How Antibiotics attack Bacteria

Antibiotics are designed to block some essential steps in the life cycleof the bacteria and prevent their growth and survival.

How Bacteria may develop resistance

Bacteria have great ability to adapt to hostile environments. They develop resistance to agents that threaten their survival. All these resistance mechanisms are generated through genetic modifications so that theprogeny will also be resistant to the drug. These genetic modifications occur at two levels: mutations in the chromosomal genes and horizontal transfer* of resistance genes from one bacterium to another.

Unlike human and animal cells, bacterial cells have a thick cell wall. Antibiotics of the class beta-lactams (which includes penicillin) bind and inactivate an enzyme (called ‘penicillin binding protein’- PBP), which is essential for the synthesis of the cell wall. A bacterial cell without a robust cell wall cannot survive.

There are many ways by which bacteria can defend themselves from hostile aspects of an environment. Forexample, bacteria can produce an enzyme that binds to the drug and makesit ineffective. Penicillin is deactivated through the production of beta-lactamase. Alternatively, the target itselfmay be altered so that the drug may no longer be able tobind to it. This can be seen in the other types of penicillin resistant bacteria where the structure of the binding site PBP is altered. If an essential metabolite is altered by the drug, the bacteria may stop needing that metabolite.

Folic acid is required by both bacteria and humans for the synthesis of nucleic acids andproteins. Unlike humans, bacteria cannot usepre-formed folic acid and synthesize their ownfolic acid. An important starting compound forthe synthesis of folic acid is para- aminobenzoic acid(PABA). Sulfonamidesand other sulfa drugs are analogous to PABA and bacteria cannot distinguish between the two. These compounds compete with PABA inbiochemical reactions. When chosen, they block the synthesis of folic acid and thus the formation of nucleic acids and proteins, killing the bacteria.

Resistance to sulfonamide arises when bacteria develop the ability to utilize the pre-existing folic acid rather than synthesizing it. And then some bacteria may reduce the permeability of the cell wall to the drug or increase the active efflux (pumping out) of the drug from across the cell wall so that it may not be available at a high enough concentration to be effective.

An essential step in DNA replication prior to cell division is the unwinding of the double stranded DNA molecule. This is carried out by an enzyme called DNA gyrase. A class of antibiotics known as Fluoroquinolones bind to bacterial DNA gyrase and inhibit DNA replication, preventing bacterial

In a series of complex genetic maneuvers, the cell will be able to repair the damage and resume DNA replication. However, this process known as the “SOS repair ” is error-prone; it can randomly substitute the wrong bases during DNA replication leading to gene mutations. Most of these random mutations are harmful to the bacteria. But some of them may be beneficial to

growth.Rifamycins inhibit RNA synthesis in an analogous manner.

the bacteria and provide an advantage to its survival by triggering a defense mechanism.

Ribosomes are structures on which protein synthesis takes place. Tetracycline, Er ythromycin and similar antibiotics bind to ribosomes to prevent protein synthesis