Antibiotics Flashcards
Antibiotic modes of action (3)
- Bacteriostatic
- Bacteriocidal
- Bacteriolytic
Bacteriostatic
Total cell count and viable cell count remain the same
Bacteriocidal
Total cell count remains the same but viable cell count decreases
Bacteriolytic
Total cell count and viable cell count both decrease
Cell wall synthesis ABs
Cycloserine Penicillin Carbapenems Cephalosporins Bacitracin Vancomycin Monobactams
Folic acid ABs
Trimethoprim
Sulfonamides
Cytoplasmic membrane structure ABs
Polymyxins
Daptomycin
Lipid biosynthesis ABs
Plantensymicin
Protein synthesis ABs (tRNA)
Mupirocin
Puromycin
30S inhibitors ABs
Tetracyclines Spectinomycin Streptomycin Gentamycin Kanamycin Amikacin Nitrofurans
50S inhibitors ABs
Erythromycin (macrolides)
Chloramphenicol
Clindamycin
Lincomycin
RNA polymerase ABs
Rifampin
Streptovaricins
RNA elongation ABs
Actinomycin
DNA gyrase ABs
Quinolones: Nalidixic acid, Ciprofloxacin, Novobiocin
Macrolide structure
12-16 membered macrolactone ring with various amino sugars
What do macrolides do
Inhibit the 50S subunit of the ribosome
In the 50s subunit
Macrolides bind to a specific site in the upper part of the peptide exit tunnel
What effect does macrolide binding have
Inhibition of translation (peptides can’t exit tunnel)
What do fluoroquinolones do
Target DNA gyrase
Which kinds of DNA gyrase do fluoroquinolones target
Topoisomerase II and IV
Fluoroquinolones are particularly effective against
Gram positive bacteria
Fluoroquinolones enter Gram negative bacteria through
Outer membrane porins
Fluoroquinolones enter Gram positive bacteria by
Passive diffusion
Newer fluoroquinolones have a
Broader spectrum and better activity against Gram positive
Fluoroquinolones are the
Second most used antibiotic
A synthetic antimicrobial
Fluoroquinolones
Fluoroquinones include
Nalidixic acid
Ciprofloxacin
Novobiocin
Cephalosporins are
Semi synthetic beta lactam antibiotics related to penicillin
Cephalosporins are derived from
Cephalosporium (fungus)
Beta lactam antibiotics interfere with
Bacterial cell wall synthesis
Peptidoglycan is made up of
alternating residues of β-(1,4) linked N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)
Beta lactam antibiotics bind to
Transpeptidase enzymes that normally catalyze linkage of the glycan chains (where new tetrapeptides have been inserted)
Binding stops this activity
New ABs inhibit
a broad range of targets including: topoisomerase protein synthesis cell membranes cell wall
Beta lactamase inhibitors
Overcome inactivation of beta lactam antibiotics
Phage are
Natural antimicrobials
Stages of phage infection (5)
- Adsorption to a specific receptor
- DNA injection
- Redirection of host metabolism to phage replication
- Assembly and packing of phage particles
- Bacterial cell lysis and progeny release
Phage attachment is
Highly specific
Peptidoglycan and pore formation by lytic phage allows
Phage DNA injection
Phage late proteins include
Lysins, Holins, Murein synthesis inhibitors
Phage late proteins are responsible for
Host cell lysis
Lytic phage advantages
Cheap
Specific
Lytic phage disadvantages
Narrow spectrum
Rapid resistance
Alternative phage strategies use
Phage to deliver a protein that interferes with an essential bacterial process
Alternative phage strategies cause
Bacterial to be more susceptible to ABs
Phage therapy can be combined with
CRISPR
Anti Virulence Strategies
Inhibit specific mechanisms that promote infection
Anti virulence strategies offer
Reduced selection pressure for drug resistant mutation
Virulence specific drugs are good because
They do not cause the dramatic alteration in host microbiota that ABs do
UPEC
Uro pathogenic E.coli
Mechanism of UPEC infection (5)
- Binding to Facet cells
- Invasion and replication in cells
- Biofilm formation (IBC)
- Biomass dispersion and cell exit
- Spread of infection
IBC
Intracellular bacterial community
UPEC in anti virulence strategies (2)
- Pilicides
Pilus binds to uroplakin on facet cells - no pili=no binding - Creation of analogs to interrupt mediation of binding to the natural receptor
Quorum sensing
Bacterial communication
Quorum sensing controls
A range of phenotypes including virulence factors
Inhibiting quorum sensing with a reporter upstream of a quorum sensing gene
Can result in virulence genes being switched off
Reporter genes can be used to monitor
The levels of expression of another gene
Targeting toxin production in anti virulence strategies
Toxin production is tightly regulated
Virstatin inhibits transcription of cholera toxin
Virstatin
Allows targeting of a specific operon that produces cholera toxin
Receptor mimics in anti virulence strategies
Mop up the toxin, stronger affinity so no binding to host receptor
Protein secretion systems in anti virulence
Bacteria need to get proteins to the cell wall
Molecular needles that inject effector molecules into host cell membranes
Very specific host cell pathogens
Knocking out secretion systems reduce virulence
Faecal extracts inhibit the invasiveness of
Salmonella
The human gut metabolome
Has anti virulence activity
Type III secretion systems produce
Effectors that cause disease (actin rearrangment etc)
Synergistic drug usage causes problems because
Killing off susceptible bacteria removes competition and allows multi drug resistant bacteria to proliferate
