ANTIBIOTIC ANTIBIOTIC RESISTANCERESISTANCEANTIBIOTIC ANTIBIOTIC RESISTANCERESISTANCE

Submitted By;Submitted By;May J. HamoudaMay J. HamoudaSupervised By;Supervised By;

Dr. Abdelraouf AElmanamaDr. Abdelraouf AElmanama..

20052005

Submitted By;Submitted By;May J. HamoudaMay J. HamoudaSupervised By;Supervised By;

Dr. Abdelraouf AElmanamaDr. Abdelraouf AElmanama..

20052005

❊ ❊ INTRODUCTION ❊INTRODUCTION ❊

Penicillin (Second World War ).Penicillin (Second World War ). Scottish physician Alexander Scottish physician Alexander

Fleming in 1928 .Fleming in 1928 . Staphylococcus aureus.Staphylococcus aureus. Antibiotic resistance spreads fast. Antibiotic resistance spreads fast.

Between 1979 and 1987.Between 1979 and 1987.

❊ ❊ DIFINITIOM ❊DIFINITIOM ❊

Antibiotics, also known as Antibiotics, also known as antimicrobial drugs, are drugs that antimicrobial drugs, are drugs that fight infections caused by bacteria. fight infections caused by bacteria.

❊ ❊ Microbial Sources of Antibiotics ❊Microbial Sources of Antibiotics ❊

Bacteria:Bacteria: Streptomyces: Streptomyces: Amphotericin B, Amphotericin B,

Chloramphenicol, Erythromycin, Neomycin, Chloramphenicol, Erythromycin, Neomycin, Rifampin, Streptomycin,Tetracycline Rifampin, Streptomycin,Tetracycline Vancomycin.Vancomycin.

Micromonospora: Micromonospora: Gentamicin.Gentamicin. Bacillus: Bacillus: Bacitracin, Polymyxin.Bacitracin, Polymyxin.

Fungi:Fungi: Penicillium: Penicillium: Griseofulvin, Penicillin.Griseofulvin, Penicillin. Cephalosporium: Cephalosporium: CephalosporinsCephalosporins..

❊❊MECHANISMS OF ANTIBIOTIC ACTION❊MECHANISMS OF ANTIBIOTIC ACTION❊

The basic mechanisms against bacteria are the following:The basic mechanisms against bacteria are the following:

· Disruption of the cell wall.· Disruption of the cell wall.

· Inhibition of protein synthesis.· Inhibition of protein synthesis.

· Inhibition of nucleic acid synthesis.· Inhibition of nucleic acid synthesis.

· Antimetabolite activity.· Antimetabolite activity.

❊ ❊ Mechanisms of resistance to Mechanisms of resistance to antimicrobials ❊antimicrobials ❊

What are the reasons for this resistance?What are the reasons for this resistance?

Let's see how a Let's see how a beta lactambeta lactam such as penicillin disturbs this such as penicillin disturbs this

processprocess

❊ ❊ The main methods of resistance The main methods of resistance ❊❊

1.1. Diminished Diminished transport into the transport into the bacterium.bacterium.

The bacterium on the The bacterium on the left has lost the porin left has lost the porin that normally that normally transports the transports the antibiotic into the antibiotic into the cell.cell.

OR it has a pump that OR it has a pump that pumps out the beta pumps out the beta lactam as fast as it lactam as fast as it comes incomes in..

CONTINUE….CONTINUE….

2. An altered binding site.2. An altered binding site.

This bacterium has a slightly altered PBP. This bacterium has a slightly altered PBP. The PBP can still carry out its function, but The PBP can still carry out its function, but is no longer inhibited by the penicillin, is no longer inhibited by the penicillin, which cannot bind to it. which cannot bind to it.

CONTINUE….CONTINUE…. 3. Enzymes that break down the antibiotic.3. Enzymes that break down the antibiotic.

This is an important method of resistance for many This is an important method of resistance for many bacteria. Beta lactams are for example broken down by bacteria. Beta lactams are for example broken down by beta lactamasesbeta lactamases. There is a whole host of beta . There is a whole host of beta lactamases. lactamases.

44. Another method of resistance - an . Another method of resistance - an alternative pathway!alternative pathway!

The agent is The agent is trimethoprimtrimethoprim. Bacteria need to make their . Bacteria need to make their own folic acid, and they normally do this using a vital own folic acid, and they normally do this using a vital pathway that involves the enzyme dihydrofolate pathway that involves the enzyme dihydrofolate reductase. Trimethoprim inhibits this bacterial enzyme, reductase. Trimethoprim inhibits this bacterial enzyme, preventing folate synthesis and thus interfering with the preventing folate synthesis and thus interfering with the ability to make DNA. But some wily bacteria bypass this ability to make DNA. But some wily bacteria bypass this step by acquiring a new enzyme that bypasses the old, step by acquiring a new enzyme that bypasses the old, inhibited dihydrofolate reductase. The new enzyme inhibited dihydrofolate reductase. The new enzyme comes from plasmids. comes from plasmids.

❊ ❊ How Antibiotic Resistance How Antibiotic Resistance Happens ❊Happens ❊

❊ ❊ Mechanisms of Evolution ❊Mechanisms of Evolution ❊

❊ ❊ Conjugation.Conjugation.

❊❊TransductionTransduction..

❊❊Transformation.Transformation.

❊ ❊ Genetic mechanisms ❊Genetic mechanisms ❊

The basic mechanisms of The basic mechanisms of transformation, transduction, and transformation, transduction, and conjugation provide a starting point conjugation provide a starting point for more complex mechanisms of for more complex mechanisms of the development and spread of the development and spread of antibiotic resistance. antibiotic resistance.

1.1. Point mutations.Point mutations.Spontaneous changes in single nucleotides Spontaneous changes in single nucleotides have produced resistance to some antibiotics. have produced resistance to some antibiotics. Point mutations are usually random, and thus Point mutations are usually random, and thus occur before exposure to antibiotics.occur before exposure to antibiotics.

CONTINUE….CONTINUE….2. Intragenic recombination.2. Intragenic recombination.When smaller fragments of DNA are incorporated When smaller fragments of DNA are incorporated

through transformation, intragenic recombination through transformation, intragenic recombination and mosaic genes result. Mosaic genes contain DNA and mosaic genes result. Mosaic genes contain DNA of the original allele in some locations, but from of the original allele in some locations, but from different genes or organisms in other locations. This different genes or organisms in other locations. This is a result of intragenic recombination.is a result of intragenic recombination.

3.Transposons.3.Transposons. Transposable elements are small regions of DNA that Transposable elements are small regions of DNA that

can move from one place to another in the genome. can move from one place to another in the genome. Therefore, these play a role in evolution of Therefore, these play a role in evolution of antibiotic resistance. antibiotic resistance. Genes in transposons can Genes in transposons can be transferred between bacterial hosts by be transferred between bacterial hosts by transposition into bacterial plasmids, which transposition into bacterial plasmids, which can then undergo conjugation. Transposons can then undergo conjugation. Transposons make multiple antibiotic resistances. make multiple antibiotic resistances.

CONTINUE….CONTINUE….

❊ ❊ Mechanisms of Resistance Mechanisms of Resistance ❊❊

The various types of antibiotics target different aspects The various types of antibiotics target different aspects of the bacterial life-cycle. An antibiotic has to interact of the bacterial life-cycle. An antibiotic has to interact with some molecule in the cell so that an essential with some molecule in the cell so that an essential component does not function or is not made properly in component does not function or is not made properly in order to kill the bacteria. The interaction would imply order to kill the bacteria. The interaction would imply that the antibiotic's structure and composition allows it that the antibiotic's structure and composition allows it to interact with that molecule. There are many to interact with that molecule. There are many mechanisms by which this can occur. The antibiotic mechanisms by which this can occur. The antibiotic could interact with an enzyme because it is similar to could interact with an enzyme because it is similar to the substrate and thus block enzyme function. the substrate and thus block enzyme function.

There are three main mechanisms by which bacteria There are three main mechanisms by which bacteria can avoid these interactions. can avoid these interactions.

CONTINUE….CONTINUE….1.1. Alteration of antibiotic.Alteration of antibiotic.

        The structure of the antibiotic is essential to its The structure of the antibiotic is essential to its interaction with its target molecule. Any alterations, such interaction with its target molecule. Any alterations, such as the hydrolysis of the antibiotic into several pieces or the as the hydrolysis of the antibiotic into several pieces or the mere cleavage of a single bond, would change the mere cleavage of a single bond, would change the antibiotic's ability to affect bacteria.antibiotic's ability to affect bacteria.

2.2. Target-mediated resistanceTarget-mediated resistance.. The structure of the antibiotic and of its target The structure of the antibiotic and of its target

molecule is important to their interaction. The production molecule is important to their interaction. The production of a target molecule which has a lower affinity for the of a target molecule which has a lower affinity for the antibiotic, or any other alteration of the target molecule antibiotic, or any other alteration of the target molecule will affect the potency of the antibiotic on the bacterium. will affect the potency of the antibiotic on the bacterium.

