Association of non-typhoidal Salmonella with human gall bladder cancer
Clinical collaborator: Dr. Shailesh Shrikhande (TMH), Dr. George Barreto (Medanta)

Scanu et al. published a study describing association of Salmonella infection with gallbladder cancer that can lead to changes in the host signalling pathways (AKT/MAPK and ISG15/USP18 ubiquitin- like pathway) (Scanu et al, 2015). This study was further emphasized as a News & Views article entitled “The Deadly Bite of Salmonella Typhi” by Zhang et al. underscoring the significance of association between Salmonella and gall bladder carcinoma, (Zhang et al, 2015). We earlier, proposed a gallbladder carcinogenesis and dissemination model, wherein we discussed in depth dysplasia as a premalignant lesion that could potentially develop into carcinoma in situ and invasive gallbladder adenocarcinoma (Barreto et al, 2014). However, the ‘inflammatory stimulus’ to drive the initial cascade in the model remained unclear.

While the role of Salmonella infection in gallbladder cancer is better understood, systematic evidence for direct association of Salmonella in primary gallbladder cancer tissue has not been reported. We have examined whole exome sequence of 26 primary gall bladder tumour and paired normal samples for presence of 143 HPV types along with 6 common Salmonella serotypes using a computational subtraction pipeline based on the HPVDetetctor, we recently described (Chandrani et al, 2015). Based on our evaluation: association of typhoidal Salmonella species were found in 11 of 26 gallbladder cancer samples, non-typhoidal Salmonella species in 12 of 26 gallbladder cancer, and 6 samples were found co-infected with both.

Here, we present the first evidence to support the association of non-typhoidal Salmonella species along with typhoidal isolates in gallbladder cancer, which has its implication in disease management and therapeutic approach. Furthermore, owing to the ability of Salmonella infection to stimulate a host response, it is likely that these bacteria are able to provide the continued ‘inflammatory stimulus’ and play a role in gallbladder cancer analogous to Helicobacter pylori in gastric cancer and Fusobacterium in colon cancer.

Barreto et al. Annals of oncology (2014) 25: 1086-1097
Chandrani et al. British journal of cancer (2015) 112: 1958-1965
Scanu et al. Cell Host Microbe (2015)17: 763-774
Zhang et al. EMBO reports (2015)16: 887-888