Bacterial Toxins from Staphylococcus aureus and Bordetella bronchiseptica Predispose the Horse’s Respiratory Tract to Equine Herpesvirus Type 1 Infection.
Abstract: Respiratory disease in horses is caused by a multifactorial complex of infectious agents and environmental factors. An important pathogen in horses is equine herpesvirus type 1 (EHV-1). During co-evolution with this ancient alphaherpesvirus, the horse's respiratory tract has developed multiple antiviral barriers. However, these barriers can become compromised by environmental threats. Pollens and mycotoxins enhance mucosal susceptibility to EHV-1 by interrupting cell junctions, allowing the virus to reach its basolateral receptor. Whether bacterial toxins also play a role in this impairment has not been studied yet. Here, we evaluated the role of α-hemolysin (Hla) and adenylate cyclase (ACT), toxins derived from the facultative pathogenic bacterium Staphylococcus aureus (S. aureus) and the primary pathogen Bordetella bronchiseptica (B. bronchiseptica), respectively. Equine respiratory mucosal explants were cultured at an air-liquid interface and pretreated with these toxins, prior to EHV-1 inoculation. Morphological analysis of hematoxylin-eosin (HE)-stained sections of the explants revealed a decreased epithelial thickness upon treatment with both toxins. Additionally, the Hla toxin induced detachment of epithelial cells and a partial loss of cilia. These morphological changes were correlated with increased EHV-1 replication in the epithelium, as assessed by immunofluorescent stainings and confocal microscopy. In view of these results, we argue that the ACT and Hla toxins increase the susceptibility of the epithelium to EHV-1 by disrupting the epithelial barrier function. In conclusion, this study is the first to report that bacterial exotoxins increase the horse's sensitivity to EHV-1 infection. Therefore, we propose that horses suffering from infection by S. aureus or B. bronchiseptica may be more susceptible to EHV-1 infection.
Publication Date: 2022-01-14 PubMed ID: 35062352PubMed Central: PMC8778808DOI: 10.3390/v14010149Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article reveals how toxins from bacteria Staphylococcus aureus and Bordetella bronchiseptica can make a horse’s respiratory tract more vulnerable to equine herpesvirus type 1 (EHV-1) infection.
Research Context and Aim
- The article begins by noting that respiratory illnesses in horses are caused by a combination of environmental and infectious factors.
- A significant pathogen in horses is EHV-1, with horses developing several antiviral barriers in their respiratory tract over time to minimize its impact.
- However, these barriers can be weakened by environmental elements such as pollens and mycotoxins, which increases vulnerability to EHV-1.
- The study sought to explore whether bacterial toxins also increase susceptibility to EHV-1.
Methodology and Investigated Toxins
- In an attempt to investigate this, the study inspected the effects of α-hemolysin (Hla) and adenylate cyclase (ACT), which are toxins from the bacteria Staphylococcus aureus and Bordetella bronchiseptica.
- The researchers carried out an experiment where equine respiratory mucosal explants were cultured and pretreated with these toxins, before inoculating EHV-1.
Observations and Findings
- The investigators found changes in the morphology of the tissues, such as reduced epithelial thickness, more pronounced after treatment with the toxins.
- The Hla toxin specifically resulted in the detachment of epithelial cells and partial loss of cilia.
- EHV-1 was also found to replicate more in the epithelium after the toxins had disturbed the epithelial barrier function.
Conclusions and Implication of the Findings
- Based on these findings, the study suggests that bacterial toxins ACT and Hla increase the susceptibility of a horse’s respiratory epithelium to EHV-1 infection.
- This is the first research that reports the enhancing effect of bacterial toxins on sensitivity to EHV-1 infection in horses.
- The study concludes by proposing that horses infected with Staphylococcus aureus or Bordetella bronchiseptica could be more prone to EHV-1 infection.
Cite This Article
APA
Van Crombrugge E, Vanbeylen E, Van Cleemput J, Van den Broeck W, Laval K, Nauwynck H.
(2022).
Bacterial Toxins from Staphylococcus aureus and Bordetella bronchiseptica Predispose the Horse’s Respiratory Tract to Equine Herpesvirus Type 1 Infection.
Viruses, 14(1).
https://doi.org/10.3390/v14010149 Publication
Researcher Affiliations
- Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
- Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
- Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
- Department of Morphology, Medical Imaging, Orthopedics and Nutrition, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
- Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
- Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.
MeSH Terms
- Animals
- Bacterial Toxins / pharmacology
- Bordetella bronchiseptica / metabolism
- Epithelial Cells / virology
- Hemolysin Proteins
- Herpesviridae Infections / drug therapy
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid / drug effects
- Horse Diseases / virology
- Horses
- Respiratory Mucosa / drug effects
- Respiratory Mucosa / virology
- Respiratory Tract Diseases / virology
- Staphylococcus aureus / metabolism
- Virus Replication / drug effects
Conflict of Interest Statement
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
References
This article includes 37 references
- Ainsworth D.M., Hackett R.P.. Disorders of the respiratory system.. Equine Intern. Med. 2004;2:289–353.
