ANTIBIOTIC RESISTANCE

1. ANTIBIOTIC RESISTANCE Submitted By;May J. HamoudaSupervised By;Dr. Abdelraouf AElmanama.2005

2. ❊ INTRODUCTION ❊ • Penicillin (Second World War ). • Scottish physician Alexander Fleming in 1928 . • Staphylococcus aureus. • Antibiotic resistance spreads fast. Between 1979 and 1987.

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

4. ❊ Microbial Sources of Antibiotics ❊ • Bacteria: • Streptomyces: Amphotericin B, Chloramphenicol, Erythromycin, Neomycin, Rifampin, Streptomycin,Tetracycline Vancomycin. • Micromonospora: Gentamicin. • Bacillus: Bacitracin, Polymyxin. • Fungi: • Penicillium: Griseofulvin, Penicillin. • Cephalosporium: Cephalosporins.

5. ❊MECHANISMS OF ANTIBIOTIC ACTION❊ • The basic mechanisms against bacteria are the following: · Disruption of the cell wall. · Inhibition of protein synthesis. · Inhibition of nucleic acid synthesis. · Antimetabolite activity.

6. ❊ Mechanisms of resistance to antimicrobials ❊ What are the reasons for this resistance?

7. Let's see how a beta lactam such as penicillin disturbs this process

8. ❊ The main methods of resistance ❊ • Diminished transport into the bacterium. • The bacterium on the left has lost the porin that normally transports the antibiotic into the cell. • OR it has a pump that pumps out the beta lactam as fast as it comes in.

9. CONTINUE…. 2. An altered binding site. • This bacterium has a slightly altered PBP. The PBP can still carry out its function, but is no longer inhibited by the penicillin, which cannot bind to it.

10. CONTINUE….3. Enzymes that break down the antibiotic. • This is an important method of resistance for many bacteria. Beta lactams are for example broken down by beta lactamases. There is a whole host of beta lactamases. 4. Another method of resistance - an alternative pathway! • The agent is trimethoprim. Bacteria need to make their own folic acid, and they normally do this using a vital pathway that involves the enzyme dihydrofolate reductase. Trimethoprim inhibits this bacterial enzyme, preventing folate synthesis and thus interfering with the ability to make DNA. But some wily bacteria bypass this step by acquiring a new enzyme that bypasses the old, inhibited dihydrofolate reductase. The new enzyme comes from plasmids.

11. ❊ How Antibiotic Resistance Happens ❊ • ❊ Mechanisms of Evolution ❊

12. ❊ Conjugation. ❊Transduction. ❊Transformation.

13. ❊ Genetic mechanisms ❊ The basic mechanisms of transformation, transduction, and conjugation provide a starting point for more complex mechanisms of the development and spread of antibiotic resistance. • Point mutations.Spontaneous changes in single nucleotides have produced resistance to some antibiotics. Point mutations are usually random, and thus occur before exposure to antibiotics.

14. CONTINUE…. 2. Intragenic recombination. When smaller fragments of DNA are incorporated through transformation, intragenic recombination and mosaic genes result. Mosaic genes contain DNA of the original allele in some locations, but from different genes or organisms in other locations. This is a result of intragenic recombination. 3.Transposons. Transposable elements are small regions of DNA that can move from one place to another in the genome. Therefore, these play a role in evolution of antibiotic resistance. Genes in transposons can be transferred between bacterial hosts by transposition into bacterial plasmids, which can then undergo conjugation. Transposons make multiple antibiotic resistances.

15. CONTINUE….

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

17. CONTINUE…. • Alteration of antibiotic.The structure of the antibiotic is essential to its interaction with its target molecule. Any alterations, such as the hydrolysis of the antibiotic into several pieces or the mere cleavage of a single bond, would change the antibiotic's ability to affect bacteria. • Target-mediated resistance.The structure of the antibiotic and of its target molecule is important to their interaction. The production of a target molecule which has a lower affinity for the antibiotic, or any other alteration of the target molecule will affect the potency of the antibiotic on the bacterium. • Exclusion of antibiotic. The antibiotic is prevented from entering the cell. This may be by a change in cell membrane composition, or specific membrane structures may prevent the antibiotic from entering. Many bacteria naturally have a means to exclude small molecules.

18. ❊Agricultural Use of Antibiotics ❊ • Antibiotics are used in both food-producing animals and on food plants to treat specific diseases afflicting specific animals and plants and to prevent the spread of diseases that are may have occurred in particular herds, flocks and crops under certain conditions. • Antibiotics are also used in food animals to enhance their growth rate and feed efficiency. • Since the 1940s, farmers have used antibiotics as a production tool in raising livestock. They add antibiotics to feed to counteract the effects of crowded living conditions and poor hygiene, which lessen the animal's ability to reach market weight on time. • It is estimated that more than 40 percent of the antibiotics manufactured in the U.S. are given to animals. Some of that amount goes to treating or preventing infection, but most is mixed into feed to promote growth. • 24,500,000 pounds of antibiotics are used in animal feed during the 1990's. The antibiotics are added to promote animal growth, and many of the antibiotics the animalsare given are the exact same as those that are used to treat human diseases.

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

20. ❊ Factors that contribute to antibiotic resistance ❊ • Misuse and overuse of antibiotics in humans, animals and agriculture • Demand for antibiotics when antibiotics are not appropriate • Failure to finish an antibiotic prescription • Availability of antibiotics without a prescription in some countries

21. How can you prevent antibiotic-resistant infections? ❊ • Talk with your health care provider about antibiotic resistance. • Ask whether an antibiotic is likely to be beneficial for your illness. • Ask what else you can do to feel better sooner. • Do not take an antibiotic for a viral infection like a cold or the flu. • Do not save some of your antibiotic for the next time you get sick. • Take an antibiotic exactly as the doctor tells you. • Do not take an antibiotic that is prescribed for someone else.

22. THE END