Penicillins

Penicillins:

Penicillins are the first antibiotics to be used clinically as antibiotics. Penicillins were first obtained from Penicillium Notatum, and present source is through Penicillium Chrysogenum.

Chemistry:

Penicillins have two rings perfused together namely one is the 𝛃-lactum ring and the other one is the thiazolidine ring, an side chain is attached through the 𝛃-lactam ring through an amide linkage.

The first used Penicillin was Penicillin G, structurally it is having a benzyl side chain attached to the 𝛃-lactam ring through the amide linkage 

Mechanism of action:

The main target for 𝛃-lactam antibiotics is to inhibit the cell wall synthesis in bacteria by interfering in the process of synthesis.

The bacteria basically adopts the following scheme in the synthesis of Bacterial cell wall

UDP-N-acetylmuramic acid pentapeptide(also called Park nucleotide) + UDP-N-acetyl glucosamine

↓

These Peptidoglycan residue is are linked up and the UDP is split off

                                                               ↓ transpeptidase enzyme ← (-) 𝛃-lactam

Then the D-alanine group is cleaved off by the help of enzyme "transpeptidases" and the energy obtained is used to establish cross linkage between the peptidoglycans, thus providing rigidity and stability to the cell wall

Note: As the cross linkage is inhibited by the antibiotics the cell wall the bacteria swells due to its hyperosmotics cytoplasm (due to hyperosmotics nature the extracellular fluid is imbibed in the cell) and the cell becomes likely to burst due to the increased internal pressure, resulting in the bacterial lysis.

Also there is a difference cell wall structure of the gram (+) and the gram (-) bacteria. The gram (+) Bactria's cell wall are mainly consisting of peptidoglycan part but the gram (-) Bactria's cell wall consist of alternating layer of both lipoprotein and peptidoglycan hence the gram (+) bacteria are more susceptible to the 𝛃-lactam antibiotics.

Benzyl Penicillin:

The natural penicillin (Penicillin G), is also known as Benzyl Penicillin, the PnG (Penicillin G) is narrow spectrum antibiotics i.e. limited primarly to only gram (+) bacteria and few others like 

1. cocci: Streptococci, pneumococci, staph. aureus were initially synsitive to PnG but now have developed resistance, some gram (-) cocci are also synsitive to PnG
2. Baccilli: B.anthracis, Corynebacterium diphtheriae and majority of Clostridia and listeria, but the gram (-) baccilli are resistant

Bacterial Resistance:

The basic fundamental behind the resistance developed by the bacteria's is the 

• Development of thick lipoprotien layer, i.e. the Penicillins binding Protiens (PBPs) remains deeper inside the layers of lipoproteins hence PnG is unable to approach the PBPs.
• Another important mechansim is development of Penicillinase enzyme, which cleave the beta lactam bond in the beta lactam ring of penicillins

Some bacteria become Penicillins tolerant rather than the Penicillins destroying for example., Mithicillin resistant staph. aureus (MRSA) by altering in the Penicillin binding Proteins (PBPs) i.e. reduced affinity for Penicillins, another mechansim is that the gram (-) bacteria have porins channels through which the penicillins usually enters in the cells, the bacteria develops resistance by altering or closing the porin channels