1887

Abstract

is a recognised cause of foodborne intoxication and antibiotic-associated diarrhoea (AAD), which are both mediated by staphylococcal enterotoxins. However, unlike foodborne intoxication, AAD appears to require infection of the host. While intoxication is widely studied, little is known about pathogenesis in the context of gastrointestinal infection.

To develop a mouse model of gastrointestinal infection.

An established AAD mouse model was adapted for infection, and damage observed via histopathological analysis and immunostaining of intestinal tissues.

Various strains colonised the mouse model, and analysis showed that although clinical signs of disease were not seen, infection induced damage in the small intestine, disrupting host structures essential for epithelial integrity. Studies using a staphylococcal enterotoxin B mutant showed that this toxin may contribute to damage during gastrointestinal infection.

This work presents a new mouse model of gastrointestinal infection, while also providing insight into the pathogenesis of in the gut.

Funding
This study was supported by the:
  • Australian Government Research Training Program Scholarship (Award PhD Scholarship)
    • Principle Award Recipient: Sarah Larcombe
  • Australian Research Council (Award FT120100779)
    • Principle Award Recipient: Dena Lyras
  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001163
2020-01-31
2024-05-06
Loading full text...

Full text loading...

/deliver/fulltext/jmm/69/2/290.html?itemId=/content/journal/jmm/10.1099/jmm.0.001163&mimeType=html&fmt=ahah

