The human bile salt sodium deoxycholate induces metabolic and cell envelope changes in Typhi leading to bile resistance No Access

Abstract

serovar Typhi (. Typhi) is the etiological agent of typhoid fever. To establish an infection in the human host, this pathogen must survive the presence of bile salts in the gut and gallbladder.

. Typhi uses multiple genetic elements to resist the presence of human bile.

To determine the genetic elements that . Typhi utilizes to tolerate the human bile salt sodium deoxycholate.

A collection of . Typhi mutant strains was evaluated for their ability to growth in the presence of sodium deoxycholate and ox-bile. Additionally, transcriptomic and proteomic responses elicited by sodium deoxycholate on . Typhi cultures were also analysed.

Multiple transcriptional factors and some of their dependent genes involved in central metabolism, as well as in cell envelope, are required for deoxycholate resistance.

These findings suggest that metabolic adaptation to bile is focused on enhancing energy production to sustain synthesis of cell envelope components exposed to damage by bile salts.

Funding
This study was supported by the:
  • Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (Award IN203621)
    • Principle Award Recipient: IsmaelHernández-Lucas
  • Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México (Award IN203618)
    • Principle Award Recipient: IsmaelHernández-Lucas
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001461
2022-01-10
2024-03-28
Loading full text...

Full text loading...

