Biofilm formation explains resistance of equine recurrent uveitis to treatment – study

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Equine Recurrent Uveitis (ERU), a common eye condition in horses, is a biofilm-associated leptospiral infection, researchers show.
Image by Pezibear

Equine Recurrent Uveitis (ERU), which can lead to blindness in horses, is a biofilm-associated leptospiral infection within the eye, researchers in Germany report.

The fact the leptospira form a biofilm explains the typical clinical course of infections, which include apparent immune evasion and the ineffectiveness of antibiotics.

ERU causes painful inflammatory attacks in affected eyes. The bacterial disease is considered a late consequence of systemic leptospirosis.

ERU affects up to 10% of all horses in Europe and up to 25% in the United States. Both eyes are affected in about 25-50% of horses.

In horses, recurrent uveitis can occur at unpredictable intervals over many years and usually leads to blindness, despite intensive conservative therapy.

In European horses without a leopard coat pattern, the most effective way to prevent further episodes and preserve vision is the surgical removal of the vitreous – a procedure known as a vitrectomy.

The vitreous body, which contains collagen fibrils, consists of 98-99% water, and provides optimal conditions for the biofilm production of Leptospira.

After a properly performed vitrectomy, which has been routinely performed for more than 30 years in horses with ERU, the control of inflammation is seen in 90 to 97% of horses.

Uveitis in horses with a leopard coat pattern manifests differently, and typically does not appear to be as painful, researchers say.
Uveitis in horses with a leopard coat pattern manifests differently, and typically does not appear to be as painful, researchers say. Image by B Snuffleupagus

By contrast, uveitis in horses with a leopard coat pattern manifests differently. The condition in affected horses typically does not appear to be as painful. Leptospiral infection within the eye is rarely confirmed, suggesting a different disease process.

Kerstin Ackermann and her fellow researchers at Ludwig-Maximilians-University in Munich noted that diagnostic tests on removed vitreous tissue have identified culturable Leptospira species, anti-Leptospira antibodies, and lipL32 – a major immunogen during leptospiral infection.

“Despite this clear evidence of leptospiral involvement, the systemic administration of antibiotics in infected horses is ineffective at resolving ERU,” the study team wrote in the journal Microorganisms.

“This syndrome of chronic recurrent inflammation, which is unresponsive to antibiotic therapy, combined with apparent bacteria evading the immune response, is consistent with a biofilm-associated infection,” they said.

In their paper, the researchers described laboratory tests performed on vitreous samples removed from horses whose history and clinical findings indicated Leptospira-induced uveitis in a bid to detect the various known stages of biofilm formation.

The vitrectomies to obtain the samples were performed as a therapeutic procedure for the 32 animals at the Equine Clinic at the universities.

All known steps of biofilm formation were confirmed in the samples, including individual Leptospira species, leptospiral microcolonies and dense roundish accumulations of Leptospira species. In many instances, spirochetes were surrounded by an extracellular substance.

“Taken together,” they said, “data from the present study show that ERU is a biofilm-associated intraocular leptospiral infection, which best explains the typical clinical course.”

They said future studies should further differentiate biofilm formation in the equine vitreous, analyze the composition of this biofilm, and provide insights for other biofilm-associated infections.

The authors, discussing their findings, noted that six criteria have been established to describe biofilm-associated infections. ERU, they said, fulfilled all criteria described for biofilm-associated infections.

“The clinical signs and chronic disease course of ERU, as well culturable Leptospira species in vitreous samples from these eyes, despite high vitreal antibody titers, apparent immune evasion, and ineffectiveness of antibiotics, fulfill all the criteria of a biofilm-associated infection.

“The previously known steps of biofilm formation have hereby been demonstrated in vitreous samples from equine eyes suffering from recurrent uveitis,” they said. “Thus, we conclude that ERU is a spontaneous disease due to in vivo biofilm formation by Leptospira spp.”

The study team comprised Ackermann, Rebecca Kenngott, Monica Settles, Hartmut Gerhards, Johann Maierl and Bettina Wollanke.

Ackermann, K.; Kenngott, R.; Settles, M.; Gerhards, H.; Maierl, J.; Wollanke, B. In Vivo Biofilm Formation of Pathogenic Leptospira spp. in the Vitreous Humor of Horses with Recurrent Uveitis. Microorganisms 2021, 9, 1915. https://doi.org/10.3390/microorganisms9091915

The study, published under a Creative Commons License, can be read here

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