# Role of Yersinia pestis Ail-host ligand interactions in plague

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $450,096

## Abstract

Yersinia pestis, is the etiologic agent of plague, a disease that has killed millions of people
during massive pandemics and persists worldwide. The pathogenicity of Y. pestis is largely
dependent upon its ability to thwart the defenses of its host and to overwhelm it with massive
growth. Two surface-exposed outer membrane proteins, Adhesion invasion locus (Ail) and
Plasminogen activator (Pla) play a critical role in this process. This project focuses on Ail and its
role in promoting Y. pestis pathogenesis. Ail is required for complement resistance, efficient
attachment to host cells, Yop injection and for virulence in rodent models of bubonic, septicemic
and pneumonic plague. Ail binds several host ligands including fibronectin, laminin and C4b-
binding protein. We have recently identified vitronectin (Vn) as a new key ligand of Ail. Vn is a
multifunctional protein with roles in cell adhesion and complement control. Vn also binds and
stabilizes Plasminogen activator inhibitor 1 (PAI-1), a potent regulator of coagulation and
fibrinolysis. Ail recruits Vn to the bacterial surface and promotes its degradation by Pla. The
studies outlined in this proposal will: (i) use ligand-based NMR binding studies to define the Ail-
Vn interaction at the molecular level; (ii) use bacterial cell-based and biochemical assays to
define the role of the Ail-Vn interaction in fibrinolysis, complement resistance, cell attachment
and Yop injection; and (iii) define the role of the Ail-Vn interaction in a murine model of
septicemic plague. Ail is currently a target for therapy development and understanding how it
functions is critical to this effort.

## Key facts

- **NIH application ID:** 9850923
- **Project number:** 5R01AI130009-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Gregory V Plano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,096
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850923

## Citation

> US National Institutes of Health, RePORTER application 9850923, Role of Yersinia pestis Ail-host ligand interactions in plague (5R01AI130009-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9850923. Licensed CC0.

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