 to 1000 kilo base pairs (kbp). The number of identical plasmids in a single cell can range anywhere from one to thousands under some circumstances. Plasmids can be considered part of the mobilome because they are often associated with conjugation, a mechanism of horizontal gene transfer.

Plasmid host-to-host transfer requires direct mechanical transfer by conjugation, or changes in incipient host gene expression allowing the intentional uptake of the genetic element by transformation. Plasmids provide a mechanism for horizontal gene transfer within a population of microbes and typically provide a selective advantage under a given environmental state. Plasmids may carry genes that provide resistance to naturally occurring antibiotics in a competitive environmental niche, or the proteins produced may act as toxins under similar circumstances.

Sources:

http://en.wikipedia.org/wiki/Antibacterial
http://en.wikipedia.org/wiki/Antibiotic_resistance
http://en.wikipedia.org/wiki/Plasmid

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