- Van Cleemput J., Poelaert K., Laval K., Impens F., Van den Broeck W., Gevaert K., Nauwynck H.J.. Pollens destroy respiratory epithelial cell junctions and drive alphaherpesvirus infection.. Sci. Rep. 2019;9:4787.
- Van Cleemput J., Poelaert K., Laval K., Van den Broeck W., Nauwynck H.J.. Deoxynivalenol, but not fumonisin B1, afla-toxin B1 or diesel exhaust particles disrupt integrity of the horse’s respiratory epithelium and predispose it for equine her-pesvirus type 1 infection.. Vet. Microbiol. 2019;234:17–24.
- Van den Eede A., Hermans K., Van den Abeele A., Floré K., Dewulf J., Vanderhaeghen W., Némeghaire S., Butaye P., Gasthuys F., Haesebrouck F.. The nasal vestibulum is the optimal sampling site for MRSA screening in hospitalised horses.. Vet. J. 2013;197:415–419.
- Maddox T.W., Scantlebury C.E., Clegg P.D., Dawson S., Pinchbeck G.L., Williams N.J.. A review of the characteristics and treatment of methicillin-resistant Staphylococcus aureus (MRSA) in the horse and a case series of MRSA infection in 4 horses.. Equine Vet. Educ. 2010;22:91–102.
- Weese J.S., Rousseau J., Traub-Dargatz J.L., Willey B.M., McGeer A.J., Low D.E.. Community-associated methicil-lin-resistant Staphylococcus aureus in horses and humans who work with horses.. J. Am. Vet. Med. Assoc. 2005;226:580–583.
- Hamidou Soumana I., Linz B., Harvill E.T.. Environmental Origin of the Genus Bordetella.. Front. Microbiol. 2017;8:28.
- Garcia-Cantu M.C., Hartmann F.A., Brown B.J.. Bordetella bronchiseptica and equine respiratory infections: A review of 30 cases.. Equine Vet. Educ. 2000;12:45–50.
- Vaid R.K., Shanmugasundaram K., Anand T., Bera B.C., Tigga M., Dedar R., Riyesh T., Bardwaj S., Virmani N., Tripathi B.N.. Characterization of isolates of Bordetella bronchiseptica from horses.. J. Equine Sci. 2018;29:25–31.
- Otto M.. Staphylococcus aureus toxins.. Curr. Opin. Microbiol. 2014;17:32–37.
- Masin J., Osicka R., Bumba L., Sebo P.. Bordetella adenylate cyclase toxin: A unique combination of a pore-forming moiety with a cell-invading adenylate cyclase enzyme.. Pathog. Dis. 2015;73:ftv075.
- Kwak Y.K., Vikström E., Magnusson K.E., Vécsey-Semjén B., Colque-Navarro P., Möllby R.. The Staphylococcus aureus alpha-toxin perturbs the barrier function in Caco-2 epithelial cell monolayers by altering junctional integrity.. Infect. Immun. 2012;80:1670–1680.
- Seilie E.S., Bubeck Wardenburg J.. Staphylococcus aureus pore-forming toxins: The interface of pathogen and host com-plexity.. Semin. Cell Dev. Biol. 2017;72:101–116.
- Ziesemer S., Eiffler I., Schönberg A., Müller C., Hochgräfe F., Beule A.G., Hildebrandt J.P.. Staphylococcus aureus α-Toxin Induces Actin Filament Remodeling in Human Airway Epithelial Model Cells.. Am. J. Respir. Cell Mol. Biol. 2018;58:482–491.
- Hasan S., Kulkarni N.N., Asbjarnarson A., Linhartova I., Osicka R., Sebo P., Gudmundsson G.H.. Bordetella pertussis Adenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers.. Infect. Immun. 2018;86:e00445-17.
- Laval K., Poelaert K.C.K., Van Cleemput J., Zhao J., Vandekerckhove A.P., Gryspeerdt A.C., Garré B., van der Meulen K., Baghi H.B., Dubale H.N.. The Pathogenesis and Immune Evasive Mechanisms of Equine Herpesvirus Type 1.. Front. Microbiol. 2021;12:662686.
- Kydd J.H., Smith K.C., Hannant D., Livesay G.J., Mumford J.A.. Distribution of equid herpesvirus-1 (EHV-1) in respiratory tract associated lymphoid tissue: Implications for cellular immunity.. Equine Vet. J. 1994;26:470–473.
- Gryspeerdt A.C., Vandekerckhove A.P., Garré B., Barbé F., Van de Walle G.R., Nauwynck H.J.. Differences in replication kinetics and cell tropism between neurovirulent and non-neurovirulent EHV1 strains during the acute phase of infection in horses.. Vet. Microbiol. 2010;142:242–253.
