Pseudogenization of sopA and sopE2 is functionally linked and contributes to virulence of Salmonella enterica serovar Typhi.
The difference in host range between Salmonella enterica serovar Typhimurium (S. Typhimurium) and S. enterica serovar Typhi (S. Typhi) can be partially attributed to pseudogenes. Pseudogenes are genomic segments homologous to functional genes that do not encode functional products due to the presence of genetic defects. S. Typhi lacks several protein effectors implicated in invasion or other important processes necessary for full virulence of S. Typhimurium. SopA and SopE2, effectors that have been lost by pseudogenization in S. Typhi, correspond to an ubiquitin ligase involved in cytokine production by infected cells, and to a guanine exchange factor necessary for invasion of epithelial cells, respectively. We hypothesized that sopA and/or sopE pseudogenization contributed to the virulence of S. Typhi. In this work, we found that S. Typhi expressing S. Typhimurium sopE2 exhibited a decreased invasion in different epithelial cell lines compared with S. Typhi WT. S. Typhimurium sopA completely abolished the hypo-invasive phenotype observed in S. Typhi expressing S. Typhimurium sopE2, suggesting that functional SopA and SopE2 participate concertedly in the invasion process. Finally, the expression of S. Typhimurium sopA and/or sopE2 in S. Typhi, determined changes in the secretion of IL-8 and IL-18 in infected epithelial cells.
Laboratorio de Microbiología, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
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LM
Valenzuela
Laboratorio de Microbiología, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.
A A
AA
Hidalgo
Laboratorio de Microbiología, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
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L
Rodríguez
Laboratorio de Microbiología, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
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IM
Urrutia
Laboratorio de Microbiología, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
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AP
Ortega
Laboratorio de Microbiología, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.
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NA
Villagra
Gut Microbiota and Clostridia Research Group, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
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Paredes-Sabja
Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
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IL
Calderón
Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
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F
Gil
Laboratorio de Microbiología Molecular, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile.
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CP
Saavedra
Laboratorio de Microbiología, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.
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GC
Mora
Laboratorio de Microbiología, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile. Electronic address: jfuentes@unab.cl.
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JA
Fuentes
D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D015870:Gene Expression; D005838:Genotype; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D009154:Mutation; D011544:Pseudogenes; D012485:Salmonella typhi / Q000235:genetics* / Q000472:pathogenicity*; D014435:Typhoid Fever / Q000382:microbiology*; D014774:Virulence / Q000235:genetics*
D001426:Bacterial Proteins; D016207:Cytokines; D020662:Guanine Nucleotide Exchange Factors; C436324:SopE2 protein, Salmonella typhimurium; C060971:SopA protein, Bacteria
Host-specificity; Pseudogene; Reductive evolution; sopA; sopE2