JMU microbiology exam 3

Drug resistance

Microbes are able to tolerate exposure to a drug they were once susceptible to

Drug resistance: Drug inactivation

Production of enzymes that destroy/ alter drug, Hydrolze the beta-lactam ring of penicillin and cephalosporins

Penecillin

• any drug ending in “cillin" , source= Penecillium chrysogenum → produces 100X more than original strain.

• penicillin G (narrow spectrum, g+ targets, unstable in stomach acid), penicillin V (can withstand stomach acid), other: amoxicillin + ampicillin (semi-synthetic, different side chains, g -, move across outer membrane)

Penicillin structure

1. Beta-lactam ring

2. Thiazolidine ring

3. Variable side chain

Drug resistance: permeability/ uptake

• keep drug out of cell, multidrug resistance pumps (MDR) transport drugs/chemicals out of cell. Located in the cell membrane

• proteins encoded either in the chromosome or on a plasmid, not selective, effects lots of pathogens (G+ and G-)

Drug resistance: change in binding site

• mutation in ribosomal proteins, or attaches to ribosome to prevent protein synthesis

• ex: Erythromycin- macrolide, moderate spectrum, low toxicity, blocks protein synthesis

Erythromycin use

administered for chlamydia, mycoplasma pneumonia, legionellosis, pertussis (whooping cough), diphtheria, acne

Syphillis

• Transmission: oral, vaginal, anal, congential

• caused by Treponema palladium

• 4 stages

Stages of Syphilis

1. Primary: sore at sight of infection

2. Secondary: skin rash, swollen lymph nodes, fever

3. Latent: so signs/symptoms

4. Tertiary: severe symptoms- neurological, cardiac, skin. (3-16 years after infection, 1/3 of cases reach this stage)

Congenital syphillis

• still birth, low birth weight, seizures, cataracts, deafness, death

• # of babies born in U.S. has doubled in 2013-17

• easily preventable

Drug resistance: metabolism

• metabolic pathway change

• Sulfonamide and Trimethoprim: alternative synthesis of folic acid

Why is drug resistance growing

• human usage/ distribution

• inappropriate use

Antibiotic stewardship

proper use, keep effectiveness and extend lifespan of antibiotics, protect people from antibiotic resistant infections

Agricultural antibiotics

• crop productivity, treat sick animals or act as growth promoters

• animal waste is important resistant bacteria, contaminated soil + water + food

Clostridium difficile

• urgent threat of antibiotic resistance

• life threatening, problematic for hospital methods,diarrhea (10x a day)+ colon infection

• 500,000 infections + 15,000 deaths each year

Carpabenem-resistant enterobacteriae (family)

• urgent threat of antibiotic resistance, nightmare bacteria

• Klebsiella and E coli

• present in long term facilities, most healthy people okay

Neissa gonorheae

• urgent threat of antibiotic resistance “our greatest fear”

• cases rising 30%, 2013-17

Antibiotic side effects

1. damage to tissue through toxicity

2. allergic reaction

3. Disruption of normal flora

Potential toxicity of side effects

• liver damage: metabolize foreign chemicals

• intestinal irritation: diarrhea due to irritation or colitis

• Cardiac: anti parasitic medication causing irregular heartbeat/ arrest

• neurotoxicity: seizures, nerve damage (deaf/dizzines), respiratory failure

• skin: photodermatitis, tooth enamel

Allergy

• when a drug acts as an antigen and stimulates immune system

• either of drug itself of byproduct of this metabolism

• Penicillin has the greatest number of reactions

collateral damage

• when normal flora are killed by broad spectrum drugs

• can cause secondary infection

How to choose the correct drug

1. what microbe is causing infection

2. what is it susceptible to

3. condition of patient

Decontamination

• removal of microbial contaminants 

• methods: heat, radiation, antiseptics, disinfectants

Easiest microbes to get rid of

bacterial vegetative cells, enveloped viruses, yeast, fungal spores, protozoan trophozoites

Moderately difficult microbes to get rid of

protozoan cysts, fungal sexual spores, makes viruses, unique vegetative bacteria

Most difficult microbes to get rid of

bacterial endospores and prions

Sterilization

Process that destroys/removes all viable microbes, nonliving surfaces, usually preformed with heat

bactericide

a chemical agent that kills bacteria

Fungicide

a chemical agent that kills fungi

Viruside

a chemical agent that kills viruses

Sporicide

a chemical agent that kills bacterial endospores

bacteriostatic

inhibition of bacterial growth, doesn’t necessarily kill bacterial cells

Microbiostatic

inhibition of microbial growth

germicide

• any chemical agent that kills pathogenic microbes

• used on living/nonliving tissue, not effective against resistant organisms

disinfectant

• physical process/ chemical agent that destroys vegetative pathogens

• non living tissue, no endospores, gets rid of toxins produces by pathogens

Antiseptic

chemical agent that can be applied to destroy vegetative pathogens

sepsis

infection of blood and other tissues

microbial load

microbial population size

Sanitization

cleansing technique that removes debris, toxins, etc. includes soaps and reduces possible spoiling

degermination

reduce load of microbes (alcohol swabs)

Dead microbe

permanent loss to reproduce

Cell Death Curve

• logarhythic, 10x reduction

• not every cell dies at once, younger cells die first

• sterilization: point where survival is not likely

effects on cell death curve

• microbial load

• agent mode of action

• bacteriostatic vs. bacteriocidal

• spores vs. vegetative cells

Modes of action: cell wall

• prevents cell wall synthesis

• digest cell wall

• break down wall surface

• cells become fragile and lyse

• ex: penicillin, detergents, alcohol

Mode of action: cell membrane

• lowers surface tension of membrane, allows leaks

• lose ability to stop harmful molecules from entering or bringing in essential nutrients

• ex: surfactants, alcohol

Mode of action: protein/ nucleic acids

• bind to ribosome, blocks transcription

• cells can’t make proteins, DNA can’t be replicated

• ex: some antibiotics, radiation

Mode of action: protein function

• denatures proteins breaks bonds in secondary and tertiary structure

• stops metabolism

• ex: heat, organic solvents, metals

Heat

• Moist: 60-135C, denatures proteins and nucleic acids

• Dry: 160-1000C, denatures proteins, oxidizes