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фильм долгая дорога домой смотреть онлайн все серии, Mechanisms of Antibiotic Resistance - PMC, Understanding Bacterial Resistance Mechanisms, How do bacteria actually become resistant to antibiotics?, Resistance mechanisms – Antibiotic resistance – ReAct, Bacterial defences: mechanisms, evolution and antimicrobial - Nature, Overview of antimicrobial resistance and mechanisms: The relative , How do antibiotics work, and how does antibiotic resistance evolve .
One of the best characterized examples of resistance through enzymatic modification of the target site is the methylation of the ribosome catalyzed by an enzyme encoded by the erm genes (erythromycin ribosomal methylation), which results in macrolide resistance. These enzymes are capable of mono- or dimethylating an adenine residue in position A2058 of the domain V of the 23rRNA of the 50S ribosomal subunit. Due to this biochemical change, the binding of the antimicrobial molecule to its target is impaired. Importantly, since macrolides, lincosamides, and streptogramin B antibiotics have overlapping binding sites in the 23S rRNA, expression of the erm genes confers cross-resistance to all members of the MLSB group (, ). More than 30 different erm genes have been described, many of them located in MGEs, which may account for their ample distribution among different genera, including aerobic and anaerobic gram-positive and gram-negative bacteria. In staphylococci, the most important erm genes are ermA (mostly distributed in a transposon in MRSA) and erm(C) (found in plasmids in methicillin-susceptible S. aureus). On the other hand, erm(B) has been more frequently reported in enterococci and pneumococci (where it was first described), located in plasmids and conjugative and non-conjugative transposons such as Tn917 and Tn551. Importantly, these genes are widely distributed and have now been found in over 30 different bacterial genera (). Erm-mediated resistance carries an important bacterial fitness cost due to less efficient translation by the methylated ribosome. Hence, although the MLSB phenotype can be constitutively expressed, in most cases it is subject to strict control via a complex posttranscriptional gene regulation. Through this mechanism, bacteria growing in the absence of antibiotics produce an inactive mRNA transcript that cannot be translated into the desired protein (in this case a methylase). Conversely, in the presence of antibiotic, the transcript becomes active and the system is primed to confer rapid resistance. This is best characterized by the inducible MLSB phenotype of the erm(C) operon in S. aureus, which is conformed by the erm(C) gene, an upstream gene encoding a leader peptide and an intergenic region (). In the absence of an inducer, transcription of the operon generates an mRNA with a secondary structure that conceals the ribosomal binding site upstream of erm. Translation proceeds through the leader peptide, then terminates, preventing the production of ErmC. In the presence erythromycin (but also other macrolides), the ribosome stalls due to inhibition by the antibiotic during translation of the leader peptide allowing a conformational change in the ermC mRNA that unmasks its ribosomal binding site, resulting in efficient translation of erm(C) (). Thus, bacteria have evolved a sophisticated mRNA-based control mechanism to tightly regulate the expression of these methylases, ensuring a high efficiency of action in the presence of the antibiotic while minimizing the fitness costs for the bacterial population. The array of compounds capable of inducing the MLSB phenotype varies among different erm genes, but as a general rule the best inducer is erythromycin while the inducing ability of other macrolides varies. Similarly, the system is usually not induced by lincosamides or streptogramins. However, the use of these agents against isolates carrying inducible erm genes may result in the selection of constitutive mutants in vivo (particularly in severe infections) leading to therapeutic failures., A complete understanding of the mechanisms by which bacteria become resistant to antibiotics is of paramount importance to design novel strategies to counter the resistance threat., One of the most common methods bacteria use to evade antibiotics is to alter the drug’s target. Most antibiotics work by binding to specific proteins or structures within the bacterial cell—such as the ribosome, cell wall, or DNA enzymes..
Antimicrobial resistance is one of the biggest global threats to health, food security and development. Here are the four ways in which bacteria have learnt to adapt and become resistant., As a consequence, bacteria have developed many resistance mechanisms to withstand the actions of antibiotics. There are two main ways for bacteria to withstand the effects of an antibiotic: By preventing the antibiotic from reaching its intended target at a high concentration. By modifying or bypassing the target on which the antibiotic acts., Many defences offer broad protection against various threats, which means that bacteria often have preadaptations that potentiate resistance to antimicrobials in the clinic., Resistant drug uptake, target site change, efflux pump mechanism, and target site mutation are examples of resistance mechanisms. The presence of resistant bacteria and antibiotic residues in the environment requires urgent global action to combat antimicrobial resistance (AMR)., Different classes of antibiotics target different features of bacteria, as the diagram below shows. For example, beta-lactam antibiotics, like penicillin, block the production of the “peptidoglycan layer”, a key component of bacterial cell walls. This weakens the wall, causing the bacteria to burst.2., Bacteria have evolved numerous mechanisms to survive antibiotic exposure. These resistance mechanisms can be intrinsic (inherent to the bacterial species) or acquired through genetic changes. Bacteria produce enzymes that modify or degrade antibiotics, rendering them ineffective..