Andreas J. Bäumler

Animal models of Salmonella infections: enteritis versus typhoid fever

The most common disease syndromes caused by Salmonella serotypes in humans, typhoid fever and enteritis, can be modeled using Salmonella enterica serotype Typhimurium infections in mice and calves, respectively. This article reviews murine typhoid and bovine enteritis and discusses strengths, limitations and distinctive features of these animal models.

Non-typhoidal salmonellosis: emerging problems

Two major changes in the epidemiology of non-typhoidal salmonellosis have occurred during the second half of the 20th century. First, Salmonella typhimurium strains resistant to multiple antibiotics have emerged and spread within populations of food animals. Secondly, Salmonella enteritidis has emerged as a major egg-associated pathogen. This article reviews available data on the origins of the human epidemics.

Salmonella typhimurium leucine‐rich repeat proteins are targeted to the SPI1 and SPI2 type III secretion systems

Salmonellae encode two virulence‐associated type III secretion systems (TTSS) within Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2). Two Salmonella typhimurium genes, sspH1 and sspH2, that encode proteins similar to the Shigella flexneri and Yersinia species TTSS substrates, IpaH and YopM, were identified. SspH1 and SspH2 are proteins containing leucine‐rich repeats that are differentially targeted to the SPI1 and SPI2 TTSS. sspH2 transcription was induced within RAW264.7 macrophages, and was dependent upon the SPI2‐encoded regulator ssrA/ssrB. In contrast, sspH1 transcription is independent of SPI2, and is not induced after bacterial phagocytosis by eukaryotic cells. Infection of eukaryotic cells with strains expressing a SspH2–CyaA fusion protein resulted in SPI2 TTSS‐dependent cAMP increases. In contrast, SspH1–CyaA‐mediated cAMP increases were both SPI1 and SPI2 TTSS dependent. sspH2‐like sequences were found in most Salmonella serotypes examined, whereas sspH1 was detected in only one S. typhimurium isolate, indicating that the copy number of sspH genes can be variable within Salmonella serotypes. S. typhimurium deleted for both sspH1 and sspH2 was not able to cause a lethal infection in calves, indicating that these genes participate in S. typhimurium virulence for animals.

Molecular Pathogenesis of Salmonella enterica Serotype Typhimurium-Induced Diarrhea

Recent studies on the molecular pathogenesis of Salmonella enterica serotype Typhimurium-induced enterocolitis using tissue culture models and the neonatal calf model have led to an improved understanding of key events occurring during the complex series of host-pathogen interactions leading to

The Salmonella enterica Serotype Typhimurium Effector Proteins SipA, SopA, SopB, SopD, and SopE2 Act in Concert To Induce Diarrhea in Calves

ABSTRACT Salmonella enterica serotype Typhimurium requires a functional type III secretion system encoded by Salmonella pathogenicity island 1 (SPI1) to cause diarrhea. We investigated the role of genes encoding secreted target proteins of the SPI1-associated type III secretion system for enteropathogenicity in calves. Salmonella serotype Typhimurium strains having mutations in sptP, avrA, sspH1, or slrP induced fluid secretion in the bovine ligated ileal loop model at levels similar to that of the wild type. In contrast, mutations in sipA, sopA, sopB, sopD, or sopE2 significantly reduced fluid accumulation in bovine ligated ileal loops at 8 h postinfection. A strain carrying mutations in sipA, sopA, sopB, sopD, and sopE2 (sipA sopABDE2 mutant) caused the same level of fluid accumulation in bovine ligated ileal loops as a strain carrying a mutation in sipB, a SPI1 gene required for the translocation of effector proteins into host cells. A positive correlation was observed between the severity of histopathological lesions detected in the ileal mucosa and the levels of fluid accumulation induced by the different mutants. After oral infection of calves, the Salmonella serotype Typhimurium sipAsopABDE2 mutant caused only mild diarrhea and was more strongly attenuated than strains having only single mutations. These data demonstrate that SipA, SopA, SopB, SopD, and SopE2 are major virulence factors responsible for diarrhea during Salmonella serotype Typhimurium infection of calves.

