2D Microbio

Selective toxicity

Ability to kill or inhibit growth of microbes without simultaneously damaging host tissues

Ideal antimicrobial drug

Selectively toxic, microbicidal rather than static, stays potent long enough to act, not subject to antimicrobial resistance, assists host defenses, remains active when diluted in body fluids and tissues, readily delivered to site of infection, reasonably priced, and does not disrupt host health

Microbicidal

Kills microorganisms

Microbiostatic

Inhibits growth of microorganisms without killing them

Antibiotic

Substance produced by the natural metabolic processes of some microorganisms that can inhibit or destroy other microorganisms

Antimicrobial

Umbrella term for any substance that kills or inhibits microbes regardless of source

Difference between antibiotic and antimicrobial

Antibiotics have a natural source while antimicrobials include both natural and laboratory-produced agents

Semisynthetic drug

Drug originally derived from a natural source that has been chemically modified to improve effectiveness

Synthetic drug

Drug entirely synthesized in a laboratory with no natural source

Narrow-spectrum antimicrobial

Effective against a small range of cell types, usually because it targets a specific component found only in certain bacteria

Medium-spectrum antimicrobial

Effective against a wider range of microbes, such as some gram-positive and some gram-negative bacteria, but not all types

Broad-spectrum antimicrobial

Effective against the greatest range of microbes including gram-positive bacteria, gram-negative bacteria, rickettsias, mycoplasmas, and spirochetes

Spectrum of activity

The range of different microorganisms that an antimicrobial drug can affect

Gram-positive bacteria

Bacteria with thick peptidoglycan cell walls that retain crystal violet stain

Gram-negative bacteria

Bacteria with thin peptidoglycan and an outer membrane that do not retain crystal violet stain

Rickettsias

Obligate intracellular bacteria often transmitted by arthropods such as ticks

Mycoplasmas

Bacteria that lack a cell wall

Spirochetes

Spiral-shaped bacteria with flexible cell structures

Selectively toxic antimicrobial

Targets microbial structures or processes that are absent or significantly different in host cells

Most important goal of antimicrobial therapy

Destroy or control microbes while causing minimal harm to the host

Why broad-spectrum drugs can be a disadvantage

They may disrupt normal microbiota and increase risk of secondary infections

Why narrow-spectrum drugs are often preferred

They target specific pathogens and cause less disruption to normal microbiota

Antimicrobial resistance

Ability of microorganisms to survive or grow despite exposure to an antimicrobial drug

Host defenses

Immune system mechanisms that help protect the body from infection

Potency

Strength or effectiveness of a drug at producing its intended effect

Site of infection

Specific location in the body where a pathogen is causing disease

Normal microbiota

Microorganisms that normally live on or in the body and provide beneficial functions

Secondary infection

Infection that occurs because normal microbiota have been disrupted or host defenses weakened

Chemotherapeutic agent

Any chemical used to treat disease by killing or inhibiting pathogens while minimizing damage to the host

Five mechanisms of antimicrobial action

Inhibition of cell wall synthesis, breakdown of cell membrane structure or function, interference with DNA and RNA functions, inhibition of protein synthesis, and blockage of key metabolic pathways

Inhibition of cell wall synthesis

Antimicrobial mechanism that prevents bacteria from building a strong cell wall

Breakdown of cell membrane structure or function

Antimicrobial mechanism that damages the cell membrane, causing leakage and cell death

Interference with DNA and RNA functions

Antimicrobial mechanism that prevents nucleic acid synthesis, replication, or transcription

Inhibition of protein synthesis

Antimicrobial mechanism that prevents ribosomes from making proteins needed for cell survival

Blockage of key metabolic pathways

Antimicrobial mechanism that prevents bacteria from carrying out essential biochemical reactions

Target of cell wall inhibitors

Peptidoglycan in the bacterial cell wall

How cell wall inhibitors work

React with enzymes required for cross-linking glycans in peptidoglycan

Effect of cell wall inhibition

Cell develops weak points, becomes osmotically fragile, and lyses

Why cell wall inhibitors are bactericidal

They cause bacterial cells to rupture and die

Peptidoglycan

Structural component of bacterial cell walls made of glycan chains cross-linked by peptides

Cross-linking glycans

Process that strengthens peptidoglycan and gives the cell wall rigidity

Osmotically fragile

Easily damaged or lysed due to osmotic pressure

Lysis

Rupture and destruction of a cell

Effect of gram-negative outer membrane on cell wall drugs

Outer membrane can prevent drugs from reaching peptidoglycan, making them less effective

