Study on correlation of chronic salmonella enterica serovar typhi infection with gallbladder disease

Abstract

Salmonella enterica serovar Typhi (S. Typhi), the etiological agent of typhoid fever, is a human-restricted pathogen causing exhibiting both acute and chronic phases of infection. Most of the studies focus on understanding the initial phases leading to systemic infection, with very few reports for chronic lifestyle adapted by the organism. The gallbladder is shown to be a primary site for chronic infection by S. Typhi from where the organisms disseminate into the environment via shedding through faeces or urine, thus spreading typhoid fever. This phase of chronic infection is generally asymptomatic and strongly associated with gallstones formed in the gallbladder. Furthermore, chronic persistence is also considered as one of the predisposing factors for gallbladder cancer. Many researchers associate findings such as the confinement of S. Typhi to gallbladder, their ability to resist antibiotic therapy and the intermittent shedding of organisms, to biofilm-forming ability of the organisms within the gallbladder. Cholesterol-gallstones are shown to be the best substrates for biofilm formation by Salmonella spp., and the bacteria produce various biofilm-related proteins that function in a highly coordinated manner to form successful matrix-encased biofilms. In this study, we screen for S. Typhi persisting in the gallbladder from regions within the country which are mostly endemic for typhoid fever and reporting high incidences of gallbladder diseases. We further characterize these isolates in vitro based on their tolerance to bile, ability to form biofilms and resistance to antibiotics. These studies suggest that S. Typhi does persist in the gallbladder of patients, successfully adapting to bile and showing good ability to form biofilms on cholesterol-coated surfaces. As a part of our efforts to partly understand mechanisms underlying bacterial adaptation to bile, we examine the implications of quorum sensing and persister cells as a response to bile generated oxidative stress in S. Typhi gallbladder isolates.