A normal strain of microorganism suscepible for a drug, then it produses some protein which helps them for resistance,so how this change occur in molecular level
The strain doesn't develop a new metabolism, it adapts its current metabolism to resist the drug. The usual path for drug resistance is the horizontal transfer of genetics elements giving rise to the resistance of the drug. For instance, the bla gene is responsible for ampicillin resistance. This gene is commonly found on plasmids which can be transferred to other organisms. This transfer is known as horizontal gene transfer and is likely a source of diversification and thus a rise to speciation in the microbiological world.
The strain doesn't develop a new metabolism, it adapts its current metabolism to resist the drug. The usual path for drug resistance is the horizontal transfer of genetics elements giving rise to the resistance of the drug. For instance, the bla gene is responsible for ampicillin resistance. This gene is commonly found on plasmids which can be transferred to other organisms. This transfer is known as horizontal gene transfer and is likely a source of diversification and thus a rise to speciation in the microbiological world.
in fact ,before the drug is applied ,the tolerance already existed in some cells in the colony,but thanks to bottleneck effect ,the cells are too few to prevent drugs from killing most of the microbes. There are various mutations in drug target proteins of microbes and kinds of molecular pumps. As said before ,cells with those weapon are too few but they do exist .In macroscopic view, you may observe that a microbe group gets “new" tolerance ,but in cell scale ,the tolerance is not new.
Yes.plasmid mediated resistance are Higher level resistant types,which replaced the lower level resistant microbial strains-Chromosomal mediated.Transposons often carried on plasmids move from plasmid to plasmid/plasmid to chromosome.Transposons carrying drug resistant genes are highly stable in different species of bacteria ,propagating the genes for single drug resistance or Multi drug resistance.
In addition to horizontal gene transfer, I suggest an influence of accidental mutations, e.g. mistakes during DNA replication. Microorganism can obtain resistance to a drug by less or more possible mutations in 1) the target protein(s), that lower its affinity to the drug, so the drug is no more able to inhibit its activity 2) the ABC transporters (or other pumps) that increase their affinity to the drug so that they can efficiently remove it from the cell 3) some enzymes that deal with a similar compounds, so that mutated enzymes can use this drug as a substrate and inactivate it (e.g. acetylation of some functional groups, or cleavage of some bonds) 4) some enzymes that are involved in synthesis of components of the cell membrane or the cell wall, so that the cell membrane will be more impermeable to the drug.
most of the resistance is because of horizontal gene transfer that is acquiring DNA from out side the cell.. for example Staphylococcus aureus became resistant to vancomycin its because of horizontal gene(Van operon) transfer from Vancomycin resistant Enterococci to Staphylococcus..and also because of shifting of transposons to an active position under that selective pressure also makes the organism resistant to the drug..