This article and associated images are based on a poster originally authored by Rory Triniman, Tim Lindsay, Nelson Lam, and Eddie French and presented at ELRIG Drug Discovery 2025 in affiliation with Veirulence.
This poster is being hosted on this website in its raw form, without modifications. It has not undergone peer review but has been reviewed to meet AZoNetwork's editorial quality standards. The information contained is for informational purposes only and should not be considered validated by independent peer assessment.
Background
Antibiotics are the only treatment option for bacterial infections, targeting just a few essential systems. However, bacterial virulence factors (VFs) have increasingly been validated as drug targets with strong clinical relevance.1-3 Neutralizing VFs have potential as a new modality to address the challenge of antibiotic resistance.
Swarming: A virulent lifestyle
Opportunistic pathogens dramatically change phenotypes for different “lifestyle” choices – motile and virulent or biofilm and chronic persistence. These lifestyle switches are regulated at a global and localized level by c-di-GMP.
Swarming motility is a validated acute virulence determinant, with a swarming phenotype observed in most infection isolates.
Table 1. Swarming phenotype prevalence in a cohort of P. aeruginosa clinical isolates.4 Source: Table adapted from Murray et al., 2010
| Culture Site (P. aeruginosa) |
Swarm-positive phenotype [n (%)] |
| Respiratory (136) |
75 (57) |
| Urine (65) |
41 (63) |
| Wound (22) |
16 (76) |
| Blood (14) |
11 (85) |
| Total (227) |
143 (63) |
Veirulence is developing a first-in-class small molecule that targets a core genome regulator of c-di-GMP to treat acute Gram-negative bloodstream infections.
The mechanism results in dose-dependent inhibition of swarming but also provides additional therapeutic benefits by preventing a virulent lifestyle in P. aeruginosa.
Swarming inhibition vs MDR P. aeruginosa clinical isolates
Figure 1. Dose-dependent swarming inhibition by VEI-0026 against multi-drug resistant (MDR) P. aeruginosa clinical isolate (trachea). IC50 ~200 nM. The result is representative of efficacy against MDR isolates of sputum, urinary tract, skin, and wound infections. All tested isolates are resistant to β-lactams (including carbapenems), aminoglycosides, and fluoroquinolones. Image Credit: Image courtesy of Rory Triniman et al., in partnership with ELRIG (UK) Ltd.
MIC values (μg/mL):
| Compounds |
PAO1 |
| VEI-0026 |
>80* |
| Ampicillin |
>64 |
| Ceftazidime |
2 |
| Ciprofloxacin |
<0.125 |
| Tobramycin |
0.5 |
* μM
Figure 2. (Table) MIC values for VEI-0026 and common antibiotics. An MIC was not obtained for VEI-0026 at any tested concentration. (Graph) VEI-0026 does not inhibit the growth of P. aeruginosa at concentrations 10x higher than swarming EC100; prevention of swarming is not a result of cytotoxicity but selective disruption to c-di-GMP signalling. Image Credit: Image courtesy of Rory Triniman et al., in partnership with ELRIG (UK) Ltd.
Figure 3. Transcriptomic analysis of P. aeruginosa on a swarming plate treated with VEI-008 (vs untreated). Significant differentially expressed genes that play a key role within clinically relevant systems - T3SS, elastases, swarming, and antibiotic resistance - are highlighted to demonstrate a broad suppressive effect on P. aeruginosa acute virulence behavior. Image Credit: Image courtesy of Rory Triniman et al., in partnership with ELRIG (UK) Ltd.
Discussion
A growing body of literature is showing VFs have excellent therapeutic potential. However, research has focused on specific VFs to target. Here, we introduce our first-in-class approach, which disrupts c-di-GMP signalling and causes a broad suppression of a highly virulent and resistant lifestyle, characterized by swarming. Veirulence is in lead optimization with its lead series.
Future work will focus on mechanisms of potentiation with antibiotics and the development of translational animal models in our area of interest.
References
- Ciofu O, Johansen HK, Høiby N. (2022). LasB elastase expression contributes to airway colonization and early-stage infection in cystic fibrosis patients with Pseudomonas aeruginosa.
- Valik, J.K., et al. (2024). Genomic virulence markers are associated with severe outcomes in patients with Pseudomonas aeruginosa bloodstream infection. Communications Medicine, 4(1). DOI: 10.1038/s43856-024-00696-4. https://www.nature.com/articles/s43856-024-00696-4.
- Llanos, A., et al. (2023). Higher levels of Pseudomonas aeruginosa LasB elastase expression are associated with early-stage infection in cystic fibrosis patients. Scientific Reports, [online] 13(1), p.14208. DOI: 10.1038/s41598-023-41333-9. https://www.nature.com/articles/s41598-023-41333-9.
- Murray, T.S., Ledizet, M., and Kazmierczak, B.I. (2010). Swarming motility, secretion of type 3 effectors, and biofilm formation phenotypes were exhibited within a large cohort of Pseudomonas aeruginosa clinical isolates. Journal of Medical Microbiology, 59(5), pp.511–520. DOI: 10.1099/jmm.0.017715-0. https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.017715-0.
About Veirulence Ltd.
Veirulence Ltd. is a UK-based biopharmaceutical startup pioneering a first-in-class, non-antibiotic therapeutic approach to combat bacterial infections and the growing global challenge of antimicrobial resistance (AMR).
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Last Updated: Dec 12, 2025