References

  1. Šarenac TM, Mikov M. Bile acid synthesis: from nature to the chemical modification and synthesis and their applications as drugs and nutrients. Front Pharmacol 2018; 9:939. [View Article] [PubMed]
    [Google Scholar]
  2. Begley M, Gahan CGM, Hill C. The interaction between bacteria and bile. FEMS Microbiol Rev 2005; 29:625–651 [View Article] [PubMed]
    [Google Scholar]
  3. Hofmann AF, Hagey LR. Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci 2008; 65:2461–2483 [View Article] [PubMed]
    [Google Scholar]
  4. Urdaneta V, Casadesús J. Interactions between bacteria and bile salts in the gastrointestinal and hepatobiliary tracts. Front Med 2017; 4:163 [View Article]
    [Google Scholar]
  5. Coleman R, Lowe PJ, Billington D. Membrane lipid composition and susceptibility to bile salt damage. Biochim Biophys Acta 1980; 599:294–300 [View Article] [PubMed]
    [Google Scholar]
  6. Fujisawa T, Mori M. Influence of bile salts on beta-glucuronidase activity of intestinal bacteria. Lett Appl Microbiol 1996; 22:271–274 [View Article] [PubMed]
    [Google Scholar]
  7. Gómez Zavaglia A, Kociubinski G, Pérez P, Disalvo E, De Antoni G. Effect of bile on the lipid composition and surface properties of bifidobacteria. J Appl Microbiol 2002; 93:794–799 [View Article] [PubMed]
    [Google Scholar]
  8. Prieto AI, Ramos-Morales F, Casadesús J. Bile-induced DNA damage in Salmonella enterica. Genetics 2004; 168:1787–1794 [View Article] [PubMed]
    [Google Scholar]
  9. Sanyal AJ, Hirsch JI, Moore EW. Premicellar taurocholate enhances calcium uptake from all regions of rat small intestine. Gastroenterology 1994; 106:866–874 [View Article] [PubMed]
    [Google Scholar]
  10. Symeonidis A, Marangos M. Iron and microbial growth. Insight and Control of Infectious Disease in Global Scenario 2012289–330
    [Google Scholar]
  11. Hernández SB, Cota I, Ducret A, Aussel L, Casadesús J. Adaptation and preadaptation of Salmonella enterica to Bile. PLoS Genet 2012; 8:e1002459 [View Article] [PubMed]
    [Google Scholar]
  12. Datsenko KA, Wanner BL. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 2000; 97:6640–6645 [View Article] [PubMed]
    [Google Scholar]
  13. Medina-Aparicio L, Rodriguez-Gutierrez S, Rebollar-Flores JE, Martínez-Batallar ÁG, Mendoza-Mejía BD et al. The CRISPR-Cas system is involved in OmpR genetic regulation for outer membrane protein synthesis in Salmonella Typhi. Front Microbiol 2021; 12:657404. [View Article] [PubMed]
    [Google Scholar]
  14. Villarreal JM, Becerra-Lobato N, Rebollar-Flores JE, Medina-Aparicio L, Carbajal-Gómez E et al. The Salmonella enterica serovar Typhi ltrR-ompR-ompC-ompF genes are involved in resistance to the bile salt sodium deoxycholate and in bacterial transformation. Mol Microbiol 2014; 92:1005–1024 [View Article] [PubMed]
    [Google Scholar]
  15. Gallego-Hernández AL, Hernández-Lucas I, De la Cruz MA, Olvera L, Morett E et al. Transcriptional regulation of the assT-dsbL-dsbI gene cluster in Salmonella enterica serovar Typhi IMSS-1 depends on LeuO, H-NS, and specific growth conditions. J Bacteriol 2012; 194:2254–2264 [View Article] [PubMed]
    [Google Scholar]
  16. Kawano M, Oshima T, Kasai H, Mori H. Molecular characterization of long direct repeat (LDR) sequences expressing a stable mRNA encoding for a 35-amino-acid cell-killing peptide and a cis-encoded small antisense RNA in Escherichia coli. Mol Microbiol 2002; 45:333–349 [View Article] [PubMed]
    [Google Scholar]
  17. Peña A, Sánchez NS, Álvarez H, Calahorra M, Ramírez J. Effects of high medium pH on growth, metabolism and transport in Saccharomyces cerevisiae. FEMS Yeast Res 2015; 15:fou005. [View Article] [PubMed]
    [Google Scholar]
  18. Rodríguez-Cruz M, Coral-Vázquez RM, Hernández-Stengele G, Sánchez R, Salazar E et al. Identification of putative ortholog gene blocks involved in gestant and lactating mammary gland development: a rodent cross-species microarray transcriptomics approach. Int J Genomics 2013; 2013:624681. [View Article] [PubMed]
    [Google Scholar]
  19. Hurkman WJ, Tanaka CK. Solubilization of plant membrane proteins for analysis by two-dimensional gel electrophoresis. Plant Physiol 1986; 81:802–806 [View Article] [PubMed]
    [Google Scholar]
  20. Encarnación S, Hernández M, Martínez-Batallar G, Contreras S, Vargas M del C et al. Comparative proteomics using 2-D gel electrophoresis and mass spectrometry as tools to dissect stimulons and regulons in bacteria with sequenced or partially sequenced genomes. Biol Proced Online 2005; 7:117–135 [View Article] [PubMed]
    [Google Scholar]
  21. Encarnación S, Guzmán Y, Dunn MF, Hernández M, del Carmen Vargas M et al. Proteome analysis of aerobic and fermentative metabolism in Rhizobium etli CE3. Proteomics 2003; 3:1077–1085 [View Article] [PubMed]
    [Google Scholar]
  22. Santos-Zavaleta A, Salgado H, Gama-Castro S, Sánchez-Pérez M, Gómez-Romero L et al. RegulonDB v 10.5: tackling challenges to unify classic and high throughput knowledge of gene regulation in E. coli K-12. Nucleic Acids Res 2019; 47:D212–D220 [View Article] [PubMed]
