Glossary of Bacteriology lecture 09 Antibiotics that affect cell wall synthesis

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Which bacteria do not possess a peptidogylcan layer
The mycoplasma, certain marine halophiles, and stable mutants that lack a peptidoglycan (L-forms)
What is the basic structural unit of murein from Staphylococcus aureus
Repeating disaccharide of Beta-1,4 linked MurNac and GlcNac
What are the structural features of murein
The MurNac GlcNac dissacharide; a tetrapeptide; crosslinking between the glycan strands; variation in the amino acids at position 2 and 3 and the nature of the crosslink
What is a park nucleotide
A Muramic Acid attached to UDP and a peptide. Free -NH2 and-COOH on lysine and alanine, and one extra alanine per muramic acid
What is the mechanism of action of Fosfomycin
Fosfomycin is a structural analog of phosphoenolpyruvate (PEP), and the drug becomes covalently-linked to the active site of the pyruvyl transferase
What are the characteristics of Fosfomycin
Broad spectrum, bactericidal antibiotic. Prevents synthesis of UDP-MurNac. Resistance emerges with high frequency
What is unique about the synthesis of the UDP-MurNac-Pentapeptide
It does not involve ribosomes, tRNA, mRNA, or other components of the protein synthesis machinery
In gram positive bacteria, what is the third amino acid in the UDP-MurNac-Pentapeptide
Lysine. In gram negative it is diaminopimelic acid (DAP)
What does D-cycloserine inhibit
Synthesis of D-alanine and ligation of two C-Ala residues to form dipeptide.
What are the characteristics of D-cycloserine
It is a structural analog of D-alanine. It is a competive inhibitor of both alanine racemase and D-alanine ligase. It is a broad spectrum, bacteriostatic drug, but frequently causes neurotoxic side effects
What is the initial reaction in the membrane bound phase of the biosynthetic sequence
Transfer of MurNac-pentapeptide-monophosphate from UDP-MurNac-pentapeptide to a glycosyl carrier lipid (GCL)
What are the characteristics of Vancomycin
Inhibits the transglycosylase step by binding tightly to the D-alanyl-D-alanine residues on the pentapeptide. This prevents binding to the synthetase. Bactericidal used primarily for the treatment of infections caused by staphylococci and enterococci
What does bacitracin inhibit
Regeneration of GCL-P from GCL-PP. It binds tightly and prevents dephosphorylation. Bactericidal against gram positive organisms
What do Beta-lactam antibiotics block
Transpeptidation (cross-linking of the peptidoglycan)
During normal transpeptidation, what is lost
The carboxyl-terminal D-alanine. The reaction is energetically neutral
What are the most well-known Beta-lactam antibiotics
Penicillins, Cephalosporins, and Cephamycins. Others include the carbapenems and the monobactams
What are the two rings that make up penicillins
A Beta-lactam ring and a Thiazolidine ring
What are B-lactam antibiotics used together with
B-lactamase inhibitors, which prevent destruction of the B-lactam antibiotic
What are B-lactam antibiotics substrate analogs of
The terminal D-ala-D-ala-COOH region of the pentapeptide. They inhibit transpeptidases and also D,D-carboxypeptidases
What type of drugs are the penicillins and cephalosporins
Bactericidal drugs that require actively growing cells in order for them to be effective
What are penicillin-binding proteins (PBPs)
The building of the chains and cross links is catalyzed by specific enzymes (transpeptidases, transglycosylases, carboxypeptidases) that are members of a large family of serine proteases, called PBPs
How many PBPs does E. coli have
Eight (1A, 1B[alpha, beta, gamma], 2,3,4,5,6,7)
What is the killing target of mecillinam
What will inhibition of transpeptidation by Beta-lactam antibiotics cause
Amplification of the effect of autolytic enzyme activity that will result in cell lysis
What steps in the pathway of murein synthesis occur following translocation of intermediates to the outer face of the cytoplasmic membrane
The GlcNac MurNac dissacharide is attached to the chain by transglycolylases. Transpeptidases cause cross-linking
Do all Beta-lactam antibiotics have the same spectrum of activity
No. Individual PBPs have different function (cell-elongation, formation of rod shape, formation of septa), and so they also vary in their sensitivity to specific Beta-lactam antibiotics

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