Biochemical mechanism of resistance:

It may vary and involve alteration in drug penetration, binding sites, metabolic pathway and/or drug inactivating enzymes.

a. Alteration in drug penetration:

• Decreased penetrability of AMA into bacterial cell may occur either due to change in permeability of cell wall or altered transport system.
• Resistance in gram -ve bacteria may occur due to decreased porin sizes or numbers which normally allow intracellular accumulation of hydrophilic antimicrobial like aminoglycosides
• Some resistant bacteria causes rapid efflux of antimicrobial drug via energy dependent carrier processes. In this case reduce concentration of antimicrobial agent in bacteria fails to produce action because it is unable to gain access to site of action.

b. Alteration in binding sites:

• Molecular alterations in target sites in an organism can confer resistance because in such condition, antimicrobials fail to bind to their specific sites and thus cannot perform their actions.
• For ex: alteration in 30S ribosomal subunit impart resistance to aminoglycosides and altered structure of 50S ribosomal subunit imparts resistance to erythromycin.

c. Alteration in metabolic pathway:

• This may impart resistance by passing the reactions inhibited by antimicrobial agent.
• For ex; some sulphonamide resistant bacteria donot require intracellular para-aminobenzoic acid (PABA) but can utilise preformed folic acid unlike mammalian cells.

d. Drug inactivating enzymes:

• Increased production of drug inactivating enzymes by certain microbes also confers resistance.
• These enzymes are either inducible or constitutive.
• Ex; β-lactamase destroy penicillin and cephalosporin by cleaving β-lactam rings. Chloramphenicol is inactivated by acetyl transferases.