# BACTERIAL IGA PROTEASES

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 1993 · $185,661

## Abstract

The objective of the proposed research is to define interactions that
occur between bacteria and the mucosal cell surface and to relate these
to mechanisms involved in disease.   We are currently studying a group of
bacterial proteases, produced by different serogroups of Haemophilus
influenzae and by Streptococcus sanguis, that cleave human IgA1, in order
to understand the role of these enzymes in infection.  We propose to
elucidate how the proteases interact with the IgA substrate by expressing
the IgA heavy chain from cloned cDNA and using it, or mutant variants as
a substrate.  We also want to determine the basis for cleavage
specificity of the H.influenzae proteases which fall into two main types
based on the specific bond cleaved in the IgA hinge region.  Hybrids will
be constructed between the two gene types to identify the determinants of
specificity.  The IgA proteases are secreted outside the cell in a
process that is dependent on the carboxyl terminal region of the primary
gene product.  This region is thought to form a pore in the membrane. We
want to understand the role of this segment in secretion and will
approach the problem through a detailed genetic analysis just this
portion of the gene.  We have observed that growth of H.influenzae in
human milk blocks secretion of IgA protease, resulting in aggregation of
the organism.  The effect is due to IgA1 in the milk.  We will examine
this effect further to see if it more accurately mimics the in vivo
conditions than growth in synthetic medium. We will use a series of iga
gene hybrids to identify sites in the enzymes that are highly antigenic
in vivo with the hope that such knowledge might be useful in vaccine
development.  We will use human lung epithelial cells , cultured in the
presence of human IgA, to study the role of H. influenzae IgA1 protease
in bacterial attachment and colonization.

## Key facts

- **NIH application ID:** 3129952
- **Project number:** 2R01AI020337-07A2
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **SAM.gov UEI:** C1F5LNUF7W86
- **Principal Investigator:** ANDREW WRIGHT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $185,661
- **Award type:** 2
- **Project period:** 1983-08-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129952

## Citation

> US National Institutes of Health, RePORTER application 3129952, BACTERIAL IGA PROTEASES (2R01AI020337-07A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129952. Licensed CC0.

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