Mechanisms of Antimicrobial Action

Disruption of newly synthesized Cell Wall Antimicrobial

Penicillians
Carbapenems Bind penicillin binding proteins (PBP) such as Serine Proteases
and enzymes responsible for peptidoglycan synthesis. Can affect
Cephalosporoins (Neisseria. G) gram positive and negative, but mostly positive.
Cephamycins
Monobactams Only good against gram-negative anearobic bacteria
β- lactam/ β-lactamase inhibitor Binds β-lactamases and prevents enzymatic inactivation of β-
(Clavulanic acid) lactam. Methicillin is a synthetic that won't be deactivated
Vancomycin
Inhibits cross-linkage of peptidoglycan layers (prevents alaline-
alanine bridge between NAM subunits in G positive). Broad
Cycloserine spectrum. Used for C. Difficile and MRSA. Enterococcus resists
heavily Cell Wall Disruption
-Beta-lactams
Bacitracin -Vancomycin
Blocks secretion of peptidoglycan precursors NAG and NAM from
cytoplasm. It also disrupts the cytoplasmic membrane and -Cycloserine
inhibits RNA synthesis -Bacitracin
-Isoniazid
Isoniazid -Ethionamide
Inhibits mycolic acid synthesis. Very good against mycobacterium -Ethambutol
tuberculosis and leprae (And some Gram negatives) Combination -Polymyxin
Ethionamide is part of the cocktail -Daptomycin
Ethambutol
Inhibits arabinogalactan synthesis which is in mycobacterium
tuberculosis. Very good against mycobacterium tuberculosis, and
mycobacterium leprae

Polymyxin (Also see "Disruption of

Cytoplasmic Membranes") Inhibits bacterial membranes (Only gram negatives because of
outer layer making them narrow spectrum)

Daptomycin
Binds irreversibly to cytoplasmic membrane, disrupting ionic
gradients and depolarizing the cell. It cannot penetrate the cell
walls of gram-negatives

Inhibition of Protein Synthesis Antimicrobial

Aminoglycosides
>>Streptomycin
>>Kanamycin Produce premature release of aberrant peptide chains from 30S
>>Gentamicin ribosome (Best against gram negative aerobes and mycobacteria).
>>Tobramycin Best paired with cell wall synthesis inhibitors to treat enterococci.
>>Amikacin They are ototoxic in high enough doses (Toxic to ear) 30S Ribosome
-Aminoglycosides
-Tetracylines
Tetracyclines -Tigecyclin
>>Doxycycline Prevent polypeptide elongation at 30S ribosome right at the
>>Minocycline docking site of the tRNA. Bacteriostatic at low concentrations;
bactericidal at high concentrations. Broad spectrum

Chloramphenicol
Broad spectrum; bacteriostatic. Binds to peptidyl transferase of
50S ribosomal subunit, blocking peptide elongation between
amino acids and carboxyl group

Macrolides
>>Erythromycin (For Actinomyces)
>>Azithromycin
>>Clarithromycin 50S Ribosome
-Chloramphernicol
Prevent polypeptide elongation at 50s ribosome by immobilizing -Macrolides
Stretogramins it -Clindamycin
Ketolides -Linezolid
-Quinupristindalfopristin
Lincosamides -Teltithromycin
>>Clindamycin
Oxazolidinone
Binds to 30S subunit which deforms it, preventing formation of
70S initiation complex and initiation of protein synthesis. Narrow
spectrum against multidrug resisitant bacteria

Inhibition of Nucleic Acid Synthesis Antimicrobial

Quinolones and Fluoroquinolones
(Also see "Antimetabolites") Bind α subunit of topoisomerase II (DNA gyrase). Broad spectrum
Antibiotic. Mycobacterium tuberculosis produces MfpA protein,
which binds to DNA gyrase so the fluoroquinolone won't be able
to
DNA Replication
-Quinolones
-Metronidazole
-Clofazimine
 DNA Replication
Metronidazole -Quinolones
Disrupts bacteria DNA (Is cytotoxic compound) also antiparasite. -Metronidazole
Kills obligate anaerobes. Causes hairy black tongue -Clofazimine

