Non-typhoidal Salmonella DNA traces in gallbladder cancer

08 Mar 2016

Non-typhoidal Salmonella DNA traces in gallbladder cancer

Non-typhoidal Salmonella isolates – a hitherto unrecognized entity in gallbladder carcinogenesis

Dr Amit Dutt, Intermediate Fellow, ACTREC Mumbai

Gallbladder cancer is a relatively rare cancer in developed nations with an incidence as low as 1–2.5 per 100,000. However in South America and India gallbladder cancer remains a major problem with the disease presenting at an advanced stage and occurring at an incidence of 15.5 and 21.5 per 100,000, respectively. The rare occurrences of gallbladder cancer cases in the developed world have contributed to the generally poor understanding of the disease (Barreto et al, 2014). Recently Scanu et al. reported that Salmonella and its chronic infectious state affect the AKT/MAP kinase pathway and ubiquitin-like pathway in gallbladder cancer and provides the inflammatory stimulus that drives this type of cancer (Scanu et al, 2015)followed by a News & Views article entitled “The Deadly Bite of Salmonella Typhi”, underscoring the significance of association between Salmonella and gall bladder carcinoma (Zhang et al, 2015).

However, systematic evidence for association at the resolution of single base 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.

We present the first evidence to support the association of non-typhoidal Salmonella species along with typhoidal isolates in gallbladder cancer, which may play a role in analogous to Helicobacter pylori in gastric cancer and Fusobacterium in colon cancer, with implication in disease management and therapeutic approach. The focus of treatment in typhoid-endemic countries such as India has historically been solely on eliminating typhoidal Salmonella species often underestimating the contribution of the non-typhoidal isolates that show an inherent higher resistance to the standard antibiotics (Crump et al, 2015)resulting in their ability to lead to chronic carrier state in humans. The presence of non-typhoidal Salmonella species in our study highlights that in typhoid, as well as gallbladder cancer-endemic countries such as India and other similar countries, efforts must be directed not only at treating typhoid fever, but also diagnosing and appropriately managing non-typhoidal Salmonella species.

Barreto SG, Dutt A, Chaudhary A (2014) A genetic model for gallbladder carcinogenesis and its dissemination. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 25: 1086-1097

Chandrani P, Kulkarni V, Iyer P, Upadhyay P, Chaubal R, Das P, Mulherkar R, Singh R, Dutt A (2015) NGS-based approach to determine the presence of HPV and their sites of integration in human cancer genome. British journal of cancer 112: 1958-1965

Crump J, Sjölund-Karlsson M, Gordon M, Parry C (2015) Epidemiology, Clinical Presentation, Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella Infections. Clin Microbiol Rev

Scanu T, Spaapen RM, Bakker JM, Pratap CB, Wu LE, Hofland I, Broeks A, Shukla VK, Kumar M, Janssen H, Song JY, Neefjes-Borst EA, Te Riele H, Holden DW, Nath G, Neefjes J (2015) Salmonella Manipulation of Host Signaling Pathways Provokes Cellular Transformation Associated with Gallbladder Carcinoma. Cell Host Microbe 17: 763-774

Zhang K, Hornef M, Fulde M (2015) The deadly bite of Salmonella Typhi. EMBO reports 16: 887-888

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