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JF-Expert Member
- Nov 28, 2012
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DRUG RESISTANCE
A. Plasmid-this is an extra chromosomal DNA genetically material that are mostly found in microbes i.e. bacteria. they are small loops of DNA which is double stranded .Used to exchange DNA between bacteria cells They contains genes giving resistance to antibiotics The plasmid is not their essential for normal life and function of the host bacteria but it may confer on it drug resistance, bacteriocin,production, toxigenicity e.t.c Plasmid contains 50-100 genes .Plasmid DNA may get integrated into host cell genome, in this state it is often known as episode. But both these terms are frequently used synomously. Some plasmid confer on host cell maleness or ability to conjugate(bacteria equivalent of sexual mating in higher organism). Following to the recipient acquire the plasmid and it turns becomes maleness is known F plasmid codes for production of sex pilus trough which it establish contact with the recipient bacterium and transfer a copy of F plasmid into recipient. Such plasmid contains information for self transfer to another cell by conjugation is known as conjugative or self transmissible plasmid . Those plasmid which do not posses information for self transfer to another cell are known as non conjugative or non self transmissible plasmid. However this can be transferred with the help of transfer factor such as colicn plasmid (Co1 I) and through the agency of bacteriophages (transduction). B.Why they are getting resistance against antibiotics? Antibiotics -this is a substance produced by the natural metabolic processes of some microorganism that can inhibit or destroy other microorganism . example penicillin produced from penicillium is destroy the cell wall of bacteria . Antibiotic resistance many plamid mediated resistance involve extracellular inactivation of the drug by enzymatic modification or degradation of its element . Example B- lactamases of plasmid found in bacteria destroy the B lactam of penicillin and cephalosporins . Mechanism of drug action The overall useful target of the drug are mainly five which are 1.Inbihition of the cell wall synthesis e.g. Penicillin and cephalosporins. 2.breakdown of the cell membrane structure or structure of function e.g. polymixins and polyene 3.Inhibition of structure and function of DNA and RNA e.g. chloroquine and AZT 4. Inhibition of protein synthesis e.g. Oxazolidinones 5. Brocks on key metabolic pathways e.g. Sulfonamides How do these antibiotic act and how resistance occur 1. Cell wall The beta-lactam group of antibiotic (penicillin) they affect cell wall of bacteria. How- cell wall of most bacteria contains a rigid girdle of peptidoglycan, which protect the cell from rupture from hypotonic environment. Active cells must constantly synthesize new peptidoglycan and transport it to its proper in the cell envelope so the penicillin and cephalosporins react with one or more of the enzyme required to complete this process, causing cell to develop weak point at growth sites and to becomes osmotically fragile hence lysis . Note; antibiotics are active only in young and growing cell because old, inactive, or dormant cell do not synthesize peptidoglycan. Action; penicillin and cephalosporins bind and block peptidase that cross links the glycan molecule , there by interrupting the completion of the cell wall. How resistance occur-The bacteria produce beta lactamase or penicilliase enzyme that that bind with beta lactam(active site ) of the penicillin and destroy it hence cillin will no longer active again. 2.Cell membranes The antibiotics that damage cell membrane they have specificity for microbial groups based on differences of their cell membranes. Action-the antibiotics polymyxins from bacillus polymyxa it is usually interact with membrane phospholipids and cause leakage of proteins and nitrogen bases. How resistance occur- the receptor that transport the drug toward the cell is altered, hence new receptor is formed hence the antibiotic will fail to bind with the receptor sites of the cell membrane. 3.NUCLEIC ACIDS The antibiotics like fluoroquinolones that are chemically related to quinine , they are mostly affect the bacteria DNA, Action- the antibiotics fluoroquinolones they affect bacteria by binding to DNA gyrase and related enzyme topoisomerase iv hence the DNA replication of the bacteria will fail, but the antibiotic rifampin which is essential for tuberculosis for this his primary action is blocking action of RNA polymerase hence preventing transcription, How resistance occur- The microbes they activate the specialized membrane of proteins and continually pump the drug out of the cell. 4.INHIBITION OF PROTEIN SYNTHESIS. In bacteria cell there is specialized organelles that is responsible in protein synthesis and these are ribosome. Action of antibiotics to microbes ribosome -The antibiotics like aminoglyicoside sthat have one or more amino sugars and an aminocyclitol they affect the synthesis of protein synthesis in ribosome by binding to one of ribosomal sub units hence the protein synthesis will be failed. How resistance occur-the bacteria of microbes can become resistant to amino glycosides when point in ribosomal proteins arise and not only that the microbes is associated with the alteration or 50s ribosomal binding site. 5.BLOCKS ON KEY METABOLLIC PATTERNS The drug like sulfonamides or sulfa drugs they do function