M07.15.013 Intrinsic Drug Resistance

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Learning Objective

By the end of this section, the learner should be able to define intrinsic drug resistance, identify why certain bacteria are naturally resistant to specific antibiotics, and recognize classic Step-1–level examples of intrinsic resistance.

Intrinsic drug resistance refers to the natural, built-in inability of a bacterial species to be affected by a particular antibiotic. This resistance is not acquired via mutation or gene transfer; it is simply due to the organism’s innate structure, metabolism, or lack of a drug target.

Key features:

A bacterium is intrinsically resistant when it does not possess the molecular target of the drug.
Resistance also occurs when normal anatomy or physiology blocks the drug’s access or action.

Classic Examples

Bacteria lacking mycolic acids → intrinsically resistant to isoniazid (INH requires mycolic acid synthesis to exert its effect).
Mycoplasma species (no peptidoglycan cell wall) → intrinsically resistant to β-lactams, such as penicillin, because these drugs target cell wall synthesis.