Abstract
Bacterial genotoxins are effectors that cause DNA damage in target cells. Many aspects of the biology of these toxins have been characterised in vitro, such as structure, cellular internalisation pathways and effects on the target cells. However, little is known about their function in vivo. Salmonella enterica serovar Typhi (S. Typhi) is a Gram-negative, intracellular bacterium that causes typhoid fever, a debilitating disease infecting more than 20 million people every year. S. Typhiproduce a genotoxin named typhoid toxin (TT), but its role in the contest of host infection is poorly characterized. The major obstacle in addressing this issue is that S. Typhi is exclusively a human pathogen. To overcome this limitation, we have used as model bacterium S. Typhimurium, and engineered it to produce endogenous levels of an active and inactive typhoid toxin, hereby named as TT (or genotoxic) and cdtB (or control), respectively. To our surprise, infection with the genotoxin strain strongly suppressed intestinal inflammation, leading to a better survival of the host during the acute phase of infection, suggesting typhoid toxin may exert a protective role. The presence of a functional genotoxin was also associated with an increased frequency of asymptomatic carriers.
Highlights
Bacterial genotoxins are proteins and metabolic products secreted by pathogenic and commensal bacteria
From cytolethal distending toxin (CDT), which is mainly produced by extracellular bacteria, the typhoid toxin is produced upon bacterial internalisation and replication within the Salmonella containing vacuole (SCV), inside the host cell
In S. typhimurium, the toxin is secreted by the producing bacterium within Outer Membrane Vesicles (OMVs), which accumulate within the SCV and are released into the extracellular milieu via an exocytosis-like process
Summary
Bacterial genotoxins are proteins and metabolic products secreted by pathogenic and commensal bacteria. MICROREVIEW on: Del Bel Belluz L, Guidi R, Pateras IS, Levi L, Mihaljevic B, Rouf SF, Wrande M, Candela M, Turroni S, Nastasi C, Consolandi C, Peano C, Tebaldi T, Viero G, Gorgoulis VG, Krejsgaard T, Rhen M, Frisan T (2016).
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have