as metabolic analog to block synthesis of folic acid by bacteria. Action of antibiotics-the sulfa drug they do function as metabolic analog since they block the synthesis of folic acid by bacteria hence no metabolic will run anymore. How resistance occur-the action antimetabolities can be circumvented if a microbe develop and alternative metabolic pathway or enzyme . Sulfonamides and trimethoprim resistance develops when microbes deviate from the usual patterns of folic acid but fung can acquire resistance to flucytosine by completely shutting off certain metabolic activities. QN,C. HOW TO PREVENT ANTIBIOTICS RESISTANCE SPREAD IN MICROBES. There are ways that if they could be used properly the spread of antibiotics resistance in microbes will be prevented and these are. General principle for use of antibiotics 1.Physicians have the responsibility for making an accurate diagnosis and prescribing the correct drug therapy. Hence he/she could make the correct diagnosis , find the site of infection and organisms responsible than use antibioagent after finding the sensitivity. 2.Remove barrier e.g. Lack of free drainage of abscesses(so drain the abscess before starting antibiotics) 4.Select the best drug i.e. Activity of the drug should match with the infecting organism .The drug should be capable of reaching the site of infection. 5.Patients must comply with and careful follow the physicians guidelines. It is important for the patient to take the correct dosage , by the best route , for appropriate period. This diminishes the selection for mutants that can resists low drug levels, and ensure elimination of the pathogens. 6.Therapy should continued till apparent cure is achieved and three days more to avoid relapse. 7.In typhoid , tuberculosis and endocardits the drug should be continued for a longer time after apparent clinical cure. 8.Combined therapy is administration of two or more drugs together and increase that at least one of the drugs will be effective and that a resistant strain of either drug will not be able to persist. The success depends on carefully choosing drugs that have different metabolic targets .it is unlikely a microbe would posses resistance to multiple drugs with distinct target. 9.Microbiological examination to be done ;to prove the complete cure after withdrawal of antibiotics agent this helps to prevent the rise of antibiotics resistance in case where the microbes wont be diminishes. 10. Prophylactic chemo therapy for surgical and dental procedure should start at the time of surgery and continue for 48 hours to reduce the risk of development of antibiotics resistance. hydrogen peroxide, mouthwash. The antiseptic they mostly used in a body skin living tissue which they do help to remove microbes from the body skin. .................... CHAGUO NI LAKO........................
A. Plasmid-this is an extra chromosomal DNA genetically material that are mostly found in microbes i.e. bacteria. they are small loops of DNA which is double stranded .Used to exchange DNA between bacteria cells They contains genes giving resistance to antibiotics The plasmid is not their essential for normal life and function of the host bacteria but it may confer on it drug resistance, bacteriocin,production, toxigenicity e.t.c Plasmid contains 50-100 genes .Plasmid DNA may get integrated into host cell genome, in this state it is often known as episode. But both these terms are frequently used synomously. Some plasmid confer on host cell maleness or ability to conjugate(bacteria equivalent of sexual mating in higher organism). Following to the recipient acquire the plasmid and it turns becomes maleness is known F plasmid codes for production of sex pilus trough which it establish contact with the recipient bacterium and transfer a copy of F plasmid into recipient. Such plasmid contains information for self transfer to another cell by conjugation is known as conjugative or self transmissible plasmid . Those plasmid which do not posses information for self transfer to another cell are known as non conjugative or non self transmissible plasmid. However this can be transferred with the help of transfer factor such as colicn plasmid (Co1 I) and through the agency of bacteriophages (transduction). B.Why they are getting resistance against antibiotics? Antibiotics -this is a substance produced by the natural metabolic processes of some microorganism that can inhibit or destroy other microorganism . example penicillin produced from penicillium is destroy the cell wall of bacteria . Antibiotic resistance many plamid mediated resistance involve extracellular inactivation of the drug by enzymatic modification or degradation of its element . Example B- lactamases of plasmid found in bacteria destroy the B lactam of penicillin and cephalosporins . Mechanism of drug action The overall useful target of the drug are mainly five which are 1.Inbihition of the cell wall synthesis e.g. Penicillin and cephalosporins. 