Mol. Micro. Ch. 22 - Antibiotics Part 2

Penicillins resemble what?

D-ala-D-ala

Penicillins inhibit PBPs by doing what?

Covalently forming acyl-enzyme complexes between beta-lactam and nucleophilic serine of PBPs

Penicillins inhibit what process?

Transpeptidation

What is the penicillin derivative that has increased effectiveness against gram (-) bacteria?

Ampicillin

What enzyme degrades penicillins?

Beta-lactamases

What gene encodes for beta-lactamases?

blaZ

Methicillin (beta-lactam) resistance is conferred by what gene?

mecA

What does mecA code for?

Beta-lactam resistant PBP2a

Where is mecA located?

Staphylococcal cassette SCCmec

What is the other class of beta-lactam antibiotics besides penicillins?

Cephalosporins

What are the 4 cephalosporins?

Cephalexin, cefoxitin, ceftriaxone, cefepime

S. aureus can gain mecA-independent resistance to methicillin through a mutation in what gene?

gdpP

What happens to PBPs in gdpP mutants?

They aggregate to a single foci

The protection against beta-lactams provided by gdpP mutants comes at the cost of what?

Decreased cell division

What does vancomycin do?

Noncovalently hydrogen bonds to D-ala-D-ala preventing transpeptidation

What are the 2 types of vancomycin resistance?

VRSA and VISA

Vancomycin resistance from Tn1546 comes from…?

Vancomycin resistant Enterococcus (VRE) plasmid

What is the TCS used in vancomycin resistance? Which is the sensor kinase which is the response regulator?

VanS = Sensor kinase | VanR = Response regulator

What does VanH do?

Convert pyruvate to lactate

What does VanX do?

Cleave D-ala-D-ala

What does VanA do?

Combine D-ala and D-lac

What does VanY do?

Cleave terminal D-ala-D-ala from NAM

What does bacitracin do?

Prevent C55 bactoprenol recycling by inhibiting its dephosphorylation

What does cycloserine do?

Inhibit conversion of L-ala to D-ala AND inhibit synthesis of D-ala-D-ala

Nisin, epidermin, and galidermin belong to what family of antibiotics?

Lantibiotics

What makes lantibiotics unique?

They contain non-proteinaceous amino acids (lanthionine and 3-methyllanthionine)

(T/F) Nisin, epidermin, and galidermin are all bacteriocins.

True

What bacterium is nicin produced from?

Lactococcus lactis

What is the primary and secondary MOA for nisin (and epidermin/galidermin)?

Primary = sequestering Lipid II precursor | Secondary = pore formation

What does daptomycin do?

Form pores in the membrane

Gramicidin does what?

Forms pores as a dimer

What is the characteristic structure of gramicidin?

Cyclic peptide of altering D and L amino acids

What bacterium produces gramicidin?

Bacillus brevis

What are the 2 translation targeting antibiotics?

Rifampin and Actinomycin D

Of the 6 translation targeting antibiotics, which 2 bind to the 30S subunit?

Gentamicin and Doxycycline

What does gentamicin do?

Induce misreading in the 16S rRNA

What does doxycycline do?

Distort the A site

Of the 6 translation targeting antibiotics, which 4 bind to the 50S subunit?

Erythromycin D, Clindamycin, Chloramphenicol, Linezolid

What does erythromycin D do?

Inhibit translocation

What does clindamycin do?

Inhibit translocation

What does chloramphenicol do?

Inhibit peptidyl-transferase activity

What does linezolid do?

Block 70S ribosome assembly

What 2 antibiotics inhibit fatty acid synthesis?

Platensimycin and Platencin

What enzymes do platensimycin and platencin target?

FabH and FabB/F

What antibiotics target topoisomerases?

Quinolones and Fluoroquinolones

What general classes of translation targeting antibiotics bind to the 50S subunit and prevent peptide formation?

Chloramphenicol, macrolides, and lincosamides

What general classes of translation targeting antibiotics bind to the 30S subunit and impar proofreading?

Aminoglycosides

What general classes of translation targeting antibiotics bind to the 30S subunit and block tRNA binding?

Tetracyclines

What are some examples of macrolides?

Azithromycin, clarithromycin, and erythromycin

What are some examples of lincosamides?

Lincomycin, pirlimycin, and clindamycin

What are some examples of aminoglycosides?

Gentamicin, tobramycin, amikacin, plazomicin, streptomycin, neomycin, and paromomycin