CDS (II) 2020 General Knowledge · Question 110 of 120

Correct — A, cell wall formation in bacteria. A bacterial cell wall is a mesh of peptidoglycan whose strands must be cross-linked to hold pressure, and the cross-linking is done by enzymes known as penicillin-binding proteins. Penicillin's four-membered beta-lactam ring mimics the natural target these enzymes act on, so they bind the drug instead and the final cross-linking step never happens. A growing bacterium then builds wall that cannot bear load; water flows in down the osmotic gradient and the cell bursts. That mechanism explains the drug's most valuable property, which is selective toxicity: human cells have no cell wall and no peptidoglycan, so there is nothing in us for penicillin to attack, and it can be given in large doses with little harm. It also explains a limitation — penicillin kills growing bacteria, not dormant ones, and it does nothing at all to viruses, which have no cell wall either.

• (b)RNA synthesis in bacteria — Blocking bacterial RNA synthesis is the mechanism of rifampicin, which binds the bacterial RNA polymerase. Penicillin has no effect on transcription.
• (c)DNA synthesis in bacteria — Interfering with bacterial DNA replication is what the quinolone antibiotics such as ciprofloxacin do, by inhibiting DNA gyrase and topoisomerase. Penicillin does not reach the nucleoid at all.
• (d)division in bacteria — The most tempting wrong answer because division does stop, but that is a consequence rather than the target. Penicillin blocks one step in wall construction; the failure of division and the bursting of the cell follow from it.

Antibiotics work by attacking structures or processes that bacteria have and human cells do not, and they are grouped by that target. Beta-lactams — the penicillins and cephalosporins — hit cell wall synthesis. Tetracyclines, aminoglycosides and macrolides hit the bacterial ribosome, which differs from ours. Quinolones hit DNA replication, rifampicin hits RNA synthesis and sulphonamides hit folate synthesis. Penicillin was discovered by Alexander Fleming in 1928 from a contaminating Penicillium mould and was developed into a usable drug by Florey and Chain in the early 1940s.

The reasoning shortcut for the whole antibiotic topic is to ask what a bacterium has that we do not — a peptidoglycan wall and a different ribosome — because that is where the drugs act. Applied here it points straight to the wall. The distinction between option (a) and option (d) is the one that separates a candidate who has learnt the mechanism from one who has learnt the outcome, and examiners exploit it. Two consequences are worth carrying because they turn up as separate questions: antibiotics do not work against viral illnesses such as the common cold, influenza or COVID-19, since viruses have no cell wall, ribosome or metabolism of their own to attack; and bacteria acquire resistance to penicillin largely by producing beta-lactamase enzymes that cut the ring open before it can act.

• Penicillin inhibits the cross-linking of peptidoglycan, the final step in building the bacterial cell wall.
• It works by binding penicillin-binding proteins through its beta-lactam ring, so the enzymes that should cross-link the wall are taken out of action.
• Human cells have no cell wall and no peptidoglycan, which is the basis of penicillin's selective toxicity.
• Penicillin was discovered by Alexander Fleming in 1928 and turned into a therapeutic drug by Howard Florey and Ernst Chain in the early 1940s; the three shared the 1945 Nobel Prize in Physiology or Medicine.
• Resistance arises chiefly through bacterial beta-lactamase enzymes that break the beta-lactam ring.

• Choosing 'division' because division does stop; the drug's target is the wall, and the halt in division is the effect.
• Taking antibiotics for a viral illness such as a cold or influenza.
• Assuming a broader-spectrum antibiotic must work by a different mechanism; many are beta-lactams with the same wall target.

As a mechanism item, as a discovery-and-scientist item on Fleming, or inside a statement set on antimicrobial resistance.

• practice — not a real PYQ

  Antibiotics are ineffective against viral infections chiefly because viruses

  • (a)are too small to be reached by the drug
  • (b)lack the cell wall, ribosomes and metabolic pathways that antibiotics target
  • (c)multiply too rapidly
  • (d)are destroyed by the immune system anyway

  Answer(b) lack the cell wall, ribosomes and metabolic pathways that antibiotics target — a virus uses the host cell's machinery, so there is nothing bacterial for the drug to attack.

• practice — not a real PYQ

  The main structural component of the bacterial cell wall is

  • (a)cellulose
  • (b)chitin
  • (c)peptidoglycan
  • (d)suberin

  Answer(c) peptidoglycan — cellulose builds plant walls, chitin fungal walls and arthropod exoskeletons, and suberin waterproofs cork.