2.breakdown of the cell membrane structure or structure of function e.g. polymixins and polyene 3.Inhibition of structure and function of DNA and RNA e.g. chloroquine and AZT 4. Inhibition of protein synthesis e.g. Oxazolidinones 5. Brocks on key metabolic pathways e.g. Sulfonamides How do these antibiotic act and how resistance occur 1. Cell wall The beta-lactam group of antibiotic (penicillin) they affect cell wall of bacteria. How- cell wall of most bacteria contains a rigid girdle of peptidoglycan, which protect the cell from rupture from hypotonic environment. Active cells must constantly synthesize new peptidoglycan and transport it to its proper in the cell envelope so the penicillin and cephalosporins react with one or more of the enzyme required to complete this process, causing cell to develop weak point at growth sites and to becomes osmotically fragile hence lysis . Note; antibiotics are active only in young and growing cell because old, inactive, or dormant cell do not synthesize peptidoglycan. Action; penicillin and cephalosporins bind and block peptidase that cross links the glycan molecule , there by interrupting the completion of the cell wall. How resistance occur-The bacteria produce beta lactamase or penicilliase enzyme that that bind with beta lactam(active site ) of the penicillin and destroy it hence cillin will no longer active again. 2.Cell membranes The antibiotics that damage cell membrane they have specificity for microbial groups based on differences of their cell membranes. Action-the antibiotics polymyxins from bacillus polymyxa it is usually interact with membrane phospholipids and cause leakage of proteins and nitrogen bases. How resistance occur- the receptor that transport the drug toward the cell is altered, hence new receptor is formed hence the antibiotic will fail to bind with the receptor sites of the cell membrane. 3.NUCLEIC ACIDS The antibiotics like fluoroquinolones that are chemically related to quinine , they are mostly affect the bacteria DNA, Action- the antibiotics fluoroquinolones they affect bacteria by binding to DNA gyrase and related enzyme topoisomerase iv hence the DNA replication of the bacteria will fail, but the antibiotic rifampin which is essential for tuberculosis for this his primary action is blocking action of RNA polymerase hence preventing transcription, How resistance occur- The microbes they activate the specialized membrane of proteins and continually pump the drug out of the cell. 4.INHIBITION OF PROTEIN SYNTHESIS. In bacteria cell there is specialized organelles that is responsible in protein synthesis and these are ribosome. Action of antibiotics to microbes ribosome -The antibiotics like aminoglyicoside sthat have one or more amino sugars and an aminocyclitol they affect the synthesis of protein synthesis in ribosome by binding to one of ribosomal sub units hence the protein synthesis will be failed. How resistance occur-the bacteria of microbes can become resistant to amino glycosides when point in ribosomal proteins arise and not only that the microbes is associated with the alteration or 50s ribosomal binding site. 5.BLOCKS ON KEY METABOLLIC PATTERNS The drug like sulfonamides or sulfa drugs they do function as metabolic analog to block synthesis of folic acid by bacteria. Action of antibiotics-the sulfa drug they do function as metabolic analog since they block the synthesis of folic acid by bacteria hence no metabolic will run anymore. How resistance occur-the action antimetabolities can be circumvented if a microbe develop and alternative metabolic pathway or enzyme . Sulfonamides and trimethoprim resistance develops when microbes deviate from the usual patterns of folic acid but fung can acquire resistance to flucytosine by completely shutting off certain metabolic activities. QN,C. HOW TO PREVENT ANTIBIOTICS RESISTANCE SPREAD IN MICROBES. There are ways that if they could be used properly the spread of antibiotics resistance in microbes will be prevented and these are. General principle for use of antibiotics 1.Physicians have the responsibility for making an accurate diagnosis and prescribing the correct drug therapy. Hence he/she could make the correct diagnosis , find the site of infection and organisms responsible than use antibioagent after finding the sensitivity. 2.Remove barrier e.g. Lack of free drainage of abscesses(so drain the abscess before starting antibiotics) 4.Select the best drug i.e. Activity of the drug should match with the infecting organism .The drug should be capable of reaching the site of infection. 5.Patients must comply with and careful follow the physicians guidelines. It is important for the patient to take the correct dosage , by the best route , for appropriate period. This diminishes the selection for mutants that can resists low drug levels, and ensure elimination of the pathogens. 6.Therapy should continued till apparent cure is achieved and three days more to avoid relapse. 7.In typhoid , tuberculosis and endocardits the drug should be continued for a longer time after apparent clinical cure. 8.Combined therapy is administration of two or more drugs together and increase that at least one of the drugs will be effective and that a resistant strain of either drug will not be able to persist. The success depends on carefully choosing drugs that have different metabolic targets .it is unlikely a microbe would posses resistance to multiple drugs with distinct target. 9.Microbiological examination to be done ;to prove the complete cure after withdrawal of antibiotics agent this helps to prevent the rise of antibiotics resistance in case where the microbes wont be diminishes. 10. Prophylactic chemo therapy for surgical and dental procedure should start at the time of surgery and continue for 48 hours to reduce the risk of development of antibiotics resistance. hydrogen peroxide, mouthwash. The antiseptic they mostly used in a body skin living tissue which they do help to remove microbes from the body skin. .................... CHAGUO NI LAKO........................