Antibiotic Resistance Flashcards
1
Q
What are antibiotics
A
- Naturally produced chemicals / antimicrobial agents, produced naturally by bacteria and fungi that act against other microorganisms
- “Magic Bullets”, kill infection without significantly harming the host
- The presence of antibiotics puts a strong selective pressure onto bacteria
2
Q
What is antibiotic resistance
A
- Select for chromosomal mutations conferring resistance
- Transferred vertically to subsequent microbial generations, eventually predominant in a microbial population that is repeatedly exposed to antimicrobial
- Many genes responsible for drug resistance are found on plasmids or in transposons that can be transferred easily between microbes through horizontal gene transfer
- Transposons also have the ability to move resistance genes between plasmids and chromosomes to further promote the spread of resistance
3
Q
Why is antibiotic resistance increasing
A
- Increased usage of antibiotics (using antibiotics in animal feed)
- Improper prescription of antibiotics (use for viral infections / inappropriate conditions)
- Poor hygiene, sanitation, lack of herd immunity
- Sub-therapeutic dosage
- Patient non compliance with the recommended course of treatment (failing to complete the prescribed regimen, using someone else’s leftover prescription, using outdated or weakened antibiotics)
- Any use of antibiotics selects for resistance = ↑ number of resistant bacteria in any bacterial population
- 20-50% of antibiotic usage is unnecessary
4
Q
What are the consequences of antibiotic resistance and how can it be minimised
A
- Prolongs infections, increases recovery time, increases length and duration of hospital stays & healthcare costs
- Need more expensive and less effective & sometimes more toxic antibiotics to clear infection
- Antibiotic-resistant genes present in nearly every population, physicians cannot use the same antibiotic for long
- Minimised by using antibiotics correctly and only when needed, resistance to a certain antibiotic can be lost if antibiotic is not used for several years
5
Q
What is cross resistance vs multiple resistance vs resistance
A
Cross:
- Single mechanism, closely related antibiotics are rendered ineffective
- Having an efflux pump that can export multiple antimicrobial drugs is a common way for microbes to be resistant to multiple drugs by using a single resistance mechanism
Multiple:
- Multiple mechanisms, unrelated antibiotics, acquire multiple plasmids, major clinical problem
Resistance:
- New mutation or gene transfer (acquisition of a plasmid), provides a selective advantage
6
Q
List the 4 mechanisms of antibiotic resistance and their targets
A
- Targets: Cell wall biosynthesis enzymes and substrates, bacterial protein synthesis and bacterial nucleic acid production and repair
- Mechanisms: Prevention of drug penetration, enzymatic inactivation of drug, efflux pumps and alteration to target site
7
Q
Describe prevention of penetration
A
- Gram negative bacteria are more resistant to antibiotics because of the nature of their cell wall, restricts entry of many molecules through special openings called porins
- Change one amino acid, one nucleotide
- Some bacterial mutants modify a porin opening so antibiotics are unable to enter the peri-plasmic space
- Some bacterial mutants have beta-lactamases in the peri-plasmic space
8
Q
Describe enzymatic destruction
A
- Destruction or inactivation of antibiotics by enzymes (lactamase) that are natural products (penicillins, cephalosporins, carbapenems - all share beta-lactam ring)
9
Q
Describe alterations to target site
A
- Mode of action that inhibits protein synthesis, minor modifications can neutralise effects of antibiotics without significantly affecting cellular function.
- Binding proteins (modify penicillin binding protein)
- Ribosome subunits (resistance to macrolides, tetracyclines, aminoglycosides)
- Lipopolysaccharide structure (resistance to polymyxin)
- RNA polymerase (resistance to rifampin)
- DNA gyrase (resistance to fluoroquinolones)
- Metabolic enzymes (resistance to sulfa drugs, trimethoprim)
- Peptidoglycan subunit peptide chains (resistance to glycopeptides)
10
Q
Describe the efflux pump
A
- Certain proteins in the plasma membranes of gram-negative bacteria act as pumps that expel antibiotics, preventing them from accumulating and reaching an effective concentration
- Bacteria normally have efflux pumps to remove toxic substances, first identified with tetracycline
11
Q
What is the main factor for the outcome of infection
A
- Must have a specific interaction / receptor between host cell and microbe
12
Q
What determines the outcome of infection (4)
A
- Portals of Entry: Mucous membranes (respiratory, gastrointestinal, genitourinary tracts and conjunctiva), skin or parenteral route (direct access to tissues)
- . Evasion of Host Defences: Capsules, cell wall components, enzymes, antigenic variation, invasions and intracellular growth
- Damage to Host Cells: Siderophores, direct damage, toxins (exo vs endo), lysogenic conversion or cytopathic effects
- Portals of Exit: Mucous membranes, skin or parenteral route, or sneezing, coughing and insect bites
13
Q
What is pathogenicity vs virulence
A
- Pathogenicity: Ability to cause disease
Virulence: - Relative ability of a pathogen to cause disease
- Degree of pathogenicity by bacteria and viruses (avirulent to highly virulent)
- ID50: Infectious dose for 50% of a sample population, measures virulence of a microbe (skin - 10-50 endospores, inhalation - 10,000-20,000 endospores)
- LD50: Lethal dose for 50% of a sample population, measures potency of a toxin
- Highly virulent pathogens show little difference in number of cells required to kill 100% of population compared to 50%
14
Q
Define primary vs opportunistic pathogen and compromised hosts
A
- Primary: Cause disease in a host regardless of host’s resident microbiota or immune system
- Opportunistic: Only cause disease in situations that compromise host’s defences
- Compromised Host: The pathogen-host interaction is dependent upon both host and pathogen, certain medical procedures or underlying conditions predispose individuals to develop diseases
- Nosocomial, viral or opportunistic infections (do not cause disease in healthy hosts)
15
Q
List the 4 stages of pathogenesis
A
- Exposure (contact)
- Adhesion (colonisation)
- Invasion
- Infection
- Pathogen must be able to gain entry to host, travel to location where it can establish an infection, evade host’s immune response and cause damage (disease)
