Activation of persistent Streptococcus equi subspecies zooepidemicus in mares with subclinical endometritis.
Abstract: Endometritis in horses caused by Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) may be underdiagnosed due to traditional diagnostic methods lacking sensitivity and specificity. We serendipitously identified a bacterial growth medium (bActivate) that appeared capable of inducing growth of dormant S. zooepidemicus, which subsequently allowed detection by standard diagnostics. To assess the effect of bActivate we compared its ability to activate dormant S. zooepidemicus in a group of potentially infected subfertile mares with phosphate-buffered saline (PBS). All mares had to test negative for S. zooepidemicus on a low-volume uterine lavage, be negative on endometrial cytology and without clinical signs of endometritis to be included in the investigation. The mares were instilled with bActivate or PBS in the uterus. Growth of S. zooepidemicus was induced by bActivate in 64% (16/25) and PBS in 8% (1/12) of the mares, respectively (p<0.002). In vitro studies supported that some strains of S. zooepidemicus were able to form persister cells tolerating 32-times of the minimal inhibitory concentration of penicillin compared to normal growing cells. Persister cells had not acquired penicillin resistance, but seemed to tolerate the antimicrobial due to dormancy. This is, to our knowledge, the first description of controlled growth induction of dormant bacteria from a subclinical infection. Moreover we demonstrated how endometritis can origin from a reservoir of dormant bacteria residing within the endometrium, and not only as an ascending infection. Further studies should aim at determining the prevalence of dormant S. zooepidemicus, impact of activation on diagnostic and treatment efficacy, uterine health and mare fertility.
Copyright © 2015 Elsevier B.V. All rights reserved.
Publication Date: 2015-06-11 PubMed ID: 26123371DOI: 10.1016/j.vetmic.2015.06.006Google 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
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 studies the effectiveness of a bacterial growth medium, called bActivate, in detecting a bacterial infection causing endometritis in horses. It has been found to be effective at inducing growth of dormant Streptococcus equi subspecies zooepidemicus, a bacteria typically under-diagnosed due to weak diagnostic methods.
Research Background
- Endometritis in horses is often caused by Streptococcus equi subspecies zooepidemicus (S. zooepidemicus).
- Existing diagnostic methods were often unsuccessful in pinpointing this bacterial infection due to their lack of sensitivity and specificity.
Objective of the Research
- The aim was to test a bacterial growth medium, bActivate, which was hypothesized to potentially awaken dormant S. zooepidemicus.
- This awakened bacteria could then be identified through standard diagnostic methods.
Methodology and Results
- The researchers compared the effectiveness of bActivate in activating dormant S. zooepidemicus in potentially infected, subfertile mares to phosphate-buffered saline (PBS).
- The tested mares had to meet several conditions for participating in the study: they had to test negative for S. zooepidemicus on a low-volume uterine lavage, be negative on endometrial cytology, and without clinical signs of endometritis.
- The mares were treated with either bActivate or PBS, after which the growth of S. zooepidemicus was induced in 64% of the mares treated with bActivate, compared to only 8% of those treated with PBS.
In Vitro Studies
- Supplemental laboratory studies supported that some strains of S. zooepidemicus could form persister cells that tolerated 32 times the minimal inhibitory concentration of penicillin compared to normal growing cells.
- These persister cells hadn’t gained resistance to penicillin; rather, they seemed to tolerate the antibiotic because they were dormant.
Implications of the Findings
- This is the first recorded instance of controlled growth induction of dormant bacteria from a subclinical infection.
- It’s been demonstrated that endometritis can originate from a reservoir of dormant bacteria within the endometrium, not only as an ascending infection.
- Future research should focus on determining the prevalence of dormant S. zooepidemicus, the impact of activation on diagnostic and treatment efficacy, uterine health, and mare fertility.
Cite This Article
APA
Petersen MR, Skive B, Christoffersen M, Lu K, Nielsen JM, Troedsson MH, Bojesen AM.
(2015).
Activation of persistent Streptococcus equi subspecies zooepidemicus in mares with subclinical endometritis.
Vet Microbiol, 179(1-2), 119-125.
https://doi.org/10.1016/j.vetmic.2015.06.006 Publication
Researcher Affiliations
- The Fertility Clinic, Rigshospitalet, Section 4071, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: morten.petersenr@gmail.com.
- Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Stigboejlen 4, DK-1870 Frederiksberg C, Denmark.
- Section of Veterinary Reproduction and Obstetrics, Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej 68, DK-1870 Frederiksberg C, Denmark.
- Hagyard Equine Medical Institute, Lexington, Kentucky, USA.
- Ansager Large Animal Hospital, Gartnerhaven 5, 6823 Ansager, Denmark.
- Maxwell H. Gluck Center for Equine Research, University of Kentucky, Lexington, USA.
- Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Stigboejlen 4, DK-1870 Frederiksberg C, Denmark.
MeSH Terms
- Animals
- Asymptomatic Infections
- Endometritis / diagnosis
- Endometritis / microbiology
- Endometritis / veterinary
- Endometrium / microbiology
- Female
- Horse Diseases / diagnosis
- Horse Diseases / microbiology
- Horses
- Microbial Sensitivity Tests / veterinary
- Sensitivity and Specificity
- Streptococcal Infections / diagnosis
- Streptococcal Infections / microbiology
- Streptococcal Infections / veterinary
- Streptococcus equi / growth & development
- Streptococcus equi / isolation & purification
Citations
This article has been cited 20 times.- Bergmann R, Schroedl W, Müller U, Baums CG. A distinct variant of the SzM protein of Streptococcus equi subsp. zooepidemicus recruits C1q independent of IgG binding and inhibits activation of the classical complement pathway. Virulence 2023 Dec;14(1):2235461.
