Learning Objective
By the end of this section, you should be able to explain how chromosomal mutations lead to antibiotic resistance and recognize key clinical examples (e.g., MRSA, S. pneumoniae).
Chromosome-Mediated Resistance
Chromosome-mediated resistance occurs when mutations in the bacterial chromosome alter how a drug interacts with the organism. These mutations typically arise spontaneously and are selected for during antibiotic exposure.
Key Features
Mutation of the drug target is the most common mechanism. The antibiotic can no longer bind effectively. Usually produces low-level resistance, but this may still be clinically important depending on the infection site.
Classic example:
MRSA acquires a mutated penicillin-binding protein (PBP2a), resulting in β-lactam resistance. Even subtle target modifications—such as in Streptococcus pneumoniae meningitis—can reduce antibiotic efficacy because drug levels in the CNS are lower.
