Which organism would be least susceptible to penicillin due to the absence of a cell wall?

• A. Staphylococcus aureus
• B. Streptococcus epidermidis
• C. Mycoplasma pneumoniae
• D. Corynebacterium diphtheriae

Answer: (C)

Penicillin works by inhibiting the enzymes that build and cross-link peptidoglycan in the bacterial cell wall. If an organism lacks a cell wall, there is nothing for penicillin to target, so the drug is ineffective. Mycoplasma pneumoniae fits this scenario because it has no peptidoglycan and instead relies on a cholesterol-rich cell membrane for structure. That’s why it is inherently resistant to beta-lactam antibiotics like penicillin and is typically treated with non–beta-lactam agents such as macrolides or tetracyclines.

The other organisms listed possess cell walls with peptidoglycan, so penicillin can disrupt their wall synthesis under normal circumstances (though resistance can occur in some strains for other reasons, the absence of a cell wall is the defining reason penicillin wouldn’t work for the organism without one).