Control of Bacteria and Pathogens 1

Control of Bacteria and PathogensChapter 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 through1) antimicrobial agents

2) aseptic techniques

3) epidemiological strategies

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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)

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Physical & Chemical Agents – in Chapter 9

Read about physical gents-- Heat-related methods -- Filtration-- osmotic pressure-- Ionizing and nonionizing radiation

Chemical agents can be

Antiseptics or disenfectants or 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

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Food preservationsee Chapter 25

What does “spoilage” mean”

‘Shelf life’ prevent microbial growthmaintain food quality ‘commercial sterilization’

Methods

1) Food modificationsdrying

acidification

salting

2) Temperatureheating

Pasteurization

cooling

“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

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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 radiationcobalt-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

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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

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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’

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Antibiotics

Discovery

Alexander Fleming

Penicillium notatum

‘bacteriocidal’

Development WWII

Oxford UniversityHoward Florey andNorman Heatley

U.S. mass production

Major sources of antibioticsBacteria (Streptomyces, Bacillus)Fungi (Penicillium, Cephalosporium)

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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

Streptomycin

Tetracyclin

FluoroquinoloneErythomycin

Polymyxin-B

Rifamycin

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Properties of Antibiotics

Spectrum of activity

narrow

broad

Mechanisms of action -- of antibiotics

(Anti-virals in Virology ppt)

NeomycinBacitracinPolymixin

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Dr Spilatro’s Big Adventure

The antibiotics1. Ciprofloxacin - Fluoroqinolone2. 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

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Properties of Antibiotics, con’t.

Examples of Adverse reactions1) Toxicity: “therapeutic dose” vs “toxic dose” levels

Tissue damage (e.g., kidney)bacitracin, polymyxin, amyloglycosides

-- TobramycinCongenital defects

tetracyclineDigestive disorders

many2) Allergic reactions

penicillin & cephalosporins3) Kill indigenous bacteria

-- growth of Clostridium difficile

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Resistance to Antibiotics

Intrisic vs Acquired resistance

Mechanisms

1) Enzymatic inactivationβ-lactamase

2) Alteration of site of actionstreptomycin, erythromycin

3) change in cell membrane orcell wall permeability

4) membrane pumps (efflux)somewhat indescriminate

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Resistance to AntibioticsEpidemiological aspects

Current serious problems

MRSA

VRE

CRE

My ESBL E. coli

ResistantAmpicillin – β-lactamAztreonam – monobactamCefazolin – β-lactamCefuroxime – β-lactamCeftriaxone – β-lactamCeftazidme – β-lactamCiprofloxacim – fluoroqinoloneLevaquin – fluoroqinoloneGentamicin – aminoglycosideTmp/Smx – sulfonamides

Ab resistance in 75 VRE isolatesMoritz & Hergenrother 2007 PNAS 104:311-316

Sensitive (I) Ticarcillin (β-lactam) + clavulanate (inhibitor)Tobramycin – aminoglycosideAmikacin – aminoglycosidePip/Tazo – β-lactam + inhibitorImipenem – monobactam

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Resistance to AntibioticsEpidemiological aspects

Controlling spread1) complete prescription

2) optimize dosage

` 3) double prescribe

4) avoid indescriminate use

5) reduce agricultural usesfluoroquinolones andCampylobacter jejuni