MOA OF ANTIBIOTICS

Inhibitors of Cell Wall synthesis

Inhibitors of Protein synthesis

Inhibitors of Nucleic acid synthesis

Inhibitors of microbial Cell membranes

MOA OF ANTIBIOTICS

Antifungals especially polyenes, antibiotics, polymyxin

Inhibitors of microbial Cell membranes:

Actinomycin, griseofulvin

Inhibitors of Nucleic acid synthesis:

— (50S) Chloramphenicol, Macrolides and Lincosamides

— ( 30S) Aminoglycoside and Tetracycline

Inhibitors of Protein synthesis:

Penicillins, Cephalosporins, Monobactams, Carbapenems, Vancomycin, Bacitracin

Inhibitors of Cell Wall synthesis

Empiric therapy

This is done by giving Broad Spectrum Antibiotic but superinfection must be managed and monitored

CONJUGATION

TRANSFORMATION

TRANSDUCTION

DNA TRANSFER PROCESSES:

TRANSDUCTION

Mediated with the help of bacteriophage that is defined as viruses that infect bacteria.

bacteriophage

defined as viruses that infect bacteria.

TRANSDUCTION

The resistant gene will be acquired by the virus upon infection

TRANSFORMATION

Plasmid circular will transform size and shapes to strands that will penetrate another microorganism transferring the resistant gene

Plasmid circular

will transform size and shapes to strands that will penetrate another microorganism transferring the resistant gene

CONJUGATION

Plasmid- extrachromosomal DNA in bacteria responsible for drug resistance (self-replicating)

CONJUGATION

This plasmid is transferred to another bacteria via this process through sex pilus/pili in which the resistant gene passes through when bacteria interacts with each other transferring the drug resistance

Plasmid

extrachromosomal DNA in bacteria responsible for drug resistance (self-replicating)

sex pilus/pili

This plasmid is transferred to another bacteria via this process through ______ in which the resistant gene passes through when bacteria interacts with each other transferring the drug resistance

Mutation of Cellular Targets

Decreased Uptake

Inactivation of Drug

Increased Efflux

Altered Expression Of Proteins In Drug-Resistant Organisms

Increased Efflux

pumps are activated excreting the drug off the cell

Inactivation of Drug

some bacteria are capable of producing enzymes that can destroy the drug

Decreased Uptake

different layers in the bacteria can form new walls using proteins caused by mutation resulting to a decreased penetration of the drug → decreased action

Mutation of Cellular Targets

The result of mutation is still a protein (transcription → RNA → protein translation process) that will cause the loss of cellular target of the drug since new protein is formed

BETA LACTAMS

Cyclic amide with four atoms in its ring

BETA LACTAMS

The active component of penicillin (also seen in cephalosporin, carbapenem, and monobactam)

CEPHALOSPORIN

BETA LACTAMS

When fused with 6-membered dihydrothiazine ring

PENICILLIN

BETA LACTAMS

5-membered thiazolidine ring, it produces

D-Ala-D-Ala peptide sequence

Beta Lactam ring mimics the shape of the terminal

D-Ala-D-Ala peptide sequence

that serves as the substrate for cell wall transpeptidases that form covalent bonds between different peptidoglycan chains during periods of cell growth.

N-acetylmuramic acid (NAM) and

N-acetylglucosamine (NAG)

Peptidoglycan Layer (Wall of Bacteria)

Composed of

Alexander Fleming (1928)

Discovered Penicillium notatum (Penicillin)

Penicillium notatum (Penicillin)

○ First antibiotic agent

○ Serendipity (accidentally)

Gerard Domagk (1930)

the first commercially available antibacterial was Prontosil, a precursor of sulfonamides and a red azo dye developed by this German chemist

Prontosil

first commercially available antibacterial was

Prontosil

Gerard Domagk (1930) the first commercially

available antibacterial was Prontosil, a precursor of

Howard Florey and Ernst Chain (1938)

Isolated and introduced penicillins in therapy

manner of isolation is through lyophilization or freeze drying

Pasteur and Joubert (1938)

Discovered that anthrax culture were killed by another living organism - antibiosis

Waksman (1942)

Gave the formal definition of antibiotics

1940-1962

The “Golden era of antibiotics”. Most of the antibiotic classes we use as medicines today were discovered and introduced to the market.

ANTIBIOTICS

Substance produced by microorganisms (naturally) which has the capacity to inhibit even destroy other microorganism

ANTIBIOTICS

● Synthetic product produced by living organism as structural analog of a naturally occurring antibiotic

● Effective in low concentration

ANTIBIOTICS

A product of metabolism

penicilloic acid

Beta lactam ring produces an inactive

penicilloic acid

(metabolite of penicillin responsible for allergic reaction)

Beta lactams

form allergenic haptens in vivo. Bacteria (staphylococcus produces beta lactamases)are capable of inactivating drugs by using certain enzymes

PENICILLINASES (INACTIVATION)

Beta lactams form allergenic haptens in vivo. Bacteria (staphylococcus produces beta lactamases) are capable of inactivating drugs by using certain enzymes

B-lactamases

Acylases

Beta lactams form allergenic haptens in vivo. Bacteria (staphylococcus produces beta lactamases) are capable of inactivating drugs by using certain enzymes:

Acylases

are also a variety enzymes that have been isolated from some bacteria, and these enzymes cleave the acylamino side chain of the antibiotic → inactive

B-lactamases

are a group of enzymes specifically designed to degrade and inactivate beta lactam antibiotics by directly attacking the beta lactam bond which leads to ring opening and inactivating the antibiotic.