Clofazimine
Rifampin (part of cocktail in
tuberculosis)
Rifabutin
Nucleotide Analogs
>>A - Adenosine arabinoside
>>T - Azidothymidine (AZT)
>>C - Dideoxycytidine (ddC)
>>G - Acyclovir (ACV)
Binds to mycobacterial DNA (Very good against M. tuberculosis
and M. leprae
RNA Synthesis
Prevent transcription by binding DNA-dependent RNA
-Rifampin
polymerase. Good against tuberculosis
-Rifabutin
Reverse Transcriptase
Inhibitors
Act against an enzyme HIV uses in replication. Safe for humans -Adenosine arabinoside
because we don’t have RT. Narrow spectrum -Azidothymidine (AZT)
-Deoxycytidine (ddC)
-Acyclovir (ACV)

Disruption of Cytoplasmic Membrane Antimicrobial

Polyenes
>>Nystatin Attach to ergosterol in fungal membranes. Amphotericin B creates
>>Amphotericin B pore and make membrane leaky

Azoles and Allylamines

>>Fluconazole Inhibit ergosterol synthesis. This is safer for us since we do not
>>Terbinafine synthesize ergosterol. Broad spectrum

Polymyxin Cell Membrane Disruption

-Polyenes
Acts as a detergent on cytoplasmic membranes of gram -Azoles and Allylamines
negatives. Also increases cell permeability, promotes cell death, -Polymyxin
and breaks down lipid moiety of membrane through interaction -Pyrazinamide
w/LPS and phospholipid. Toxic to kidneys -Praziquantel
-Ivermectin
Pyrazinamide
Disrupt transport across cytoplasmic membrane in M.
tuberculosis. Active against intracellular, nonreplicating cells like
M. tuberculosis
Praziquantel Change permeability of cell membranes of several types of
Ivermectin parasitic worms. Narrow spectrum
Inhibition of Metabolic Pathways Antimicrobial
Sulfonamides (converts PABA to DHP
via DHP synth) Compete with p-aminobenzoic acid (PABA); prevents folic acid
synthesis. Inhibits dihydropteroate synthase (1st enzyme in folic
acid synthesis) from making Dihydrofolic acid. Broad spectrum
Antifolates
Dapsone -Sulfonamides
Inhibits dihydropteroate synthase (1st enzyme in folic acid -Dapsone
synthesis) -Trimethoprim
Trimethoprim (DHP to THP via DHP -Para-aminosalcylic acid
Reduct) Inhibits dihydrofolate reductase (2nd enzyme in folic acid
synthesis) from making Tetrahydrofolic acid and disrupts folic acid
synthesis. Paired with sulfonamids is good against UTIs which can
inhibit folic acid synthesis
Quinolones

Interfere with metabolism of malaria parasites

Heavy Metals Inactivate enzymes (Remember Paul Ehrlich in the 1900's)

>>Arsenic Antimetabolites
Flubendazole
>>Mercury -Quinolones
Prevent tubulin polymerization and glucose uptake by protozoa
>>Antimony
Mebendazole and parasitic worms -Heavy Metals
-Flubendazole
Amantadine, -Mebendazole
Rimantadine, Antiviral in Influenza Virus; blocks viral activation by preventing -Amantadine
and weak organic bases viral uncoating via inhibition of protein M1 or M2 (M1 = -Rimantadine
Separates proteins from RNA / M2 = Proton pump).

Antiviral in HIV; HIV uses protease to clip the seal on the coat to
allow virus to be unpackaged. Amantadine inhibits protease

Treatment Combos
Disease Treatment
Tuberculosis Isoniazid + Ethambutol + Rifampin or Streptomycin
UTIs Sulfonamide + Trimethoprim