Antibiotics

INTRODUCTION

Low molecular weight antimicrobial agent produced by microorganism as secondary metabolites that kill or inhibit the growth of other microorganisms (pathogens) are called ANTIBIOTICS. Antibiotics are isolated from special microorganisms or other living organisms. Antibiotics are not effective against viruses. it is used to treat bacterial as well as some protozoan infections.



HISTORY

It is believed that antibiotic was first used by Chinese, about 2500 years ago. That time they used to apply soybean curd (moldy curd) for therapeutic use.

During ancient times Molds was used by Indians and Greeks for treatment of various infections.

Russian used to apply soil on the wounds.

In 1877 (France) Louis Pasture discovered the antibiotic against Anthrax disease. Through his discovery, he said that bacteria can kill other bacteria (Anthrax bacilli).

1928, Sir Alexander Flaming isolated the enzyme Lysozyme and antibiotic substance Penicillin from Penicillium notatum (fungi).

Streptomycin another antibiotic was discovered by A.Schatz and S.Waksman in 1940. This drug was effective against Mycobacterium tuberculosis and Gram-negative bacteria.

After Streptomycin various antibiotic were produced such as Tetracyclin. But these drugs were not effective against fungal infections. later since 1945 antibiotic was produced which can treat fungal infections. Example: Rifampicin (trade name Rifactin, Rifadin).


MODE OF ACTION 

Antibiotics affect the growth of microbial population by any of five major ways

• Cell wall synthesis inhibition:  

           1. Penicillin:                 Inhibits transpeptidation enzymes involved in cross-linking

           2. Vancomycin:            Binds directly to D-Ala-terminus and stops transpeptidation

• Protein synthesis inhibition :

          ANTIBIOTIC                                     TARGET

            Neomycin                                        16S ribosome

            Streptomycin                                   30S ribosome

            Tetracyclin                                      A site of ribosome

            Erythromycin                                  23S ribosome

          

• Nucleic acid synthesis inhibition:    - 

1. By blocking Replication 

                                                                      ANTIBIOTIC                         TARGET    

                                                                     Ciprofloxacin                   Inhibit bacterial DNA gyrase

                                                                     Novobiocin                      gyrA subunits of  gyrase 

                                                                     Mitomycin                       gyrB subunits of gyrase

           2. By blocking RNA synthesis. 

                                                                    

                       ANTIBIOTIC                  TARGET     

             

                                                    Streptolydigin                Beta subunit of RNA polymerase 

                                                          Rifampin                     Beta subunits of RNA polymerase

• Cell membrane disruption : 

        1. Sulfonamides       inhibit folic acid synthesis by competition with p-aminobenzoate                                                        

        2. Dapsone               Interferes with folic acid synthesis.

                

COMMONLY USED ANTIBIOTICS

1.  Penicillin: Firstly discovered by Alaxender Flaming. It was a metabolic by-product of the fungi Penicillium notatum. The mechanism of action of Penicillin is still unknown. It has been proposed that penicillin inhibits the transpeptidation reaction catalyzing enzyme which blocks the synthesis of cross- linked peptidoglycan and results osmotic lysis.

2. Tetracyclines: Tetracyclin is a four-ring structure and variety of side chains are attached to it. Tetracyclines are broad-spectrum antibodies. They are effective against gram-positive and gram-negative bacteria, rickettsias, mycoplasmas etc.

3. Chloramphenicol: First it was produced from Streptomyces venezuelze. Now it is produced by chemical processes. 

4. Erythromycin: Produced from strains of Streptomyces erythraeus. It consists of 12-23 carbon lactose ring which inhibits protein synthesis in Gram-positive bacteria.  

BY 

(PRAGATI PRIYA)