- Boni R, Cecchini Gualandi S. Relationship between Oxidative Stress and Endometritis: Exploiting Knowledge Gained in Mares and Cows. Animals (Basel) 2022 Sep 13;12(18).
- D'Agostino A, Di Palma T, Cecchini Gualandi S, Boni R. Fluorescence Spectroscopy for the Diagnosis of Endometritis in the Mare. Animals (Basel) 2022 Apr 29;12(9).
- Nocera FP, D'Eletto E, Ambrosio M, Fiorito F, Pagnini U, De Martino L. Occurrence and Antimicrobial Susceptibility Profiles of Streptococcus equi subsp. zooepidemicus Strains Isolated from Mares with Fertility Problems. Antibiotics (Basel) 2021 Dec 27;11(1).
- Borlee GI, Lakin SM, Kapuscinski ML, Abdo Z, Stenglein MD, McCue PM, Borlee BR. Complete Genome Sequences of Eight Streptococcus equi subsp. zooepidemicus Strains Isolated from Mares in Estrus with Endometritis. Microbiol Resour Announc 2021 Jul;10(26):e0132120.
- Léon A, Castagnet S, Maillard K, Paillot R, Giard JC. Evolution of In Vitro Antimicrobial Susceptibility of Equine Clinical Isolates in France between 2016 and 2019. Animals (Basel) 2020 May 7;10(5).
- Schöniger S, Schoon HA. The Healthy and Diseased Equine Endometrium: A Review of Morphological Features and Molecular Analyses. Animals (Basel) 2020 Apr 5;10(4).
- Canisso IF, Segabinazzi LGTM, Fedorka CE. Persistent Breeding-Induced Endometritis in Mares - a Multifaceted Challenge: From Clinical Aspects to Immunopathogenesis and Pathobiology. Int J Mol Sci 2020 Feb 20;21(4).
- Skive B, Rohde M, Molinari G, Braunstein TH, Bojesen AM. Streptococcus equi subsp. zooepidemicus Invades and Survives in Epithelial Cells. Front Cell Infect Microbiol 2017;7:465.
- Siemieniuch MJ, Szóstek AZ, Gajos K, Kozdrowski R, Nowak M, Okuda K. Type of Inflammation Differentially Affects Expression of Interleukin 1β and 6, Tumor Necrosis Factor-α and Toll-Like Receptors in Subclinical Endometritis in Mares. PLoS One 2016;11(5):e0154934.
- Yi L, Wang Y, Ma Z, Lin HX, Xu B, Grenier D, Fan HJ, Lu CP. Identification and characterization of a Streptococcus equi ssp. zooepidemicus immunogenic GroEL protein involved in biofilm formation. Vet Res 2016 Apr 18;47:50.
- Vallejo-Soto P, Dorado J, Herrera-García R, Álvarez-Delgado C, Gómez-Laguna J, Santiago Á, Manrique M, González Ariza A, León Jurado JM, Hidalgo M, Ortiz I. Histomorphometric Analysis of the Endometrium of Jennies (Equus asinus) and Mares (Equus caballus) in Estrus: Anatomical Differences and Possible Reproductive Implications. Animals (Basel) 2026 Jan 4;16(1).
- Hardefeldt L, Thomas K, Page S, Norris J, Browning G, El Hage C, Stewart A, Gilkerson J, Muscatello G, Verwilghen D, van Galen G, Bauquier J, Cuming R, Reynolds B, Whittaker C, Wilkes E, Clulow J, Burden C, Begg L. Antimicrobial prescribing guidelines for horses in Australia. Aust Vet J 2025 Dec;103(12):781-889.
- Fehin B, Scott CJ, Arango-Sabogal JC, de Mestre AM, Mouncey R. Associations between endometrial swab bacteriology and cytology findings and live foal rates in Thoroughbred broodmares in the United Kingdom. Equine Vet J 2026 Mar;58(2):348-358.
- da Silva-Álvarez E, Gómez-Arrones V, Correa-Fiz F, Martín-Cano FE, Gaitskell-Phillips G, Carrasco JJ, Rey J, Aparicio IM, Peña FJ, Alonso JM, Ortega-Ferrusola C. Metagenomic and proteomic analyses reveal similar reproductive microbial profiles and shared functional pathways in uterine immune regulation in mares and jennies. PLoS One 2025;20(4):e0321389.
- Wang Z, Zeng S, Wang Y, Wang T, Qu H, Zhu Y, Li J. Reproductive Disorders in Donkeys: Current Evidence and Update. Animals (Basel) 2024 Aug 28;14(17).
- Kabir A, Lamichhane B, Habib T, Adams A, El-Sheikh Ali H, Slovis NM, Troedsson MHT, Helmy YA. Antimicrobial Resistance in Equines: A Growing Threat to Horse Health and Beyond-A Comprehensive Review. Antibiotics (Basel) 2024 Jul 29;13(8).
- Gil-Miranda A, Macnicol J, Orellana-Guerrero D, Samper JC, Gomez DE. Reproductive Tract Microbiota of Mares. Vet Sci 2024 Jul 18;11(7).
- Heil BA, van Heule M, Thompson SK, Kearns TA, Oberhaus EL, King G, Daels P, Dini P, Sones JL. Effect of Sampling Method on Detection of the Equine Uterine Microbiome during Estrus. Vet Sci 2023 Nov 8;10(11).
- Tukia E, Hallman I, Penttilä M, Hänninen S, Kareskoski M. RNA in situ hybridization of Escherichia coli in equine endometrial biopsies. Front Vet Sci 2023;10:1186051.
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
