Antibiotic Efflux pumps in Prokaryotic Cells Assignment

1.  The types of membrane transporters are systematically organized in the prokaryotes and also found in eukaryotes with different characteristics, they include 2.A.1 Major Facilitator Super-family, 2.A.6 Resistance Nodulation Division, 2.A.7 Drug metabolite transporters, 2.A.17 Proton-dependent Oligopeptide transporter, 2.A.60 Organo Anion Transporter, 2.A.66 Multidrug Oligosaccharidyl-lipid Polysaccharide Flippase, 2.A.74 Multidrug Endosomal Transporter, 3.A.1 ATP Binding Cassette.
2.  Some of the major physiological mechanisms that the bacteria have developed to elude harmful molecules e.g. antibiotics and chemotherapeutic agents are the efflux pumps. These mechanisms were developed by the bacterial cells to expel toxic molecules found inside the cytosol and inside the cell. Some of these molecules might also include biological molecules. Other mechanisms along this are target modification and production of enzymes to neutralize antibiotics.
3.  The natural function of the membrane transporters is to facilitate the movement of molecules macro and micro molecules. This mostly may include biological molecules such as proteins and also other diffusible molecules that might enter the cell membrane of the bacteria. This is important for the cell to be able to maintain osmotic balance in the cytosol.
4. The major antibiotic transporters found in bacteria are Major Facilitator Super-family, ATP Binding Cassette, Resistance Nodulation Division, Small Multidrug Resistance and Multi-Antimicrobial Extrusion. The drugs acted on are not necessarily structurally or functionally related to each other. Due to the ability of the super-families to recognize different drugs that are not structurally similar, leads to the strain ability to develop cross-resistance that may be the genesis of multi-resistant strains an example P.aeruginosa.
5.  NO.  Different organisms have the capabilities of expressing more than one type of transporter that may be similar to one expressed by another organism. These transporters are known to occur in more than one species. This is because the efflux pumps are known to be located in the bacteria plasmids or transposons and are then spread to other organisms through conjugation.
6. A drug can be recognized by different pumps. An example of the drugs is the tetracycline, fluoroquinolones and chloramphenicols. However those drugs within the same class tend to be more specific in the type of pumps by which they are recognized.
7.  Efflux pumps by themselves are only known to have the ability to give only low or moderate resistance. This is because the natural resistance of many bacterias is dependent on the active systems inducible expression. It is also known that for the efflux pumps to confer high resistance corporation between them and other resistance mechanisms is paramount. An example is resistance in P.aeruginosa whose high resistance is result from combination of, the active efflux system MexAB OprM, the outer membrane barrier and AmpC -lactamase. Further the antibiotics play an important role in the expression of the efflux pump during gene transcription and it s the one that induces the efflux pump.
8. Since genetic characterization has been successfully employed in identifying efflux resistance mechanisms in some bacteria, it has been suggested that genotypic tests be used to identify new effective antimicrobial drugs. Having knowledge of the mechanisms used by these organisms to promote resistance in them, may help in developing new drugs that are not easily susceptible to the efflux pumps of the organisms, thus lowering the probability of resistance to the drugs. This is because the manufactured drugs will be able to minimize over expression of the pumps in the organisms and the development of poor substrate derivatives.
9.  The development of new antibacterial drugs will be dependent on the knowledge of the actions of the pumps on the detection of the different drug molecules. Despite the discovery of pump inhibitors used for therapy, it is important that the new drugs are designed in such a way that they are broad-spectrum inhibitors acting on both gram-negative and gram-positive bacteria of different phylogenetic families to evade rapid developing resistance.


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