Chemotherapy of infectious disease (antimetabolites) Flashcards
Germ theory
Germ theory of diseases states that microorganisms, known as pathogens, or germs
can lead to disease
Diseases caused by pathogens are called infectious diseases
Types of pathogeen
ESKAPE pathogens
Bacteria: general structure
Bag: capsule, cell wall, plasma membrane
•Contents: cytoplasm, ribosomes, plasmid DNA, nucleoid (cDNA)
•NB: no nucleus
Bacteria: Gram staining
Gram staining classifies bacteria by cell wall type
•Cells are stained with crystal violet
–Gram +ve cells retain the primary stain
–Gram –ve cells primary stain washes out, counterstained (pink)
Gram +ve
thick peptidoglycan layer
cytoplasmic membrane
Gram –ve
•lipopolysaccharide outer
envelope
•thin peptidoglycan layer
•cytoplasmic membrane
Commensal bacteria
–Live on the outer surfaces of our bodies e.g. skin, mucus membranes, gut
–May be beneficial
–May cause serious illness in host or infect another person
–Examples:
•streptococcus – tonsillitis
•Pneumococcus – pneumonia
•Haemophilus influenzaetype B – meningitis
Virulence– ability to cause disease
Virulence factors- molecules produced by bacteria that add to their effectiveness
–Colonization of a niche in the host – includes attachment to cells
–Immunoevasion – evasion of the host’s immune response
–Immunosuppression – inhibition of the host’s immune response
–Entry into and exit out of cells – if the pathogen is intracellular
–Obtain nutrition from the host
Antibacterials: targeting the cell wall
•Cell wall is essential to bacteria survival
- stop synthesis of cell wall
- disrupt cell wall integrity
Peptidoglycan cell wall synthesis
•Gram +ve bacteria •Polysaccharide chains –(NAG-NAM) repeating units •Peptide Chains –connect to 3-OH of NAM –L-Ala-D-Glu-L-Lys-D-Ala-D-Ala •Pentaglycine crosslinks –formed by Transpeptidase enzyme (PBP) –D-Alanine leaving group
Transpeptidase essential for bacterial cell viability
–catalyses crosslinking NAG-NAM chains
–membrane bound protein
–cleaves terminal D-Ala residue
Summary: b-lactams
•Target cell wall biosynthesis •Target transpeptidase enzyme •Affinity labels •Three main classes: –penicillins –cephalosporins –carbapenems •Resistance via b-lactamase –clavulanic acid
Vancomycin
•Branched tricyclic glycosylated non-ribosomal peptide •Usually given IV •Used for serious, life-threatening infections by resistant Gram +ve bacteria