Abstract
Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S. Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S. Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S. Typhi strains would be key for effective therapeutic management and cancer prevention.
Highlights
Salmonella enterica subspecies enterica serovar Typhi is a rod shaped, flagellated, aerobic, Gram-negative bacterium
The results showed an enhanced colonization of the gallbladder as compared to infected mice lacking gallstones [33]
Typhi appears to be favoured by biofilm formation, which is most effective on the surface of the gallstone
Summary
Salmonella enterica subspecies enterica serovar Typhi is a rod shaped, flagellated, aerobic, Gram-negative bacterium It is a human-specific pathogen that causes typhoid or enteric fever [1]. Typhi is endemic approximately 1–4% of infected individuals become chronic asymptomatic carriers representing a threat to local public health [9,10]. Typhi endemic regions, such as Chile, Bolivia, Ecuador, as well as some areas of India, Pakistan, Japan and Korea, have shown that approximately 90% of chronically infected carriers are gallstones carriers, and this association is, in turn, indicated as a major predisposing factor for the development of gallbladder cancer (GC) [15,16,17,18,19]. Typhi infection and gallstone disease represent the most important risk factors [22]. When stones exceed 3 cm the risk is tenfold higher compared with smaller stones [23,24]
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