Control of Bacteria and Pathogens Chapter 9 –Chemical and physical agents

1. Control of Bacteria and Pathogens Chapter 9 –Chemical and physical agents (also see Chapter 25 about food preservation ) Chapters 10 – Chemotherapeutic agents Who and Why? 1) Food industry 2) Public welfare 3) Manufacturing Industry 4) Individual/ population Combating spread through 1) antimicrobial agents 2) aseptic techniques 3) epidemiological strategies Control of Bacteria and Pathogens

2. How are Physical and Chemical agents antimicrobial? -- damage to membranes -- denaturation of proteins -- DNA damage How do different agents control growth “- cidals” (e.g., heating) vs “- statics” (e.g., chilling) Control of Bacteria and Pathogens

3. Physical & Chemical Agents – in Chapter 9 Read about physical gents -- Heat-related methods -- Filtration -- osmotic pressure -- Ionizing and nonionizing radiation Chemical agents can be Antisepticsor disenfectantsor chemotherapeutics -- how are these different? Read about non-chemotherapeutic chemical agents -- alcohols -- acidification -- sulfactants -- heavy metals -- gaseous agents Some of these agents are important for Food preservation Control of Bacteria and Pathogens

4. “Noah carried the slabs of meat into the kitchen and cut it into small salting blocks, and Ma patted the coarse salt in, laid it piece by piece in the kegs, careful that no two pieces touched each other. She laid the slabs like bricks, and pounded salt in the spaces.” John Steinbeck, The Grapes of Wrath Food preservation see Chapter 25 What does “spoilage” mean” ‘Shelf life’ prevent microbial growth maintain food quality ‘commercial sterilization’ Methods 1) Food modifications drying acidification salting 2) Temperature heating Pasteurization cooling Control of Bacteria and Pathogens

5. Food preservation, con’t. 3) Reduce O2content canning, jarring, etc 4) Chemical preservatives Benzoates, sorbates, sulfites, nitrites [BHT and BHA are antioxidants] Concerns FDA and the GRAS list Na Nitrite & ‘nitrosamines’ 5) Ionizing radiation cobalt-60 Food approved by FDA for irradiation spices & grains (to kill insects) imported fruits (to control insects) potatoes & onions (to inhibit sprouting) poultry and red meats (to control pathogens) Other countries irradiate much more food Control of Bacteria and Pathogens

6. Chemotherapeutic agents (Chapter 11) Some Ideal attributes: 1) selective toxicity 2) stability … in body ‘biotransformation’ … on shelf … with other substances 3) limited solubility Two categories 1) Synthetic drugs 2) Antibiotics “Chemicals produced by one organism that are effective at low concentration in inhibiting growth of another organism.” semi-synthetic Abs Acyclovir: a synthetic antiviral agent Control of Bacteria and Pathogens

7. Synthetic drugs Discovery Paul Ehrlich’s ‘Magic Bullet’ Syphilis Salvarsan-606: 1909 1930s: Age of the Sulfa-Drugs Sulfanilamide an “antimetabolite” or “metabolite analog” only ‘bacteriostatic’ Control of Bacteria and Pathogens

8. Antibiotics Discovery Alexander Fleming Penicillium notatum ‘bacteriocidal’ Development WWII Oxford University Howard Florey and Norman Heatley U.S. mass production Major sources of antibiotics Bacteria (Streptomyces, Bacillus) Fungi (Penicillium, Cephalosporium) Control of Bacteria and Pathogens

9. Fluoroquinolone Tetracyclin Erythomycin Polymyxin-B Rifamycin Streptomycin Major families of Antibiotics β-Lactam -- penicillin, cephalosporins, etc Aminoglycosides -- steptomycin, neomycin, etc Tetracyclines Quinolones Macrolides – e.g., erythomycin Polymyxins – polymycin-B Rifamycins – e.g., rifampin Control of Bacteria and Pathogens

10. Properties of Antibiotics Spectrum of activity narrow broad Mechanisms of action -- of antibiotics (Anti-virals in Virology ppt) Neomycin Bacitracin Polymixin Control of Bacteria and Pathogens

11. Dr Spilatro’s Big Adventure The antibiotics 1. Ciprofloxacin - Fluoroqinolone 2. Levafloxin - Fluoroqinolone 3. Ceftriaxone - β-lactam (cephalosporin derivative) 4. Tobramycin - Aminoglycoside (from Streptomyces) 5. Piperamycin - β-lactam (“Zocyn”) (penicillin derivative) + Tazobactam - β-lactamase inhibitor 6. Doripenem – carbepenem (modified β-lactam) The bacterium ESBL E. coli Extended Spectrum β-lactamase -- carried on plasmid Multiple Ab resistance Control of Bacteria and Pathogens

12. Properties of Antibiotics, con’t. Examples of Adverse reactions 1) Toxicity: “therapeutic dose” vs “toxic dose” levels Tissue damage (e.g., kidney) bacitracin, polymyxin, amyloglycosides -- Tobramycin Congenital defects tetracycline Digestive disorders many 2) Allergic reactions penicillin & cephalosporins 3) Kill indigenous bacteria -- growth of Clostridium difficile Control of Bacteria and Pathogens

13. Resistance to Antibiotics IntrisicvsAcquired resistance Mechanisms 1) Enzymatic inactivation β-lactamase 2) Alteration of site of action streptomycin, erythromycin 3) change in cell membrane or cell wall permeability 4) membrane pumps (efflux) somewhat indescriminate Control of Bacteria and Pathogens

14. Resistance to Antibiotics Epidemiological aspects Current serious problems MRSA VRE CRE My ESBL E. coli Resistant Ampicillin – β-lactam Aztreonam – monobactam Cefazolin – β-lactam Cefuroxime – β-lactam Ceftriaxone – β-lactam Ceftazidme – β-lactam Ciprofloxacim – fluoroqinolone Levaquin – fluoroqinolone Gentamicin – aminoglycoside Tmp/Smx – sulfonamides Ab resistance in 75 VRE isolates Moritz & Hergenrother 2007 PNAS 104:311-316 Sensitive (I) Ticarcillin (β-lactam) + clavulanate (inhibitor) Tobramycin – aminoglycoside Amikacin – aminoglycoside Pip/Tazo – β-lactam + inhibitor Imipenem – monobactam Control of Bacteria and Pathogens

15. Resistance to Antibiotics Epidemiological aspects Controlling spread 1) complete prescription 2) optimize dosage ` 3) double prescribe 4) avoid indescriminate use 5) reduce agricultural uses fluoroquinolones and Campylobacter jejuni Control of Bacteria and Pathogens