Abstract

Typhoid fever is a major global health problem and is the result of systemic infections caused by the human-adapted bacterial pathogen Salmonella enterica serovar Typhi (S. Typhi). The pathology underlying S. Typhi infections significantly differ from infections caused by broad host range serovars of the same species, which are a common cause of gastroenteritis. Accordingly, identifying S. Typhi genetic factors that impart functionality absent from broad host range serovars offers insights into its unique biology. Here, we used an in-silico approach to explore the function of an uncharacterized 14-gene S. Typhi genomic islet. Our results indicated that this islet was specific to the S. enterica species, where it was encoded by the Typhi and Paratyphi A serovars, but was generally absent from non-typhoidal serovars. Evidence was gathered using comparative genomics and sequence analysis tools, and indicated that this islet was comprised of Type VI secretion system (T6SS) and contact-dependent growth inhibition (CDI) genes, the majority of which appeared to encode orphan immunity proteins that protected against the activities of effectors and toxins absent from the S. Typhi genome. We herein propose that this islet represents an immune system that protects S. Typhi against competing bacteria within the human gut.

Highlights

  • Typhoid fever is a major health problem in the developing world and is a life-threatening disease that results from systemic infections by the bacterial pathogen Salmonella enterica serovarTyphi

  • Evidence was gathered using comparative genomics and sequence analysis tools, and indicated that this islet was comprised of Type VI secretion system (T6SS) and contact-dependent growth inhibition (CDI) genes, the majority of which appeared to encode orphan immunity proteins that protected against the activities of effectors and toxins absent from the S

  • A significant proportion of these genes are associated with putative prophage and ~150 such genes are confined to Salmonella Pathogenicity Island 7 (SPI-7), an established S

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Summary

Introduction

Typhoid fever is a major health problem in the developing world and is a life-threatening disease that results from systemic infections by the bacterial pathogen Salmonella enterica serovarTyphi Typhoid fever is a major health problem in the developing world and is a life-threatening disease that results from systemic infections by the bacterial pathogen Salmonella enterica serovar. Salmonella infections are first established in the intestinal tract, typically following consumption of contaminated food or water. Typhi’s subsequent systemic spread via the lymphatic system and bloodstream, triggering the onset of typhoid fever, a disease characterized by a high and prolonged fever and a range of variable symptoms and complications, some of which are life-threatening [1,2]. Typhi and are thought to be critical for disease transmission [3,4,5]. S. Typhi is a human-restricted pathogen and its virulence and disease properties are similar to other human-restricted S. enterica serovars, most notably Paratyphi A [6,7,8].

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