Penicillin is an antibiotic that disrupts cell wall formation. Natural penicillins are considered narrow-spectrum drugs. Based on your knowledge of bacterial cell structure, which of the following chemical modifications to penicillin could make it broader spectrum?

• A. Addition of an amino group to make the molecule more polar, allowing it to pass through porins in the Gram-negative plasma membranes more easily.
• B. Addition of a bulky side chain, to help protect it against antibiotic resistance mechanisms such as beta-lactamase.
• C. Addition of a benzene ring, to increase stability in acidic environments.
• D. Addition of a methyl group, to allow the drug to better mix with the hydrophobic cell wall.

Answer: (A)

Verified step by step guidance

1. Understand that natural penicillins are narrow-spectrum primarily because they are effective mostly against Gram-positive bacteria, which have thick peptidoglycan layers but lack an outer membrane.
2. Recall that Gram-negative bacteria have an outer membrane with porin channels that restrict the entry of many antibiotics, including natural penicillins, limiting their spectrum of activity.
3. Recognize that increasing the polarity of the penicillin molecule, such as by adding an amino group, can enhance its ability to pass through these porin channels in Gram-negative bacteria, thereby broadening its spectrum.
4. Consider that other modifications, like adding bulky side chains, benzene rings, or methyl groups, may affect stability or resistance but do not necessarily improve penetration through the outer membrane of Gram-negative bacteria.
5. Conclude that the key to broadening penicillin's spectrum lies in chemical modifications that improve its access to the target site inside Gram-negative bacteria, specifically by increasing polarity to facilitate passage through porins.