SipA, SopA, SopB, SopD, and SopE2 Contribute to Salmonella enterica Serotype Typhimurium Invasion of Epithelial Cells

ABSTRACT The centisome 63 type III secretion system (T3SS-1) encoded by Salmonella pathogenicity island 1 (SPI1) mediates invasion of epithelial cells by Salmonella enterica serotype Typhimurium. Characterization of mutants lacking individual genes has revealed that T3SS-1 secreted proteins (effectors) SopE2 and SopB are required for invasion while the SipA protein accelerates entry into cells. Here we have revisited the question of which T3SS-1 effectors contribute to the invasion of epithelial cells by complementing a strain lacking all of the effector genes that are required to cause diarrhea in a calf (a sipA sopABDE2 mutant). Introduction of either the cloned sipA, the cloned sopB, or the cloned sopE2 gene increased the invasiveness of the sipA sopABDE2 mutant for nonpolarized HT-29 cells. However, a contribution of sopA or sopD to invasion was not apparent when invasion assays were performed with the nonpolarized colon carcinoma cell lines T84 and HT-29. In contrast, introduction of either the sopA, the sopB, the sopD, or the sopE2 gene increased the invasiveness of the sipA sopABDE2 mutant for polarized T84 cells. Furthermore, introduction of a plasmid carrying sipA and sopB increased the invasiveness of the sipA sopABDE2 mutant for polarized T84 cells significantly compared to the introduction of plasmids carrying only sipA or sopB. We conclude that SipA, SopA, SopB, SopD, and SopE2 contribute to S. enterica serotype Typhimurium invasion of epithelial cells in vitro.

Salmonella enterica Serotype Typhimurium and Its Host-Adapted Variants

Salmonella enterica serotypes form a group of pathogens that differ widely in their host range within mammals and birds (Table [1][1]). Members of S. enterica seem to lie along a spectrum in terms of host range. At one end of this spectrum, S. enterica serotype Typhi is perhaps the most highly host-

Host adaptation and the emergence of infectious disease: the Salmonella paradigm

The recent emergence of food‐borne pathogens, such as Salmonella enterica serotype Enteritidis (S. enteritidis) and Escherichia coli O157:H7, has generated increasing interest in how infectious diseases can invade, persist and spread within new host populations. To alter their host range pathogens require adaptations, which ensure their circulation in a new animal population. Adaptations for circulation in different populations of vertebrate hosts seem to have been acquired multiple times within the genus Salmonella because extant Salmonella serotypes differ greatly with regard to host range. In this article, mechanisms involved in host adaptation are deduced by considering the influence of the host immune response on circulation of Salmonella serotypes within populations of vertebrate animals. This approach contributes to the identification of genes involved in host adaptation and provides new insights into the emergence of food‐borne pathogens.

Identification of a new iron regulated locus of Salmonella typhi

In order to identify genes belonging to the Fur regulon of Salmonella typhi which are absent from Escherichia coli K-12, a plasmid gene bank consisting of 4000 independent clones was screened for Fur regulated promoters using the Fur titration assay (FURTA). DNA probes generated from FURTA positive plasmids were then used for hybridization with chromosomal DNA from S. typhi, Salmonella typhimurium and E. coli. Using these techniques we identified an iron regulated locus present in S. typhi and S. typhimurium but not in E. coli. Further cloning and nucleotide sequence analysis identified two open reading frames, termed iroBC, organized in a typical operon structure. The genes iroBC were located at 4 and 57 centisomes on the physical maps of Salmonella typhi and S. typhimurium, respectively. This region of the S. typhimurium chromosome contains a large DNA loop which is absent from the corresponding area of the E. coli chromosome. Finally, we developed a new method for generation of single copy transcriptional fusions. A suicide vector was constructed, which allows for the generation of chromosomal fusions to the promoterless E. coli lacZYA genes. By integration of this construct at the iro locus we could establish iron responsive expression of iroBC.

Salmonella enterica Serovar Typhi Possesses a Unique Repertoire of Fimbrial Gene Sequences

ABSTRACT Salmonella enterica serotype Typhi differs from nontyphoidal Salmonella serotypes by its strict host adaptation to humans and higher primates. Since fimbriae have been implicated in host adaptation, we investigated whether the serotype Typhi genome contains fimbrial operons which are unique to this pathogen or restricted to typhoidal Salmonella serotypes. This study established for the first time the total number of fimbrial operons present in an individual Salmonella serotype. The serotype Typhi CT18 genome, which has been sequenced by the Typhi Sequencing Group at the Sanger Centre, contained a type IV fimbrial operon, an orthologue of the agf operon, and 12 putative fimbrial operons of the chaperone-usher assembly class. In addition tosef, fim, saf, and tcf, which had been described previously in serotype Typhi, we identified eight new putative chaperone-usher-dependent fimbrial operons, which were termedbcf, sta, stb, ste, std, stc, stg, and sth. Hybridization analysis performed with 16 strains ofSalmonella reference collection C and 22 strains ofSalmonella reference collection B showed that all eight putative fimbrial operons of serotype Typhi were also present in a number of nontyphoidal Salmonella serotypes. Thus, a simple correlation between host range and the presence of a single fimbrial operon seems at present unlikely. However, the serotype Typhi genome differed from that of all other Salmonella serotypes investigated in that it contained a unique combination of putative fimbrial operons.