Abstract
Salmonella enterica is a common foodborne, facultative intracellular enteropathogen. Human-restricted typhoidal S. enterica serovars Typhi (STY) or Paratyphi A (SPA) cause severe typhoid or paratyphoid fever, while many S. enterica serovar Typhimurium (STM) strains have a broad host range and in human hosts usually lead to a self-limiting gastroenteritis. Due to restriction of STY and SPA to primate hosts, experimental systems for studying the pathogenesis of typhoid and paratyphoid fever are limited. Therefore, STM infection of susceptible mice is commonly considered as model system for studying these diseases. The type III secretion system encoded by Salmonella pathogenicity island 2 (SPI2-T3SS) is a key factor for intracellular survival of Salmonella. Inside host cells, the pathogen resides within the Salmonella-containing vacuole (SCV) and induces tubular structures extending from the SCV, termed Salmonella-induced filaments (SIF). This study applies single cell analyses approaches, which are flow cytometry of Salmonella harboring dual fluorescent protein reporters, effector translocation, and correlative light and electron microscopy to investigate the fate and activities of intracellular STY and SPA. The SPI2-T3SS of STY and SPA is functional in translocation of effector proteins, SCV and SIF formation. However, only a low proportion of intracellular STY and SPA are actively deploying SPI2-T3SS and STY and SPA exhibited a rapid decline of protein biosynthesis upon experimental induction. A role of SPI2-T3SS for proliferation of STY and SPA in epithelial cells was observed, but not for survival or proliferation in phagocytic host cells. Our results indicate that reduced intracellular activities are factors of the stealth strategy of STY and SPA and facilitate systemic spread and persistence of the typhoidal Salmonella.
Highlights
Salmonella enterica is a versatile gastrointestinal pathogen with the ability to cause diseases ranging from acute, usually self-limiting gastroenteritis due to infections by non-typhoidal Salmonella (NTS) to severe systemic infections caused by typhoidal Salmonella (TS) serovars
To investigate the response of such as Typhi (STY) and serovar Paratyphi A (SPA) to the intracellular environment in various host cells, we analyzed if genes in SPI2 encoding the T3SS are expressed
Analyses were performed in WT and ΔssrB strains of serovar Typhimurium (STM), SPA or STY
Summary
Salmonella enterica is a versatile gastrointestinal pathogen with the ability to cause diseases ranging from acute, usually self-limiting gastroenteritis due to infections by non-typhoidal Salmonella (NTS) to severe systemic infections caused by typhoidal Salmonella (TS) serovars. Infections by S. enterica serovars such as Typhi (STY) and Paratyphi A (SPA) represent a continuing threat to human health. The global burden of disease by TS infections is continuously high with about 27,000,000 infected people and 200,000 deaths annually worldwide, and the increased frequency of multidrug-resistant strains of TS, as well as coinfections cause problems for treatment of typhoid fever [1,2]. While NTS infections are commonly associated with a strong inflammatory response leading to effective immune defense at the intestinal epithelium, TS infections lack this response and allow the pathogen to enter circulation and lymphatic system, and infect solid organs (reviewed in [3]). The ability to survive phagocytosis and to persist and proliferate in infected host cells is considered a key virulence trait of S. enterica [4]
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