MICROBIOLOGY – ALCAMO

LECTURE: Chemotherapeutic Agents

and Antibiotics

Chemotherapeutic Agents and Antibiotics

• For centuries, doctors thought that drastic measures were necessary to save a patient from infectious disease:– ____________ and ____________– Large doses of chemicals– Ice water baths– ____________– These treatments probably made a bad situation

worse

Chemotherapeutic Agents and Antibiotics

• In 1825, doctors in Boston and London wanted to see what would happen if these treatments were not given

• They found that no treatment at all was better• For the next 60 years it became the doctor’s

job to ________________________, explain it to the family, and sit by caring for the patient

Chemotherapeutic Agents and Antibiotics

• Late 1800’s – ____________• ________________________• Doctors understood where disease comes from but could do little• Tuberculosis killed 1 of every 7 people that died• Streptococcal heart valve disease, pneumonia,

and meningitis ____________

Chemotherapeutic Agents and Antibiotics

• 1940’s – chemotherapeutic agents and ____________ were discovered

• Doctor’s learned that they could kill ____________ in the body without harming the body itself

• Doctors were altering the course of ____________ which made a dramatic change in the world

Chemotherapeutic Agents & Antibiotics

• Must be more ____________ to MO than host cells

• ____________ only helps the immune system to control the infection

• The immune system ultimately stops MOs

Chemotherapeutic Agents

• Produced in lab, inorganic chemicals• Sulfur, Arsenic, Quinine, Nicotinic Acid• Still major medical applications• Can be quite ____________ to patient

Antibiotics

• Originally: Chemical produced by an MO which ____________ ____________of other MOs

• Now synthesized in labs, Organic Chem

Chemotherapeutic Agents & Antibiotics

• Have ____________ ____________ mechanisms

• Select for specific MO according to which life process you need to disrupt:– ____________ ____________ – Cell Wall structure– ___________ ____________ ____________ – RNA or DNA synthesis– Chemical ____________

History of Chemotherapy

• Paul ____________ – worked with stains and dyes and found out they had antimicrobial properties

• Collaborated with Sahachiro Hata to produce Salvarsan – 1st chemotherapeutic

drug (___________ )• Problems:

– Local reaction at injection site– Church wanted ____________ to be a deterrent to

immoral behavior

History of Chemotherapy• For the next 20 years, German scientists kept

testing dyes for ____________ ____________ • Gerhard Domagk tested prontosil dye on his

own daughter when she became ill with ____________ and she recovered

Sulfa Drugs

• It was determined that the active ingredient in prontosil is ____________ • In 1940, D.D. Woods and E.M. Fildes proposed a

mechanism of action for ____________ ____________

• It showed how they could interfere with ____________ ____________ without damaging host tissues

Competitive Inhibition

• Bacteria need folic acid to produce nucleic acids (____________________ )

• Bacteria have an ____________ to make folic acid – they can’t get folic acid from ____________ like we do

• This ____________ joins PABA with 2 other components to make folic acid

• Sulfanilimide looks like PABA and ____________ will bind to it instead of PABA

Sulfa Drugs

• ____________ :– Sulfamethoxazole – Used for urinary tract infections and pneumonia

• ____________ :– Sulfisoxazole– Used for vaginal infections, conjunctivitis and

toxoplasmosis

Antibiotics• Word means “___________ _________ ”• Chemical products or derivatives of certain

organisms that are ____________ to other organisms

• How did organisms gain the ability to produce __________?

– Random genetic mutation– Evolutionary advantage

Antibiotics

• Mainstay for help with ____________ ____________ . Used for some fungal and protozoal infectionsUseless on ____________ (2ndary Bact Inf)

• Usually ____________ / ____________, some patients dangerously hypersensitive

Alexander Fleming• Discovered ____________ • One of his agar plates containing staphylococci became contaminated with a green mold• He noticed the staphylococci didn’t __________

____________ ___________• He identified the mold as a species of

____________ and he named its substance penicillin

Zone of Inhibition

Penicillin• Isolated from a fungus - ____________

• First antibiotic, 1940’s• Interferes with cell wall

synthesis• Effective against G+ MOs

Few G- with massive doses

• “____________ : a very large family of drugs

This bacterium is lysing because an antibiotic disrupted its cell wall. Why doesn’t the antibiotic lyse human cells?