- Vandekerckhove A.P., Glorieux S., Gryspeerdt A.C., Steukers L., Duchateau L., Osterrieder N., Van de Walle G.R., Nauwynck H.J.. Replication kinetics of neurovirulent versus non-neurovirulent equine herpesvirus type 1 strains in equine nasal mucosal explants.. J. Gen. Virol. 2010;91:2019–2028.
- Baghi H.B., Laval K., Favoreel H., Nauwynck H.J.. Isolation and characterization of equine nasal mucosal CD172a + cells.. Vet. Immunol. Immunopathol. 2014;157:155–163.
- Allen G.. Advances in understanding of the pathogenesis, epidemiology and immunological control of equine herpesvirus abortion.. In: Nakajima H., Plowright W., editors. Equine Infectious Diseases: Proceedings of the Eighth International Conference. Newmarket: R&W Publishers; Suffolk, UK: 1999. pp. 129–146.
- Wilson W.D.. Equine herpesvirus 1 myeloencephalopathy.. Vet. Clin. N. Am. Equine Pract. 1997;13:53–72.
- Grinde B.. Herpesviruses: Latency and reactivation—Viral strategies and host response.. J. Oral Microbiol. 2013;5:22766.
- Slater J.D., Borchers K., Thackray A.M., Field H.J.. The trigeminal ganglion is a location for equine herpesvirus 1 latency and reactivation in the horse.. J. Gen. Virol. 1994;75:2007–2016.
- Van Cleemput J., Poelaert K., Laval K., Maes R., Hussey G.S., Van den Broeck W., Nauwynck H.J.. Access to a main alphaherpesvirus receptor, located basolaterally in the respiratory epithelium, is masked by ICJ.. Sci. Rep. 2017;7:16656.
- Vandekerckhove A., Glorieux S., Broeck W.V., Gryspeerdt A., van der Meulen K.M., Nauwynck H.J.. In vitro culture of equine respiratory mucosa explants.. Vet. J. 2009;181:280–287.
- Vairo S., Van den Broeck W., Favoreel H., Scagliarini A., Nauwynck H.. Development and use of a polarized equine upper respiratory tract mucosal explant system to study the early phase of pathogenesis of a European strain of equine arteritis virus.. Vet. Res. 2013;44:22.
- van Der Meulen K.M., Nauwynck H.J., Bí¶®rt W., Pensaert M.B.. Replication of equine herpesvirus type 1 in freshly isolated equine peripheral blood mononuclear cells and changes in susceptibility following mitogen stimulation.. J. Gen. Virol. 2000;81:21–25.
- Laval K., Favoreel H.W., Poelaert K.C., Van Cleemput J., Nauwynck H.J.. Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a+ Monocytic Cells upon Adhesion to Endothelial Cells.. J. Virol. 2015;89:10912–10923.
- van der Meulen K.M., Nauwynck H.J., Pensaert M.B.. Absence of viral antigens on the surface of equine herpesvi-rus-1-infected peripheral blood mononuclear cells: A strategy to avoid complement-mediated lysis.. J. Gen. Virol. 2003;84:93–97.
- Yang X., Forier K., Steukers L., Van Vlierberghe S., Dubruel P., Braeckmans K., Glorieux S., Nauwynck H.J.. Immobilization of pseudorabies virus in porcine tracheal respiratory mucus revealed by single particle tracking.. PLoS ONE. 2012;7:e51054.
- Beadling C., Slifka M.K.. How do viral infections predispose patients to bacterial infections?. Curr. Opin. Infect. Dis. 2004;17:185–191.
- Sender V., Hentrich K., Henriques-Normark B.. Virus-Induced Changes of the Respiratory Tract Environment Promote Secondary Infections With Streptococcus pneumoniae.. Front. Cell Infect. Microbiol. 2021;11:643326.
- Bin L., Kim B.E., Brauweiler A., Goleva E., Streib J., Ji Y., Schlievert P.M., Leung D.Y.. Staphylococcus aureus α-toxin modulates skin host response to viral infection.. J. Allergy Clin. Immunol. 2012;130:683–691.
- Ohnishi H., Miyake M., Kamitani S., Horiguchi Y.. The morphological changes in cultured cells caused by Bordetella pertussis adenylate cyclase toxin.. FEMS Microbiol. Lett. 2008;279:174–179.
- McNeil E., Capaldo C.T., Macara I.G.. Zonula occludens-1 function in the assembly of tight junctions in Madin-Darby canine kidney epithelial cells.. Mol. Biol. Cell. 2006;17:1922–1932.
- Stevens Lowe J.S., Anderson P.G.. Human Histology.. 4th ed. Mosby Elsevier; Maryland Heights, MO, USA: 2005. Chapter 3—Epithelial Cells; pp. 37–54.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists