Bacteria Lectures Flashcards
phase variation
Control of transcription by DNA rearrangement
eg: reversible switching in the synthesis of two alternative flagellar antigens alternation between several antigenic forms of pili expressed on the cell
transposon
discrete segment of DNA which is capable of moving itself (or a copy of itself) from one chromosomal location to a new location within the cell
may transpose and become stabley and permanently integrated into the bacterial chromosome.
Insertion Sequences
(IS elements) are transposons that simply
encode transposase. Play a role in genome evolution by inactivating genes into which they transpose, or turning on expression of adjacent genes.
Complex transposons
carry additional genes such as those encoding
antibiotic resistance, toxins, adhesins and other virulence factors.
F plasmid
prototype self-transmissible plasmid
Autonomous replication of the plasmid DNA
ii. Synthesis of sex pili (F pili) which are essential for mediating pair formation between donor and recipient cells
iii. Conjugative transfer of F DNA to recipient (F-) cells
iv. Ability to integrate into the bacterial chromosome
Conjugative transposons
mobile elements which mediate conjugation
between pairs of cells, in which the transferred DNA is the conjugative transposon itself
Lipopolysaccharides (LPS) of gram negative bacteria
LPS is an example of a pathogen-associated molecular pattern (PAMP) that is recognized by the innate immune system and elicits host responses by a pathway
Toxins that stimulate cytokine production
superantigens are the most potent known T cell activators. They act by binding both to major histocompatibility (MHC) class II molecules on antigen-presenting cells and to specific Vβ chains on T cells at a site that is different from the antigen-binding site, and they activate much larger numbers of T cells than any specific antigen does. Superantigens stimulate excessive production of cytokines (including interleukin-2, interferon gamma, and others), thereby causing pathologic effects.
Shiga toxins of Shigella dysenteriae and E. coli, and the plant toxin ricin
inhibit protein synthesis
inactivating the ribosomes
Diphtheria toxin and Pseudomonas aeruginosa exotoxin A
inhibit protein synthesis
inactivate elongation factor 2 (EF-2)
Toxins that modify intracellular signaling pathways.
Pertussis toxin
Heat-labile enterotoxins of Vibrio cholerae and Escherichia
Anthrax
coli
Toxins that inhibit release of neurotransmitters
Botulinum toxin
Tetanus toxin
Toxins with intracellular targets must cross the plasma membrane before they can exert their toxic effects.
They typically use normal membrane constituents as receptors.
usually enter target cells by endocytosis
β-lactam resistance
β-lactam antibiotics act by irreversibly binding to and inactivating the transpeptidase reaction of penicillin-binding proteins, thereby inhibiting peptide cross-linking and peptidoglycan synthesis
β-lactamases are enzymes that inactivate β-lactam antibiotics by splitting the amide bond of the β-lactam ring, and thereby protect the activity of penicillin binding proteins.
ESBLs (extended spectrum beta-lactamases): can even attack up to 3rd gen cephalosporins
ampC-encoded β-lactamase
Enterobacter, Pseudomonas,
not inhibited by betalactamase inhibitors
The mutational events that lead to permanent high-level expression of ampC can occur during therapy!
Carbapenemases
Klebsiella pneumoniae
hydrolyzes all carbapenems and all other β-lactams
Altered penicillin-binding proteins (PBPs)
When present in S. aureus, it is classified as “methicillin-resistant” S. aureus, otherwise known as MRSA.
Mosaic PBPs : Seen mainly in Streptococcus pneumoniae and Neisseria gonorrhoeae.
Vancomycin resistance
vancomycin prohibits incorporation of the precursor molecule into the pedtidoglycan. This disrupts cell
wall synthesis and leads to cell death.
Vancomycin-resistant enterococci (VRE) - modify target
Staphylococcus: reduced susceptibility to vancomycin
a) Cell walls contain markedly thickened layers of peptidoglycan
b) There is LESS cross-linking of the peptides. This leaves free amino acid chains in the cell wall that still contain the D-alanine – D-alanine terminus, where vancomycin can bind.
Quinolone resistance
target the essential bacterial enzymes DNA gyrase and DNA topoisomerase IV: DNA replication
Quinolone resistance occurs due to one or more nucleotide mutations that result in amino
acid substitutions in a region of GyrA of DNA gyrase, or ParC of topoisomerase IV called the
quinolone-resistance-determining region (QRDR)
reducing the affinity of the enzyme-DNA complex for the quinolone
Resistance to Macrolides
prevents peptide chain elongation.
Modifying the target: Methylation of the ribosome
D test: Isolates harboring either efflux-mediated resistance or inducible ribosomal methylation will
test the same: resistant to macrolides and sensitive to clindamycin
Either the bacterium has an inducible erm methylase system or a macrolide efflux pump system. In
the first case, one would be wary of using clindamycin, because if a mutation occurs in the bacterial
population while treating with clindamycin, that would cause constitutive expression of erm and
resistance to clindamycin. In the second scenario with the efflux pump, clindamycin use should be ok,
as efflux will only act on the macrolide.
If the bacteria in question possesses the inducible erm system, erythromycin will induce resistance to clindamycin and the zone of clearing for clindamycin will be blunted, forming a D-shape of colony growth.
Bottom line is that for organisms harboring erm that
test sensitive to clindamycin, you shouldn’t use EITHER macrolides or clindamycin. If the organism
harbors an efflux pump to macrolides, you shouldn’t use macrolides, but clindamycin is fine.
Select the antibacterial agent that rapidly accumulates in bladder and urine
Nitrofurantoin (Macrobid)
bone
Clindamycin
pulmonary cells
Macrolides
into gingival crevicular fluid and sebum (periodontitis and acne)
Tetracyclines
bind cells of the inner ear and renal brush border ototoxicity and nephrotoxicity
Aminoglycosides
bind Ca++ in developing bone and teeth abnormal bone growth and tooth discoloration
Tetracyclines
causes colitis and pseudomembranes
Clindamycin (Cleocin)
Toxigenic Clostridium difficile selected out during treatment (superinfection, 0.1-10%)
