Penicillins are often more effective against Gram-positive bacteria than Gram- negative bacteria because of differences in their cell wall structures. Gram- positive bacteria have a thick peptidoglycan layer on the outside of their cell wall, which penicillins can easily access and inhibit, leading to weakening of the cell wall and bacterial death. In contrast, Gram-negative bacteria have an additional outer membrane that acts as a barrier, blocking many penicillin molecules from reaching the peptidoglycan layer, which is located between this outer membrane and the inner cell membrane. This outer membrane contains lipid components that limit the entry of penicillin, allowing Gram-negative bacteria to be relatively more resistant or less susceptible. Additionally, penicillin enters Gram-negative bacteria only through specific protein channels called porins, which restrict the rate and amount of antibiotic penetration based on the drug's size. Furthermore, Gram- negative bacteria may produce enzymes that degrade penicillin, adding to their resistance. Therefore, the structural differences and permeability barriers explain why penicillins are usually more effective against Gram-positive bacteria.