Disadvantages of Penicillin

• 1. ____________ or allergy– Swelling of the eyes or wrists– Flushed or itchy skin, hives– Shortness of breath

• 2. ____________ ____________ bacteria– Produce ____________ , an enzyme that converts

penicillin into a useless compound– Use too many ____________ – natural selection

of antibiotic resistant bacteria

Semi-synthetic Penicillins

• In the 1950’s the beta-lactam nucleus of the ____________ molecule was identified and synthesized

• New ____________ were created by attaching different groups to this nucleus:

____________ ____________

Cephalosporin

• Isolated from a ____________ - Cephalosporium• Interferes with ____________ ___________• Similar to ____________ – can be used in allergic

persons and with resistant MOs• Interferes with some

G+ and some G- MOs

Streptomycin• Isolated from a filamentous (mold-like) soil

bacteria - ____________ ____________ • Attaches to ____________ , blocks messenger

RNA• Carefully used, toxic side effects (____________ )• “____________ ” a very large

family of drugs– Neosporin contains Neomycin

Chloramphenicol

• Streptomyces’ 2nd family of drugs:Original Prod: Chloromycetin

• 1st “____________ ____________ ” AntibioticWide variety of G+ and G- MOs

• Interferes with protein

synthesis, ____________

blocked from mRNA

Tetracycline

• ____________ ____________ antibiotics• Can be taken orally and were used widely in the

1950’s and 1960’s• Overused, so __________ ________was

eliminated from the intestines• Then ____________ (Candida albicans) flourished

and antifungal antibiotics had to be taken• Also caused gray-brown tooth ____________

Antimicrobial Drugs• ____________ : The use of drugs to treat a

disease• ____________ ____________ : Interfere with

the growth of microbes within a host• ____________ : A substance produced by a

microbe that, in small amounts, inhibits another microbe

• ____________ ____________ : A drug that kills harmful microbes without damaging the host

The Action of Antimicrobial Drugs

• ____________ – Kill microbes directly

• ____________ – Prevent microbes from growing

Antibiotic Assays• 1. ____________ ____________ ____________ –

determines the smallest amount of antibiotic necessary to inhibit a test organism– Prepare a set of tubes with different ____________ of an

antibiotic– The tubes are ____________ with the test organism,

incubated and examined for growth– Extent of ____________ gets lower with increasing

concentration of antibiotic– When growth ____________ to occur – you have reached

the minimum inhibitory concentration (MIC)

Antibiotic Assays

• 2. Agar or disk ____________ ____________ – operates on the principle that antibiotics will diffuse from a paper disk into agar medium containing test organisms– ____________ ____________ as a failure of an

organism to grow in the region of the antibiotic

Kirby-Bauer Test• 1. ____________ ____________ into plate and

inoculate with test organism• 2. ____________ ____________ ____________

containing known concentrations of antibiotics to the surface

• 3. ____________ plate• 4. ____________ ____________ of zones of inhibition

to a standard table to determine if test organism is susceptible

**If organism is susceptible, it will be killed in patient’s blood stream if experimental concentration of antibiotic is reached

The Disk-Diffusion Method

Antibiotic Resistance and Abuse

• During past 25 years, a large # of bacterial species have evolved with

____________________________________ • ____________ organisms are responsible for human

diseases in:– Intestines, lungs, skin, urinary tract

• Common diseases that used to be easy to treat with a single dose of ____________ are now hard to treat:– Bacterial pneumonia, strep throat, gonorrhea

Antibiotic Resistance and Abuse

• How do MOs ____________ ____________ ?:– Production of ____________ capable of

destroying antibiotic (penicillinase)– Changes in ____________ of cell wall– ____________ to drug’s activity by bypassing a

normal metabolic pathway and creating an altered one (new way to produce folic acid)

Antibiotic Resistance and Abuse

• ____________ ____________ may develop:

– Normally - mutation– From doctors prescribing too many antibiotics –

forced evolution– From hospitals using too high doses of post-

surgery antibiotics – forced evolution– From livestock feeds which contain 40% of all

antibiotics produced in U.S. – forced evolution

Antibiotic Resistance and Abuse

Can resistance be transferred??• Researchers ____________ ____________

antibiotic resistance genes from one bacterial species to another using plasmids

• There is potential for the transfer of antibiotic resistance from a harmless bacterium to a pathogenic bacterium

• Result – ____________ ____________

Antibiotic Resistance and Abuse

• ____________ have been known as miracle drugs – they are overworked miracles

• Suggestions have been made to ____________ their use as strictly as narcotics are controlled

• But, antibiotics are ____________ in 3rd world countries where they are sold over-the-counter