Genetic Analysis of Acanthamoeba in Patients with Acanthamoeba Keratitis (GAP-AK) (IRAS 353842)

We want to look at the genetic make-up of Acanthamoeba, a microscopic organism, that can cause serious eye infections that can lead to blindness. We aim to look at the genetic make-up and their environment with an aim to improve treatments. Hidden in water, soil and even household dust, the microscopic organism Acanthamoeba is causing a growing number of sight-threatening eye infections. Researchers are using genomics to investigate why some Acanthamoeba species can invade the eye, resist treatment and, in severe cases, lead to permanent sight loss.

Although AK is rare, the number of cases in the UK has increased in recent years, particularly among contact lens users. Treatment usually involves intensive use of eye drops over many months. Unfortunately, treatment does not always work because Acanthamoeba can form highly resistant cysts that are difficult to eliminate. When treatment fails, patients may need a corneal transplant or, in very severe cases, surgical removal of the eye.

This study aims to improve our understanding of Acanthamoeba by examining its genetic makeup. Researchers will compare different types of Acanthamoeba, including strains that cause disease and those that do not, to identify the genes and proteins that help the organism survive and cause infection. The study will also investigate other microorganisms that may be present alongside Acanthamoeba and whether they affect how the infection develops or responds to treatment. The findings could help improve the diagnosis, treatment and prevention of this sight-threatening infection in the future.

Rationale

Current understanding of the Acanthamoeba species and strains responsible for AK in the UK remains incomplete. In addition, the genetic determinants of pathogenicity, disease progression, encystment and treatment resistance are not fully understood. This study will investigate the genomic diversity and mutational landscape of clinical and reference Acanthamoeba isolates and examine associated microorganisms that may influence disease severity. Improved understanding of these factors may support future development of improved diagnostics and treatments for AK.

Aims

This study aims to:

• characterise the genomics and mutational landscape of Acanthamoeba species associated with Acanthamoeba keratitis.
• investigate relationships between Acanthamoeba species, gene and protein expression, pathogenic mechanisms and disease severity.
• examine associations between Acanthamoeba-resistant microorganisms present in clinical samples and disease severity.
• identify genes and molecular pathways associated with pathogenicity, encystment and treatment resistance.

Primary Outcome

Whole genome sequencing of all known Acanthamoeba species in the UK.

Key Secondary outcome(s)

Identification of microbial associates in clinical samples.

Species, or mutation, correlation with disease severity and resistance.

Study Type

Observational

Cohort

Participant and Sample Information

Populations involved:

Participants with AK donating clinical eye scraping samples.

Countries of recruitment:

UK

Approximate participant or sample numbers (if applicable):

80

Key inclusion criteria:

Individuals over 16 with AK infection

Key exclusion criteria:

Children/under 16s
No AK diagnosis

Recruitment status:

Recruiting by invitation only.

Governance and Ethical Approval

Governance and oversight:

Study Sponsor: Wellcome Sanger Institute

All work conducted at the Wellcome Sanger Institute is reviewed and overseen by institutional Research Governance processes, ensuring compliance with ethical, legal, and regulatory requirements.

Ethical approval:

This study has been reviewed by the London – Hampstead NHS Research Ethics Committee. The study received REC approval on 29 April 2025.

IRAS 353842

REC reference: 25/PR/0460

Data and Sample Use

Data sharing:

Samples will be used exclusively for research into Acanthamoeba and associated microorganisms. No human genetic analysis will be performed. Any human DNA or RNA sequence incidentally generated during laboratory processing will be identified and removed bioinformatically prior to analysis and will not be shared.

Microbial genome sequencing data will be deposited in the European Nucleotide Archive (ENA).

IPD sharing statement

Deidentified individual participant-level data (IPD) will not be shared as part of this study.

Completion date

Ongoing

Further information

For enquiries about the scientific aims of this study or potential collaboration, please contact the relevant scientific programme at https://www.sanger.ac.uk/programme/tree-of-life/ or the Chief Investigator Michael Leroy Kwame Ansah at ma29@sanger.ac.uk

For enquiries relating to research governance, ethics, or regulatory oversight, please contact the Research Governance team at researchgovernance@sanger.ac.uk.