3.3. Exclusion of antibiotic.Exclusion of antibiotic. The antibiotic is prevented from entering the cell. The antibiotic is prevented from entering the cell.

This may be by a change in cell membrane composition, or This may be by a change in cell membrane composition, or specific membrane structures may prevent the antibiotic specific membrane structures may prevent the antibiotic from entering. Many bacteria naturally have a means to from entering. Many bacteria naturally have a means to exclude small molecules. exclude small molecules.

❊❊Agricultural Use of Antibiotics ❊Agricultural Use of Antibiotics ❊ Antibiotics are used in both food-producing animals and on Antibiotics are used in both food-producing animals and on

food plants to treat specific diseases afflicting specific animals food plants to treat specific diseases afflicting specific animals and plants and to prevent the spread of diseases that are may and plants and to prevent the spread of diseases that are may have occurred in particular herds, flocks and crops under have occurred in particular herds, flocks and crops under certain conditions. certain conditions.

Antibiotics are also used in food animals to enhance their Antibiotics are also used in food animals to enhance their growth rate and feed efficiency.growth rate and feed efficiency.

Since the 1940s, farmers have used antibiotics as a production Since the 1940s, farmers have used antibiotics as a production tool in raising livestock. They add antibiotics to feed to tool in raising livestock. They add antibiotics to feed to counteract the effects of crowded living conditions and poor counteract the effects of crowded living conditions and poor hygiene, which lessen the animal's ability to reach market hygiene, which lessen the animal's ability to reach market weight on time. weight on time.

It is estimated that more than 40 percent of the antibiotics It is estimated that more than 40 percent of the antibiotics manufactured in the U.S. are given to animals. Some of that manufactured in the U.S. are given to animals. Some of that amount goes to treating or preventing infection, but most is amount goes to treating or preventing infection, but most is mixed into feed to promote growth.mixed into feed to promote growth.

24,500,000 pounds of antibiotics are used in animal feed during 24,500,000 pounds of antibiotics are used in animal feed during the 1990's. The antibiotics are added to promote animal the 1990's. The antibiotics are added to promote animal growth, and many of the antibiotics the animalsare given are growth, and many of the antibiotics the animalsare given are the exact same as those that are used to treat human diseases.the exact same as those that are used to treat human diseases.

❊❊Multiple-drug resistance ❊Multiple-drug resistance ❊ Multiple-drug resistance occurs Multiple-drug resistance occurs

when bacteria are resistant to more when bacteria are resistant to more than one antibiotic. This is generally than one antibiotic. This is generally the rule rather than the exception the rule rather than the exception among resistant bacteria. This among resistant bacteria. This situation has largely occurred situation has largely occurred through the sequential use of through the sequential use of multiple different antibiotics. The multiple different antibiotics. The first antibiotic began by selecting a first antibiotic began by selecting a single resistance gene. Eventually, single resistance gene. Eventually, however, bacteria resistant to the however, bacteria resistant to the first antibiotic picked up resistance first antibiotic picked up resistance to others as they were introduced to others as they were introduced into the environment. into the environment.

❊ ❊ Factors that contribute to Factors that contribute to

antibiotic resistance ❊antibiotic resistance ❊ Misuse and overuse of antibiotics in Misuse and overuse of antibiotics in

humans, animals and agriculture humans, animals and agriculture Demand for antibiotics when Demand for antibiotics when

antibiotics are not appropriate antibiotics are not appropriate Failure to finish an antibiotic Failure to finish an antibiotic

prescription prescription Availability of antibiotics without a Availability of antibiotics without a

prescription in some countriesprescription in some countries

How can you prevent How can you prevent antibiotic-resistant infections? antibiotic-resistant infections? ❊❊

Talk with your health care provider about Talk with your health care provider about antibiotic resistance. antibiotic resistance. Ask whether an antibiotic is likely to be Ask whether an antibiotic is likely to be

beneficial for your illness. beneficial for your illness. Ask what else you can do to feel better Ask what else you can do to feel better

sooner. sooner. Do not take an antibiotic for a viral infection Do not take an antibiotic for a viral infection

like a cold or the flu.like a cold or the flu. Do not save some of your antibiotic for the Do not save some of your antibiotic for the

next time you get sick.next time you get sick. Take an antibiotic exactly as the doctor tells Take an antibiotic exactly as the doctor tells

you.you. Do not take an antibiotic that is prescribed for Do not take an antibiotic that is prescribed for

someone else. someone else.

THE ENDTHE END