UWS research into the debilitating eye infection Acanthamoeba Keratitis (AK) has significantly impacted on the handling of contact lenses and their cases to the benefit of the world's 125 million lens users.
The UWS team was led by Professor Fiona Henriquez, whose research interests focus on infections by opportunistic eukaryotic pathogens and in particular, the Acanthamoeba species. These microorganisms are difficult to treat due to the inefficacy of current medicines and the resistance of Acanthamoeba to many compounds. Some compounds that have been shown to be effective are also highly toxic to human cells. This pioneering research, undertaken in partnership with the University of Strathclyde, led to the initial steps taken to develop a novel high-throughput assay system to assess the efficiency of the inhibitory compounds. This assay has facilitated Professor Henriquez’s current research.
In 2008 Henriquez et al., published a study that clearly presented the challenges faced in the treatment of Acanthamoeba keratitis (AK). In this research, the resistance of Acanthamoeba to several anti-tubulin compounds, including potent anti-neoplastics (paclitaxel, vinblastine) is described, thus illustrating its resilience to the most potent inhibitors to eukaryotic cells. This is despite the fact that tubulin is one of the most conserved proteins between species and the high resistance phenomenon was found to be due to different amino acids in critical binding areas of the Acanthamoeba protein. Significantly, these amino acid differences may be exploited in future studies to create a specific compound that can target only Acanthamoeba tubulin, thus reducing the toxic effects in the human host. This early research was followed up in 2009 when Henriquez et al., described the characterisation of alternative oxidase (AOX), which is present in Acanthamoeba, but not in the human host. AOX is a mechanism through which Acanthamoeba can overcome inhibitory pressures from toxic compounds and, therefore, it is important to take this into consideration for future drug design.
Professor Henriquez‘s work has also focused on exploiting metabolic differences between Acanthamoeba and the human host and she has directed a number of UWS PhD students in this area. This work has characterised the histidine biosynthesis and shikimate pathways present in Acanthamoeba but absent from the human host. Her work has demonstrated that Acanthamoeba growth can be inhibited by compounds that block either of the pathways and has already been protected by two published patents.
In addition to the challenge of the development of an effective treatment, investigation into contact lens user compliance highlighted the issue that the contact lens end-user must be adequately informed of the potential risks of Acanthamoeba contamination of contact lenses. For this reason, Professor Henriquez organised an event at the British Science Festival in 2012 to highlight the potential risks of microbial contamination in contact lenses to the public. She brought together a multidisciplinary team of four experts; an optician who delivered tutorials about the correct use of contact lenses; an engineer to explain why contact lenses and their cases are ideal surfaces for microbial growth: an immunologist with expertise in immune responses in the eye; and herself, a microbiologist, who focused on the challenges faced in treating Acanthamoeba infection.
There are 125 million contact lens wearers worldwide and potentially all are at risk of Acanthamoeba infection and therefore this research has a global impact.
Following publication of her research findings on the Acanthamoeba keratitis in 2008, Professor Henriquez actively engaged in dialogue with the commercial arm of the world famous Moorfields Eye Hospital NHS Foundation Trust, Moorfields Pharmaceuticals. The company specialises in the manufacture and development of sterile liquid products and Ophthalmic Specials products. Moorfields agreed to conduct a survey amongst Ophthalmologists, which confirmed the unanimous agreement that an effective pharmaceutical product was required to treat Acanthamoeba infection.
The impact of this research has been in 4 areas:
PATENT: Roberts, C.W. Ingram, P.R. HENRIQUEZ, F.L. & Roberts, F. (2006). Antimicrobial Compounds PCT/GB2006/000875.
PATENT: HENRIQUEZ, F.L & Roberts, C.W. (2008). Antiprotozoal compounds. UK patent application PCT/GB/2009/051197.
BCLA Adoption of new “no water” labeling and letter from the Artist, who was inspired to design these labels from the ‘Microbes in contact lenses’ event at the British Science Festival 2012.
This publication is in a highly ranked journal in the subject area (number 3 in citations and number 7 ranked by Eigenscore). It has revolutionized how Acanthamoeba viability is assessed. Before this publication Acanthamoeba assessment was slow and reliant of the fact that Acanthamoeba can feed on bacteria. This new method is suited for high through put assays without the need for a co culture of organisms. Since its publication in a subject focused journal it has been cited 37 times and it is now routinely used in laboratories worldwide, including the CDC.
This publication is in the number 1 journal in pharmacology and pharmacy for both citations and by Eigenfactor score ranking. It is the first study into genetic factors in Acanthamoeba that influence its resistance to toxic molecules that are used as herbicides, anti-neoplastics and anti-helminthics. Since its publication it has been cited 15 times in journals concerning medicinal chemistry and biotechnologies at an international level.
This publication is in a highly respected journal for parasitology (ranked 6 out 63, Eigenscore). It is specific to Acanthamoeba research and at the time of publication offered a unique insight into the makeup of the Acanthamoeba genome, including intron mapping and the existence of polymorphisms.