    [Google Scholar]
  23. Prieto AI, Hernández SB, Cota I, Pucciarelli MG, Orlov Y et al. Roles of the outer membrane protein AsmA of Salmonella enterica in the control of marRAB expression and invasion of epithelial cells. J Bacteriol 2009; 191:3615–3622 [View Article] [PubMed]
    [Google Scholar]
  24. Langridge GC, Phan M-D, Turner DJ, Perkins TT, Parts L et al. Simultaneous assay of every Salmonella Typhi gene using one million transposon mutants. Genome Res 2009; 19:2308–2316 [View Article] [PubMed]
    [Google Scholar]
  25. van Velkinburgh JC, Gunn JS. PhoP-PhoQ-regulated loci are required for enhanced bile resistance in Salmonella spp. Infect Immun 1999; 67:1614–1622 [View Article] [PubMed]
    [Google Scholar]
  26. Zheng D, Constantinidou C, Hobman JL, Minchin SD. Identification of the CRP regulon using in vitro and in vivo transcriptional profiling. Nucleic Acids Res 2004; 32:5874–5893 [View Article] [PubMed]
    [Google Scholar]
  27. Tsai M-J, Wang J-R, Yang C-D, Kao K-C, Huang W-L et al. PredCRP: predicting and analysing the regulatory roles of CRP from its binding sites in Escherichia coli. Sci Rep 2018; 8:951. [View Article] [PubMed]
    [Google Scholar]
  28. Soberón-Chávez G, Alcaraz LD, Morales E, Ponce-Soto GY, Servín-González L. The transcriptional regulators of the CRP family regulate different essential bacterial functions and can be inherited vertically and horizontally. Front Microbiol 2017; 8:959. [View Article] [PubMed]
    [Google Scholar]
  29. Unden G, Schirawski J. The oxygen-responsive transcriptional regulator FNR of Escherichia coli: the search for signals and reactions. Mol Microbiol 1997; 25:205–210 [View Article] [PubMed]
    [Google Scholar]
  30. Constantinidou C, Hobman JL, Griffiths L, Patel MD, Penn CW et al. A reassessment of the FNR regulon and transcriptomic analysis of the effects of nitrate, nitrite, NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to anaerobic growth. J Biol Chem 2006; 281:4802–4815 [View Article] [PubMed]
    [Google Scholar]
  31. Gunn JS. Mechanisms of bacterial resistance and response to bile. Microbes Infect 2000; 2:907–913 [View Article] [PubMed]
    [Google Scholar]
  32. Hernández SB, Ayala JA, Rico-Pérez G, García-del Portillo F, Casadesús J. Increased bile resistance in Salmonella enterica mutants lacking Prc periplasmic protease. Int Microbiol 2013; 16:87–92 [View Article] [PubMed]
    [Google Scholar]
  33. Yethon JA, Vinogradov E, Perry MB, Whitfield C. Mutation of the lipopolysaccharide core glycosyltransferase encoded by waaG destabilizes the outer membrane of Escherichia coli by interfering with core phosphorylation. J Bacteriol 2000; 182:5620–5623 [View Article] [PubMed]
    [Google Scholar]
  34. Møller AK, Leatham MP, Conway T, Nuijten PJM, de Haan LAM et al. An Escherichia coli MG1655 lipopolysaccharide deep-rough core mutant grows and survives in mouse cecal mucus but fails to colonize the mouse large intestine. Infect Immun 2003; 71:2142–2152 [View Article] [PubMed]
    [Google Scholar]
  35. Heinrichs DE, Yethon JA, Whitfield C. Molecular basis for structural diversity in the core regions of the lipopolysaccharides of Escherichia coli and Salmonella enterica. Mol Microbiol 1998; 30:221–232 [View Article] [PubMed]
    [Google Scholar]
  36. Ramos-Morales F, Prieto AI, Beuzón CR, Holden DW, Casadesús J. Role for Salmonella enterica enterobacterial common antigen in bile resistance and virulence. J Bacteriol 2003; 185:5328–5332 [View Article] [PubMed]
    [Google Scholar]
  37. Mahalakshmi S, Sunayana MR, SaiSree L, Reddy M. yciM is an essential gene required for regulation of lipopolysaccharide synthesis in Escherichia coli. Mol Microbiol 2014; 91:145–157 [View Article] [PubMed]
    [Google Scholar]
  38. Castelli ME, Véscovi EG. The Rcs signal transduction pathway is triggered by enterobacterial common antigen structure alterations in Serratia marcescens. J Bacteriol 2011; 193:63–74 [View Article] [PubMed]
    [Google Scholar]
  39. Prouty AM, Brodsky IE, Falkow S, Gunn JS. Bile-salt-mediated induction of antimicrobial and bile resistance in Salmonella typhimurium. Microbiology (Reading) 2004; 150:775–783 [View Article] [PubMed]
    [Google Scholar]
  40. Spöring I, Felgner S, Preuße M, Eckweiler D, Rohde M et al. Regulation of flagellum biosynthesis in response to cell envelope stress in Salmonella enterica Serovar Typhimurium. mBio 2018; 9:e00736-17. [View Article] [PubMed]
    [Google Scholar]
  41. Puente JL, Flores V, Fernández M, Fuchs Y, Calva E. Isolation of an ompC-like outer membrane protein gene from Salmonella typhi. Gene 1987; 61:75–83 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001461
Loading
/content/journal/jmm/10.1099/jmm.0.001461
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL

Supplementary material 2

EXCEL

Most cited Most Cited RSS feed