Antibióticos: o que são? de onde vêm? como agem? #InstanteBiotec 40

Antibiotics are substances that in low concentrations inhibit the growth and can lead to death of bacteria. Today they may seem ordinary, but antibiotics are so powerful that they are considered the most important discovery for the treatment of infections. They can be naturally produced by other microorganisms such as bacteria and fungi, in order to prevent the growth of other competing bacteria, or they can be a similar product produced entirely or partly by chemical synthesis.

Targets of antibiotics are the physiology and the biochemistry of bacteria. And there are five main targets: the bacterial cell wall, the cell membrane, protein synthesis, DNA and RNA synthesis RNA, and folic acid metabolism. By interfering in any of these processes, antibiotic is threatening the survival of cell.

But no need to worry, these bacterial targets are different or non-existent in eukaryotic cells, such as in human beings, which means that antibiotics are relatively non-toxic drugs to we. β-lactam antibiotics such as penicillins, cephalosporins and carbapenems block the synthesis of the bacterial cell wall. This structure is absent in animal cells, but it is essential for the survival of bacteria The bacterial ribosome is the target of tetracycline, aminoglycosides, macrolides and other antibiotics.

This ribosome is different enough from the eukaryotic ribosome preventing cross-inhibition to occur. In the case of folic acid metabolism, it is present in bacteria but not in humans, whose intake is through the diet. Thus, the antibiotic, such as benzenesulfonamide, that acts in the synthesis of folic acid in bacteria does not have a target on our cells.

Antibiotic resistance, on the other hand, is something to worry about. It is the ability of microorganisms to withstand the effects of an antibiotic or antimicrobial. The inadequate use of antibiotics, either by exacerbated and indiscriminate use in humans, precisely because it does not affect us directly during treatment, or the use in animal diets, promote selective pressure for resistant strains.

Mutations and genetic material sharing followed by selection drive the growth and appearance of strains resistant to many antibiotics. So the story complicates for us, since we have no weapons to fight infection. Bacterial resistance to antibiotics manifested primarily through four mechanisms: the modification of the target; efflux; immunity; and destruction catalyzed by enzymes.

The target modification can occur by mutation of own targets, such as topoisomerases that help unwind the DNA strand during replication. They are the target of fluoroquinolone antibiotics. The antibiotic makes the enzyme to cut DNA more than necessary.

With the mutation in topoisomerase, it becomes less susceptible to bonding with the antibiotic, preventing it to change its function in DNA replication. The target modification can also occur by the production of enzymes that modify antibiotic targets, such as methyltransferase. The bacterial 23S ribosomal RNA is methylated by this enzyme at or near the place where the antibiotic would bind, so he can not bind and interfere in protein synthesis.

Efflux occurs through a large family of protein pumps that expel, among other molecules, antibiotics from the inside of the cell. On immunity, antibiotics or their targets are bound by several proteins preventing antibiotic-target binding. Another mechanism of antibiotic resistance are enzymes that recognize antibiotics and modify them in order to eliminate functional features that allow them to interact with their targets.

The β-lactamases, for example, cleave the β-lactam ring which is characteristic of antibiotics and essential for their action. You must have heard of the antibiotic Vancomycin. It acts by preventing bacteria from forming cell wall by binding to peptides that are required for wall construction, particularly those ending with two copies of the amino acid D-alanine (D-Ala).

But some pathogenic bacteria through horizontal gene transfer, acquired from non-pathogenic vancomycin producing organisms the resistance mechanisms to this molecule. This resistance is a version of target modification, where the resistant bacteria has a new biosynthetic machinery that alters the cell wall structure. They replace one of these D-ala present in the peptide of its cell wall with one D-lactate (D-lac), reducing the vancomycin ability to bind to its target.

Today, this resistance has spread making that dangerous vancomycin-resistant Enterococci (VRE) and Staphyllococcus aureus (VRSA) infections become more common. To solve the problem, American researchers, in 2011, synthesized a new version of vancomycin which binds to peptides with either D-Ala and D-Ala, or D-Ala and D-Lac. Other research groups have made changes in the antibiotic structure to prevent the construction of the bacterial cell wall and to cause its permeability, leading to cell death.

Recently, the researchers who created the new version of the antibiotic in joined these three changes in one vancomycin. The new antibiotic is at least 25,000 times more potent against organisms such as VRE and VRSA. Vancomycin-resistant bacteria were tested with this new version of the antibiotic and even after 50 days adding the antibiotic they were not able to generate resistance, suggesting that the novel compound can be more lasting than current antibiotics.

This new compound is not yet ready for human testing. The researchers want to reduce the number steps necessary for its production and to reduce costs. Then they will test the antibiotics in animals and only then in humans.

This new version of Vancomycin may even be more lasting and more powerful, but we cannot continue to use antibiotics irresponsibly and exaggeratedly. For the emergence of resistance is only one a matter of time. If you liked this video, give a thumbs-up and also share it in your networks.

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