title: Lose to win: marT pseudogenization in Salmonella enterica serovar Typhi contributed to the surV-dependent survival to H2O2, and inside human macrophage-like cells.
abstract: The difference in host range between Salmonella enterica serovar Typhimurium (S. Typhimurium) and Salmonella enterica serovar Typhi (S. Typhi) can be partially attributed to the gain of functions, to the loss of functions (i.e. pseudogenization), or to a combination of both processes. As previously reported, the loss of functions by pseudogenization may play a role in bacterial evolution, especially in host-restricted pathogens such as S. Typhi. The marT-fidL operon, located at the SPI-3, encodes the MarT transcriptional regulator and a hypothetical protein (i.e. FidL) with no significant similarities to known proteins, respectively. Even though predicted S. Typhimurium FidL exhibit 99.4% identity with S. Typhi FidL, marT has been annotated as a pseudogene in S. Typhi. In this work, we found that S. Typhi expressing S. Typhimurium marT-fidL exhibited an increased accumulation of reactive oxygen species (ROS), leading to a decreased survival in presence of H2O2. Moreover, we found that that the presence of a functional copy of S. Typhimurium marT-fidL in S. Typhi resulted in a repression of surV (STY4039), an ORF found in the S. Typhi SPI-3 but absent from S. Typhimurium SPI-3, that contribute to the resistance to H2O2by decreasing the accumulation of ROS. Finally, we observed that the presence of S. Typhimurium marT-fidL in S. Typhi negatively affected the survival inside macrophage-like cells, but not in epithelial cells, after 24h post infection. Therefore, this work provides evidence arguing that marT pseudogenization in Salmonella Typhi contributed to the surV-dependent survival against H2O2, and inside human macrophage-like cells. This is a good example of how the loss of functions (marT pseudogenization) and the gain of functions (presence of surV) might contribute to phenotypic changes improving virulence.
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile. Electronic address: all.ortega@uandresbello.edu.
authors: A P
authors: AP
authors: Ortega
authors: Laboratorio de Patogénesis Molecular y Antimicrobianos, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile. Electronic address: nicolas.villagra@unab.cl.
authors: N A
authors: NA
authors: Villagra
authors: Laboratorio de Microbiología, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile. Electronic address: iurrutia@ciq.uchile.cl.
authors: I M
authors: IM
authors: Urrutia
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile. Electronic address: lu.valenzuela.v@uandresbello.edu.
authors: L M
authors: LM
authors: Valenzuela
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile. Electronic address: a.talamilla@uandresbello.edu.
authors: A
authors: A
authors: Talamilla-Espinoza
authors: Laboratorio de Patogénesis Molecular y Antimicrobianos, Facultad de Medicina, Escuela de Farmacia, Universidad Andres Bello, Santiago, Chile. Electronic address: a.hidalgocea@uandresbello.edu.
authors: A A
authors: AA
authors: Hidalgo
authors: Center for Integrative Medicine and Innovative Science (CIMIS), Facultad de Medicina, Universidad Andres Bello, Santiago, Chile. Electronic address: paula.rodas@unab.cl.
authors: P I
authors: PI
authors: Rodas
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile. Electronic address: fernandogil@unab.cl.
authors: F
authors: F
authors: Gil
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile. Electronic address: lcalderon@unab.cl.
authors: I L
authors: IL
authors: Calderón
authors: Microbiota-Host Interactions and Clostridia Research Group, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile; Center for Bioinformatics and Integrative Biology, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile. Electronic address: daniel.paredes.sabja@gmail.com.
authors: D
authors: D
authors: Paredes-Sabja
authors: Laboratorio de Patogénesis Molecular y Antimicrobianos, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile. Electronic address: gmora@unab.cl.
authors: G C
authors: GC
authors: Mora
authors: Laboratorio de Genética y Patogénesis Bacteriana, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago, Chile. Electronic address: jfuentes@unab.cl.
authors: J A
authors: JA
authors: Fuentes
mesh_terms: D003001:Cloning, Molecular; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D009876:Operon / Q000235:genetics; D011544:Pseudogenes / Q000235:genetics*; D012485:Salmonella typhi / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D020298:U937 Cells
chemical_list: D006861:Hydrogen Peroxide
keywords: H(2)O(2) resistance; Macrophage survival; Pseudogene; Salmonella; marT; surV