Abstract
In Salmonella enterica serovar Typhimurium, oxidoreductases of the thioredoxin superfamily contribute to bacterial invasiveness, intracellular replication and to the virulence in BALB/c mice as well as in the soil nematode Caenorhabditis elegans. The scsABCD gene cluster, present in many but not all enteric bacteria, codes for four putative oxidoreductases of the thioredoxin superfamily. Here we have analyzed the potential role of the scs genes in oxidative stress tolerance and virulence in S. Typhimurium. An scsABCD deletion mutant showed moderate sensitization to the redox-active transition metal ion copper and increased protein carbonylation upon exposure to hydrogen peroxide. Still, the scsABCD mutant was not significantly affected for invasiveness or intracellular replication in respectively cultured epithelial or macrophage-like cells. However, we noted a significant copper chloride sensitivity of SPI1 T3SS mediated invasiveness that strongly depended on the presence of the scs genes. The scsABCD deletion mutant was not attenuated in animal infection models. In contrast, the mutant showed a moderate increase in its competitive index upon intraperitoneal challenge and enhanced invasiveness in small intestinal ileal loops of BALB/c mice. Moreover, deletion of the scsABCD genes restored the invasiveness of a trxA mutant in epithelial cells and its virulence in C. elegans. Our findings thus demonstrate that the scs gene cluster conditionally affects virulence and underscore the complex interactions between oxidoreductases of the thioredoxin superfamily in maintaining host adaptation of S. Typhimurium.
Highlights
The scs genes are contained in two transcriptional units read from the same DNA strand [24]; one consistsing of scsA followed by a second including the scsBCD genes
E. coli K-12 and many other members of Enterobacteriacae and related organisms lack scs gene sequences, or contain only selected scs genes positioned between cbpA and agp genes (Fig.1A)
Reactive oxygen species play an important role in the pathogenesis of many bacterial species both in cell culture setting and for virulence in man, mice and nematodes [12,13,14,15,16,17]
Summary
Typhimurium) is a facultative intracellular enteric pathogen that traditionally has been used as a model organism for studying typhoid fever caused by the human adapted serovar Typhi [1,2]. Invasion is followed by dissemination and intracellular bacterial replication in phagocytic cells of the liver and spleen. Typhimurium in mammalian cell culture and in mice, as well as in alternative host infection models, strongly relies on horizontally acquired DNA regions termed as Salmonella pathogenicity islands (SPI:s) [3]. Two of the SPI:s, SPI1 and SPI2, code for protein type III secretion systems (T3SS) that translocate bacterial effector proteins into host cells. SPI1 and SPI2 enable the bacteria to transcytose the intestinal epithelial barrier, and disseminate to replicate in macrophages of the liver and spleen respectively [7,8]. SPI1 and SPI2 T3SS modulate pro-inflammatory responses of the host during Salmonella infection [9,10,11]
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