Microbiology-Chapter 20

Front 1

Antimicrobial Drugs

Back 1

-Chemotherapy: the use of drugs to treat a disease

-Antimicrobial drugs: interfere with the growth of microbes within a host

-Antibiotic: a substance produced by a microbe that, in small amounts, inhibits another microbe

-Selective toxicity: a drug that kills harmful microbes without damaging the host

Front 2

History of Chemotherapy

Back 2

1928: Fleming discovered penicillin, produced by Penicillium

1940: Howard Florey and Ernst Chain performed first clinical trials of penicillin

Front 3

The Spectrum of Antimicrobial Activity

Back 3

-Broad spectrum: treats a lot

-Narrow spectrum: treats little

-Superinfections may result when normal flora are disrupted

Front 4

The Action of Antimicrobial Drugs

Back 4

Bactericidal
-kills microbes directly

Bacteriostatic
-prevent microbes from growing

Front 5

The Inhibition of Protein Synthesis by Antibiotics

Back 5

Chloramphenicol
-binds to 50S portion and inhibits formation of peptide bond

Tetracyclines
-interfere with attachment of tRNA to mRNA-ribsome complex

Streptomycin
-changes shape of 30S portion, causing code on mRNA to be read incorrectly

Front 6

B-Lactam Antibiotics
^(beta)

Back 6

Penicillin
-penicillinase-resistant penicillins
-penicillins + B-lactamase inhibitors

Carbapenems
-substitute a C for a S, add a double bond

Monobactam
-single ring

Front 7

Competitive Inhibitors

Back 7

Sulfonamides (sulfa drugs)
-inhibit folic acid synthesis
-broad spectrum
-when use in combination with trimethoprim synergism results

Front 8

Effects of Combinations of Drugs

Back 8

-Synergism occurs when the effect of two drugs together is greater than the effect of either alone

-Antagonism occurs when the effect of two drugs together is less than the effect of either alone

Front 9

Antiviral Drugs

Back 9

-Nucleoside and nucleotide analogs

Front 10

Antiviral Drugs: Modes of Action

Back 10

Inhibit attachment
-block CCR5: HIV

Inhibit uncoating
-Amantadine: Influenza

Inhibit nuclei acid synthesis
-Nucleotide analogs
-->Acyclovir, nucleotide analog, herpesviruses
-->AZT, thymine analog, HIV
-->Reverse transcriptase inhibitors, HIV

Prevent maturation and release
-protease inhibitors, HIV

Front 11

HIV: Human Immunodeficiency Virus

Back 11

Acquired immunodeficiency syndrome

Retrovirus, genus Lentivirus
-use reverse transcriptase to make double stranded DNA from the single-stranded RNA genome
-Viral genes permanently integrated into host DNA

HIV can only infect host cells taht have the required CD4 marker plus a coreceptor

Front 12

HIV Epidemiology

Back 12

-First nationally notifiable in 1984

-6th most common cause of death among people aged 25-44 years in the US

-In 2007, the number of infected individuals worldwide is estimated to be 33 million with ~1.2 million in the US

Front 13

HIV Transmission

Back 13

Transmission
-sexual intercourse
-transfer of blood or blood products
-babies can be infected before or during birth, and from breast feeding
-->20% of infants born to infected mothers are HIV+

HIV does not surive long outside the body

Some individuals are resistant to HIV infection due to mutations in CCR5

Front 14

Pathogenesis of HIV

Back 14

1. HIV enters through mucous membrane or skin and travels to dendritic phagocytes beneath the epithelium, multiplies and is shed

2. Virus is taken up and amplified by macrophages in the skin, lymp organs, bone marrow, and blood

3. HIV attaches to CD4 and coreceptor; HIV fuses with cell membrane

4. Reverse transcriptase makes a DNA copy of RNA

5. Viral DNA is integrated into host chromosome (provirus)

6. Can produce a lytic infection or remain latent

Front 15

Signs and Symptoms in the Stages of HIV Infections and AIDS

Back 15

1. Initial infection: mononucleosis-like symptoms that soon disappear

2. Antibodies are detectable 8-16 weeks after infection

3. Asymptomatic phase 2-15 years (avg. 10)

4. AIDS Symptoms:
-T4 cell levels fall below 200/uL
-fever, swollen lymph nodes, diarrhea, weight loss, neurological symptoms, opportunistic infections and cancers

Front 16

Preventing and Treating HIV

Back 16

Prevention
-monogamous sexual relationships
-condoms
-universal precautions

Therapies
-inhibit viral enzymes: reverse transcriptase, protease, and integrase
-inhibit fusion
-inhibit viral translation
-highly active anti-retroviral therapy

Front 17

Antibiotic Resistance

Back 17

-A variety of mutations can lead to antibiotic resistance

-Mechanisms of antibiotic resistance
1. Enzymatic destruction of drug
2. Prevention of penetration of drug
3. Alteration of drug's target site
4. Rapid ejection of the drug

-Resistance genes are often on plasmids or transposons that can be transferred between bacteria

Front 18

Antibiotic Resistance

Back 18

Misuse of antibiotics selects for resistance mutants. Misuse includes:
-using outdated or weak antibiotics
-using antibiotics for the common cold and other inappropriate conditions
-using antibiotics in animal feed
-failing complete the prescribed regimen
-using someone else's leftover prescription

Front 19

5 Actions of Antimicrobial Drugs

Back 19

1. Inhibition of cell wall synthesis: penicillins, cephalosporins, bacitracin, vanocomycin

2. Inhibition of protein synthesis: chloramphenicol, erythromycin, tetracyclines, streptomycin

3. Inhibition of nucleic acid replication and transcription: quinolones, rifampin

4. Injury to plasma membrane: polymyxin B

5. Inhibition of synthesis of esssential metabolites: sulfanilamide, trimethoprim

Front 20

Methods of Drug Action that Inhibit Protein Synthesis

Back 20

Choloramphenicol
-binds to 50S portion and inhibits formation of peptide bond

Tetracyclines
-interfere with attachment of tRNA to mRNA- ribsome complex

Streptomycin
-changes shape of 30S portion, causing code on mRNA to be read incorrectly

Front 21

**REVIEW QUESTION**

List top 4 "hardest to kill" microbes

Back 21

1. prions
2. endospores
3. mycobacteria
4. protozoan cysts

Front 22

**REVIEW QUESTION**

Explain Quorum Sensing

Back 22

??