Biofilm Producing Salmonella Typhi: Chronic Colonization and Development of Gallbladder Cancer

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.

Microbial biofilm correlates with an increased antibiotic tolerance and poor therapeutic outcome in infective endocarditis

“…The specific cause of most failures of antibiotic therapy is still unclear. Growing evidence suggests that the ability to produce biofilms may play a major pathogenetic role in supporting microbial adhesion and persistence while protecting from antimicrobial drugs [22,73,74]. Our results support the notion that IE represents an example of a biofilm-related infection, which, in turn, is associated with an increased antibiotic tolerance.…”

Modulatory Effect of Lippia alba Essential Oil on the Activity of Clinically Used Antimicrobial Agents on Salmonella typhi and Shigella dysenteriae Biofilm

“…and Shigella spp. have the biofilm-forming capacity to be important virulence factor [36,37]. Biofilms are bacterial agglomerations attached to a surface, and embedded in an extracellular matrix, which provides protection against both antimicrobial substances and host defense mechanisms.…”

Typhus abdominalis und Paratyphus

“…Dauerausscheider mit Persistenz von Salmonella Typhi z. B. im Biofilm auf Gallensteinen, sind selten und machen weniger als 5 % der Fälle aus [1,[24][25][26][27]. Es gilt als gesichert, dass Salmonella Typhi ein Typhus-Toxin mit kanzerogenem Potenzial produziert, das in dafür empfänglichen humanen Zellen DNA-Schäden und Zellzyklusveränderungen hervorruft [25].…”

“…B. im Biofilm auf Gallensteinen, sind selten und machen weniger als 5 % der Fälle aus [1,[24][25][26][27]. Es gilt als gesichert, dass Salmonella Typhi ein Typhus-Toxin mit kanzerogenem Potenzial produziert, das in dafür empfänglichen humanen Zellen DNA-Schäden und Zellzyklusveränderungen hervorruft [25]. Darüber hinaus kann die Biofilmproduktion von Salmonella Typhi ein Schlüsselfaktor für die Förderung einer persistierenden Infektion der Gallenblase sein, wodurch eine chronische lokale Entzündungsreaktion aufrechterhalten und das Epithel wiederholt durch krebserregende Toxine geschädigt wird [25,26].…”