33. Bacteria and Antibiotic Resistance

Professor Imperiali introduces the concept of antibiotic resistance through an interactive exercise with students. She asks them to suggest ways bacteria could evolve to become resistant to antibiotics, like degrading or pumping out the antibiotic, decreasing influx, mutating the target, or overproducing the target.

A student suggests enzymes could break down antibiotics. Imperiali agrees, giving the example of penicillin and beta-lactamases. Another student proposes decreasing influx. Imperiali notes that is difficult but gives the example of less permeable cell walls in Gram-negative bacteria.

Imperiali shows examples of viruses named after the organs they infect, like polio, hepatitis, and Epstein-Barr. She notes childhood vaccinations have nearly eradicated some viruses. She highlights how viruses like HPV and Epstein-Barr are linked to cancer. She also discusses viral statistics, like 35 million people infected with HIV in 2011.

Imperiali explains the difference between endemic, epidemic, and pandemic diseases. She notes how plane travel can quickly spread viruses globally. She gives examples like Ebola, avian flu, and the Spanish flu possibly originating from troop ships in WWI.

Imperiali notes how before good HIV antivirals, infected mothers transmitted the virus to babies. But with proper treatment of the mother and Caesarean delivery, transmission to newborns can now often be prevented, which is a huge advance.

Imperiali compares sizes of the smallest viruses like rhinovirus to a ribosome. She notes larger viruses like influenza and HIV, but emphasizes all are much smaller than bacteria or mitochondria.

Imperiali shows electron microscope images of viruses, noting they can be rod-shaped, icosahedral, enveloped, etc. She focuses on bacterial phages, saying they look like lunar landers and shoot their nucleic acids into host cells.

Imperiali explains how icosahedral viral capsids are assembled from repeating geometric triangle subunits coded for by just a few viral genes. She shows how these triangles tile to form the 20 faces of an icosahedron, a very efficient use of genetic material.

Imperiali walks through replication of a double-stranded DNA virus like smallpox. Viral DNA replicates using host proteins, transcribes mRNAs to make viral proteins like capsids, assembles new virions, and buds from the cell surface.

Imperiali explains how influenza enters with negative-sense RNA, which is converted by a viral polymerase to positive-sense mRNA to translate viral proteins. New virions assemble at the cell membrane and bud out.

Imperiali notes how influenza has a segmented genome, enabling reassortment into new strains when different viruses co-infect a cell. This causes antigenic shifts like bird+pig strains leading to more severe pandemics unprotected by vaccines.