Why cell wall drugs work best on young growing cells

Actively growing cells are constantly making new peptidoglycan

Outer membrane

Additional protective layer found in gram-negative bacteria

Cell membrane disrupting antimicrobials

Drugs that damage the bacterial cell membrane causing leakage and death

Why cell membrane drugs can harm host cells

Human cells also have cell membranes, making these drugs less selective

Why cell membrane drugs are less specific

Both bacterial and human cells possess membranes

Target of nucleic acid inhibitors

DNA or RNA synthesis and function

Four ways nucleic acid inhibitors work

Block nucleotide synthesis, inhibit replication, stop transcription, or act as analogs

Blocking nucleotide synthesis

Prevents cells from making the building blocks of DNA and RNA

Inhibiting replication

Prevents DNA from being copied before cell division

Stopping transcription

Prevents DNA from being used to make RNA

Analog

Nonfunctional look-alike of a normal nucleotide base

How analogs work

They are incorporated into nucleic acids but do not function properly

Nucleotide

Basic building block of DNA and RNA

Replication

Process of copying DNA

Transcription

Process of producing RNA from a DNA template

Target of protein synthesis inhibitors

Ribosomes and their associated components

Why protein synthesis inhibitors are selectively toxic

Bacterial ribosomes differ from human ribosomes

50S ribosomal subunit

Large subunit of the bacterial ribosome targeted by some antibiotics

30S ribosomal subunit

Small subunit of the bacterial ribosome targeted by some antibiotics

tRNA

Transfer RNA that carries amino acids to the ribosome during protein synthesis

Ribosome

Cellular structure responsible for protein production

Protein synthesis

Process of assembling amino acids into proteins

Quick memory trick for cell wall inhibitors

No wall equals burst cell

Quick memory trick for cell membrane inhibitors

Membrane leaks and cell dies

Quick memory trick for DNA/RNA inhibitors

No genetic instructions equals no growth or reproduction

Quick memory trick for protein synthesis inhibitors

No proteins equals no cell function

Quick memory trick for metabolic pathway inhibitors

No metabolism equals no survival

Most important target unique to bacteria

Peptidoglycan cell wall

Most important target shared with humans

Cell membrane

Most common structure targeted by protein synthesis drugs

Bacterial 30S and 50S ribosomal subunits

Competitive inhibition

Process in which a drug mimics the normal substrate of an enzyme and takes its place

Metabolic analog

Drug that resembles a normal substrate and competes for an enzyme's active site

How metabolic pathway inhibitors work

Use competitive inhibition to block essential bacterial metabolic reactions

Bacterial metabolic pathway target discussed

Folic acid synthesis

Why folic acid synthesis is a good drug target

Mammals do not possess this enzyme system, making it selectively toxic to bacteria

Folic acid synthesis inhibitor

Antimicrobial that prevents bacteria from making folic acid needed for growth and DNA production

Beta-lactam drugs

Group of cell wall inhibitors that contain a beta-lactam ring

Non-beta-lactam drugs

Cell wall inhibitors that do not contain a beta-lactam ring

Beta-lactam ring

Highly reactive ring structure composed of 3 carbons and 1 nitrogen

Function of the beta-lactam ring

Interferes with proteins involved in cell wall synthesis, leading to lysis and cell death

Effect of beta-lactam drugs

Prevent proper peptidoglycan formation causing bacterial cell lysis

Major beta-lactam drug groups

Penicillins, Cephalosporins, Carbapenems, and Monobactams

Most common antimicrobial class

Beta-lactams make up more than half of all antimicrobic drugs

Penicillins

Group of beta-lactam antibiotics named after the parent compound and usually ending in -cillin

Suffix for penicillin drugs

-cillin

Natural source of penicillin

Penicillium chrysogenum

Penicillium chrysogenum

Fungus that naturally produces penicillin

Penicillinase

Enzyme that hydrolyzes penicillin and is found in penicillin-resistant bacteria

How penicillinase causes resistance

Breaks down penicillin before it can affect the bacterial cell wall

Beta-lactamase

Enzyme secreted by some bacteria that breaks open the beta-lactam ring

How beta-lactamase causes resistance

Cleaves the beta-lactam ring, inactivating penicillins and cephalosporins

Difference between penicillinase and beta-lactamase

Penicillinase specifically destroys penicillin while beta-lactamase destroys beta-lactam drugs by breaking the beta-lactam ring

Penicillinase-sensitive antibiotic

Antibiotic that can be destroyed by penicillinase

Beta-lactamase-sensitive antibiotic

Antibiotic that can be destroyed by beta-lactamase

Penicillinase-resistant antibiotic

Antibiotic that is not affected by penicillinase

Beta-lactamase-resistant antibiotic

Antibiotic that is not affected by beta-lactamase