BIOL 222 - Lecture 3: Antibiotics and Antibiotic Resistance

antimicrobials

inhibit the growth or destroy microorganisms

antibiotics

kills or inhibits bacteria

selective toxicity

drugs selectively kills or inhibits the growth of microbial targets while causing minimal or no harm to the host

bacteriostatic

causes reversible inhibition of growth

good for healthy patients

allows immune system to kill remaining pathogens

bactericidal

kill target bacteria

good for immunocompromised

narrow spectrum

targets a small subset of microbes

broad spectrum

targets a large subset of microbes

superinfection

secondary infection

antibacterial kills protective (normal) microbiota

dosage

amount of medication given during a certain period of time

route of administration

method to introduce drug to the body

synergistic interactions

2 or more drugs provide better efficacy together than alone

antagonistic interactions

2 or more drugs produce harmful effects

mode of action

way the drug affects microbes on a cellular level

antibiotic targets

essential components or biochemical processes within bacterial cells that antibiotics interfere with to stop bacterial growth or kill the bacteria

cell wall inhibition

blocks steps of peptidoglycan biosynthesis

disrupting this makes the cell susceptible to osmotic lysis

beta-lactam antibiotics

class of cell wall inhibitors

blocks the cross linking of the peptidoglycan layer

penicillin

broken down by pencillinases and beta-lactamases

cephalosporins

same mode of action as penicillins

less susceptible to penicillinases

glycopeptides

another class of cell wall inhibitors

inhibits cell wall biosynthesis

bactericidal

vancomycin

used to treat infections caused by bacteria

usually used for MRSA

plasma membrane inhibition

target the bacterial cell membrane

polymyxins

target the LPS of gram-negative bacteria (disrupt outer and inner membranes in a surfactant like manner)

inhibit DNA function

to interfere with or block essential processes that DNA performs

gyrases

enzyme that catalyzes the supercoiling of DNA

quinolones

a class of broad-spectrum antibiotics that kill bacteria by inhibiting essential enzymes called DNA gyrase and topoisomerase IV, leading to irreversible breaks in bacterial DNA and cell death

fluoroquinolones

a group of broad-spectrum antibiotics used to treat serious bacterial infections by inhibiting bacterial DNA replication

ciprofloxicin

primary antibiotic for a range of organisms

salmonella (gram negative) to Bacilus anthracis (gram positive)

used against multidrug resistant Mycobacterium tuberculosis

inhibit RNA function

blocks RNA polymerase during transcription

rifampin

prevents elongation after initiation

used to treat tuberculosis

inhibit protein synthesis

target ribosomes during protein synthesis

inhibit enzyme function

a molecule that binds to an enzyme and blocks its activity

competitive inhibition

antibiotic mimics normal enzyme substrate

isoniazid

used for treating TB

inhibits an enzyme used to produce part of cell walls

sulpha drugs

inhibit an enzyme used to produce an intermediate in nucleic acid synthesis

inhibit ATP synthase

synthetic antibacterial class

inhibits mycobacterial growth

interferes with function of ATP synthase (leads to reduced ATP production

bedaquiline

synthetic

only used in untreatable tuberculosis infections

antibiotic resistance

microbes evolve mechanisms that protect them from the effects of antimicrobials

innate resistance

microbes resistant to antibiotic due to basic biology

resistance depends on physiology (different species may be resistant to different classes of antibiotics)

NOT normally transferred between bacteria (found on the chromosome)

acquired resistance

microbes acquire a mutation or a new gene that provides resistance to the antibiotic

can be transferred from one cell to another

plasmids

small, circular DNA molecule that is distinct from a cell's chromosomal DNA (contains accessory genes)

horizontal gene transfer (HGT)

it is not sex

only a small number of genes are transferred

genes more unidirectionally (from donor to recipient)

conjugation

horizontal transfer of plasmid from donor to recipient microbe

can spread antibiotic resistance genes

mechanisms of resistance

the biological and genetic processes an organism uses to become unaffected by a drug or therapy

target site modification

alter drug binding site

decreased uptake

prevent drug entry (inhibits accumulation)

antibiotics need pores or channels to enter cells (change membrane composition)

active efflux

remove drug from the cells (prevents accumulation)

change drug structure

inactivate antibiotics by changing their structure (uses enzymes)

target bypass

use alternate metabolic pathways

myobacterium

a type of rod-shaped bacteria characterized by a waxy, lipid-rich outer layer, known as mycolic acid, which makes them resistant to traditional Gram staining and requires an acid-fast stain to be visualized

multidrug resistant microbes

carry one or more resistance mechanisms

multidrug resistant tuberculosis (MDR-TB)

resistant to both isoniazid and rifampin

extensively drug resistant tuberculosis (XDR-TB)

also resistant to fluoroquinolone

directly observed therapy (DOT)

supervised administration of medications

carbapenem-resistant enterobacteriaceae (CRE)

some bacteria in this family are resistant to nearly all antibiotics

carbapenem

beta-lactam antibiotics

carbapenemase

enzyme that breaks antibiotic

colostin

polymyxin antibiotic

used to treat CRE

antimicrobial stewardship

cautious use of antimicrobials (to reduce unnecessary exposure)