References

  1. Argudín MA, Mendoza MC, Rodicio MR. Food poisoning and Staphylococcus aureus enterotoxins. Toxins 2010; 2:1751–1773 [View Article]
    [Google Scholar]
  2. Lane AB, Copeland NK, Onmus-Leone F, Lawler JV. Methicillin-Resistant Staphylococcus aureus as a probable cause of antibiotic-associated enterocolitis. Case Rep Infect Dis 2018; 2018:3106305–3 [View Article]
    [Google Scholar]
  3. Bergevin M, Marion A, Farber D, Golding GR, Lévesque S. Severe MRSA enterocolitis caused by a strain harboring enterotoxins D, G, and I. Emerg Infect Dis 2017; 23:865–867 [View Article]
    [Google Scholar]
  4. Wei Y, Gong J, Zhu W, Guo D, Gu L et al. Fecal microbiota transplantation restores dysbiosis in patients with methicillin resistant Staphylococcus aureus enterocolitis. BMC Infect Dis 2015; 15:265 [View Article]
    [Google Scholar]
  5. Avery LM, Zempel M, Weiss E. Case of antibiotic-associated diarrhea caused by Staphylococcus aureus enterocolitis. Am J Health Syst Pharm 2015; 72:943–951 [View Article]
    [Google Scholar]
  6. Gravet A, Rondeau M, Harf-Monteil C, Grunenberger F, Monteil H et al. Predominant Staphylococcus aureus isolated from antibiotic-associated diarrhea is clinically relevant and produces enterotoxin A and the bicomponent toxin LukE-LukD. J Clin Microbiol 1999; 37:4012–4019 [View Article]
    [Google Scholar]
  7. Lo TS, Borchardt SM. Antibiotic-associated diarrhea due to methicillin-resistant Staphylococcus aureus . Diagn Microbiol Infect Dis 2009; 63:388–389 [View Article]
    [Google Scholar]
  8. Larcombe S, Hutton ML, Lyras D. Involvement of bacteria other than Clostridium difficile in antibiotic-associated diarrhoea. Trends Microbiol 2016; 24:463–476 [View Article]
    [Google Scholar]
  9. Boyce JM, Havill NL. Nosocomial antibiotic-associated diarrhea associated with enterotoxin-producing strains of methicillin-resistant Staphylococcus aureus . Am J Gastroenterol 2005; 100:1828–1834 [View Article]
    [Google Scholar]
  10. Fremont DH, Hendrickson WA, Marrack P, Kappler J. Structures of an MHC class II molecule with covalently bound single peptides. Science 1996; 272:1001–1004 [View Article]
    [Google Scholar]
  11. Yeung RS, Penninger JM, Kündig T, Khoo W, Ohashi PS et al. Human CD4 and human major histocompatibility complex class II (DQ6) transgenic mice: supersensitivity to superantigen-induced septic shock. Eur J Immunol 1996; 26:1074–1082 [View Article]
    [Google Scholar]
  12. Lu J, Wang A, Ansari S, Hershberg RM, McKay DM. Colonic bacterial superantigens evoke an inflammatory response and exaggerate disease in mice recovering from colitis. Gastroenterology 2003; 125:1785–1795 [View Article]
    [Google Scholar]
  13. Pérez-Bosque A, Moretó M. A rat model of mild intestinal inflammation induced by Staphylococcus aureus enterotoxin B. Proc Nutr Soc 2010; 69:447–453 [View Article]
    [Google Scholar]
  14. Misawa Y, Kelley KA, Wang X, Wang L, Park WB et al. Staphylococcus aureus colonization of the mouse gastrointestinal tract Is modulated by wall teichoic acid, capsule, and surface proteins. PLoS Pathog 2015; 11:e1005061 [View Article]
    [Google Scholar]
  15. Gries DM, Pultz NJ, Donskey CJ. Growth in cecal mucus facilitates colonization of the mouse intestinal tract by methicillin-resistant Staphylococcus aureus . J Infect Dis 2005; 192:1621–1627 [View Article]
    [Google Scholar]
  16. Holtfreter S, Radcliff FJ, Grumann D, Read H, Johnson S et al. Characterization of a mouse-adapted Staphylococcus aureus strain. PLoS One 2013; 8:e71142 [View Article]
    [Google Scholar]
  17. Flaxman A, van Diemen PM, Yamaguchi Y, Allen E, Lindemann C et al. Development of persistent gastrointestinal S. aureus carriage in mice. Sci Rep 2017; 7:12415 [View Article]
    [Google Scholar]
  18. Uramatsu M, Matsumoto T, Tateda K, Shibuya K, Miyazaki S et al. Involvement of endotoxin in the mortality of mice with gut-derived sepsis due to methicillin-resistant Staphylococcus aureus . Microbiol Immunol 2010; 54:330–337 [View Article]
    [Google Scholar]
  19. Lyon SA, Hutton ML, Rood JI, Cheung JK, Lyras D. CdtR regulates TcdA and TcdB production in Clostridium difficile . PLoS Pathog 2016; 12:e1005758 [View Article]
    [Google Scholar]
  20. Larcombe S, Hutton ML, Riley TV, Abud HE, Lyras D. Diverse bacterial species contribute to antibiotic-associated diarrhoea and gastrointestinal damage. J Infect 2018; 77:417–426 [View Article]
    [Google Scholar]
  21. Yao J, Zhong J, Fang Y, Geisinger E, Novick RP et al. Use of targetrons to disrupt essential and nonessential genes in Staphylococcus aureus reveals temperature sensitivity of Ll.LtrB group II intron splicing. RNA 2006; 12:1271–1281 [View Article]
