Infectious Disease.docx - Infectious Disease Cell Wall Inhibitors these drugs weaken the cell wall and thereby promote bacterial lysis and death

Infectious Disease.docx - Infectious Disease Cell Wall...

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Infectious DiseaseCell Wall Inhibitors: these drugs weaken the cell wall and thereby promote bacterial lysis and death.Penicillin:oCell Wall: a rigid (prevents expansion or the take up of water), permeable, mesh-like structure that lies outside the cytoplasmic membrane (inside the osmotic pressure is very high). oGenerally bactericidal, only active against bacteria that are undergoinggrowth and division.oWeaken the cell wall by 2 actionsInhibition of transpeptidases and dis-inhibition (activation) of autolysins.Transpeptidases are enzymes critical to cell wall synthesis (giving cell wall its strength)Autolysins are bacterial enzymes that cleave bonds in the cell wall all the break down of cell wall to promote growth and divisionoThese combined results in cell lysis and death.oThe molecular target of penicillin is known as penicillin binding proteins (PBP). These molecules bind to them to produce anti-bacterial effects. They are located on the outer surface of the cytoplasmic membrane. More than 8 are identified. PBP must be present for penicillin’s to work, these drugs work only when bacteria is present.PBP1 and PBP3 are most critical to penicillin’s anti-bacterial effects. oBacterial resistances to Penicillin’s is determined primarily 3 factorsInability of penicillin to reach their target PBPsInactivation of penicillin by bacterial enzymesProduction of PBPs that have a low affinity for penicillin.oGran Negative Cell wall EnvelopeCell wall of gram negative differs from the cell wall of gram positive; because of this difference some penicillin’s are ineffective against gram-negative bacterial.The cell envelope of gram-positive bacteria’s has only 2 layers the cytoplasmic membrane plus a relatively thick cell wall and despite of its thickness the cell wall can be penetrated by penicillin’s giving them an easy access to PBPs on the cytoplasmic membrane as a result penicillin’s are very active against gram-positive organisms.Gram-negative envelopes have 3 layers, the cytoplasmic membrane, a relatively thin cell wall, and an additional outer membrane. Like the gram positive the gram negative can be
easily penetrated by penicillin’s, however the outer membrane is difficult to penetrate only allowing certain penicillin’s to cross the membrane to reach the PBP on the cytoplasmic membrane (ampicillin).oPenicillinase (Beta-Lactamases)Beta-lactamases are enzymes that cleave the beta-lactam ring, rendering penicillin’s and other beta-lactam antibiotics inactive.Bacteria produce a large variety of beta-lactam some are specific to penicillin and some to other beta-lactam antibiotics (cephalosporin’s) that ones that act selectively on penicillin’s are known as Penicillinases.

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