Emerging insights into the biology of typhoid toxin

•Typhoid toxin is a unique A2B5 exotoxin and a key S. Typhi virulence factor.•Its biological program differs from related toxins in many important ways.•It is highly adapted to the intracellular niche S. Typhi adopts during infection.•It binds Neu5Ac-terminated sialoglycans to enable its uptake into human cells.•It appears to be a distinguishing factor in S. Typhi pathogenesis.