    [Google Scholar]
  22. Pérez-Bosque A, Amat C, Polo J, Campbell JM, Crenshaw J et al. Spray-dried animal plasma prevents the effects of Staphylococcus aureus enterotoxin B on intestinal barrier function in weaned rats. J Nutr 2006; 136:2838–2843 [View Article]
    [Google Scholar]
  23. Bateman BT, Donegan NP, Jarry TM, Palma M, Cheung AL. Evaluation of a tetracycline-inducible promoter in Staphylococcus aureus in vitro and in vivo and its application in demonstrating the role of sigB in microcolony formation. Infect Immun 2001; 69:7851–7857 [View Article]
    [Google Scholar]
  24. Kreiswirth BN, Löfdahl S, Betley MJ, O'Reilly M, Schlievert PM et al. The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage. Nature 1983; 305:709–712 [View Article]
    [Google Scholar]
  25. Monk IR, Shah IM, Xu M, Tan MW, Foster TJ. Transforming the untransformable: application of direct transformation to manipulate genetically Staphylococcus aureus and Staphylococcus epidermidis . mBio 2012; 3:e00277–11 [View Article]
    [Google Scholar]
  26. Moolenbeek C, Ruitenberg EJ. The "Swiss roll": a simple technique for histological studies of the rodent intestine. Lab Anim 1981; 15:57–60 [View Article]
    [Google Scholar]
  27. Larsen MV, Cosentino S, Rasmussen S, Friis C, Hasman H et al. Multilocus sequence typing of total-genome-sequenced bacteria. J Clin Microbiol 2012; 50:1355–1361 [View Article]
    [Google Scholar]
  28. Bartels MD, Petersen A, Worning P, Nielsen JB, Larner-Svensson H et al. Comparing whole-genome sequencing with Sanger sequencing for spa typing of methicillin-resistant Staphylococcus aureus . J Clin Microbiol 2014; 52:4305–4308 [View Article]
    [Google Scholar]
  29. Hutton ML, Cunningham BA, MacKin KE, Lyon SA, James ML et al. Bovine antibodies targeting primary and recurrent Clostridium difficile disease are a potent antibiotic alternative. Sci Rep 2017; 7:3665 [View Article]
    [Google Scholar]
  30. Carter GP, Chakravorty A, Pham Nguyen TA, Mileto S, Schreiber F et al. Defining the roles of TcdA and TcdB in localized gastrointestinal disease, systemic organ damage, and the host response during Clostridium difficile infections. mBio 2015; 6:e00551 [View Article]
    [Google Scholar]
  31. Squire MM, Carter GP, Mackin KE, Chakravorty A, Norén T et al. Novel molecular type of Clostridium difficile in neonatal pigs, Western Australia. Emerg Infect Dis 2013; 19:790–792 [View Article]
    [Google Scholar]
  32. Li M, Diep BA, Villaruz AE, Braughton KR, Jiang X et al. Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus . Proc Natl Acad Sci USA 2009; 106:5883–5888 [View Article]
    [Google Scholar]
  33. Sieradzki K, Leski T, Dick J, Borio L, Tomasz A. Evolution of a vancomycin-intermediate Staphylococcus aureus strain in vivo: multiple changes in the antibiotic resistance phenotypes of a single lineage of methicillin-resistant S. aureus under the impact of antibiotics administered for chemotherapy. J Clin Microbiol 2003; 41:1687–1693 [View Article]
    [Google Scholar]
  34. Endt K, Stecher B, Chaffron S, Slack E, Tchitchek N et al. The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea. PLoS Pathog 2010; 6:e1001097 [View Article]
    [Google Scholar]
  35. Kamada N, Seo SU, Chen GY, Núñez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol 2013; 13:321–335 [View Article]
    [Google Scholar]
  36. Kernbauer E, Maurer K, Torres VJ, Shopsin B, Cadwell K. Gastrointestinal dissemination and transmission of Staphylococcus aureus following bacteremia. Infect Immun 2015; 83:372–378 [View Article]
    [Google Scholar]
  37. Ashida H, Ogawa M, Kim M, Mimuro H, Sasakawa C. Bacteria and host interactions in the gut epithelial barrier. Nat Chem Biol 2011; 8:36–45 [View Article]
    [Google Scholar]
  38. Pinchuk IV, Beswick EJ, Reyes VE. Staphylococcal enterotoxins. Toxins 2010; 2:2177–2197 [View Article]
    [Google Scholar]
  39. Shupp JW, Jett M, Pontzer CH. Identification of a transcytosis epitope on staphylococcal enterotoxins. Infect Immun 2002; 70:2178–2186 [View Article]
    [Google Scholar]
  40. Casaletto JB, Saotome I, Curto M, McClatchey AI. Ezrin-mediated apical integrity is required for intestinal homeostasis. Proc Natl Acad Sci USA 2011; 108:11924–11929 [View Article]
    [Google Scholar]
  41. Hutton ML, MacKin KE, Chakravorty A, Lyras D. Small animal models for the study of Clostridium difficile disease pathogenesis. FEMS Microbiol Lett 2014; 352:140–149 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001163
Loading
/content/journal/jmm/10.1099/jmm.0.001163
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error