# Biogenesis of surface-exposed lipoproteins in Gram-negative bacteria

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $325,248

## Abstract

PROJECT SUMMARY
The outer membrane in Gram-negative bacteria is a dynamic interface that mediates bacterial interaction
with the host by displaying proteins on its surface. The recently discovered surface-exposed lipoproteins
(SLPs) play critical roles in pathogenesis, including iron acquisition, adhesion, immune evasion and serve
as valuable vaccine targets. Despite their biomedical importance, the mechanism underlying lipoprotein
localization to the cell surface is the least understood aspect of bacterial envelope biogenesis. The long-
term goal of research in my laboratory is to define the mechanism of lipoprotein targeting and export to
the bacterial cell surface. We expect that groups of lipoproteins with similar topologies and/or structural
features share dedicated assembly pathways. Improving our understanding of molecular determinants
for export will enable the development of predictive computational models for lipoprotein localization and
genomic identification of SLPs. One SLP subfamily includes lipoproteins that depend on a partner β-
barrel outer membrane protein (OMP) for surface exposure. We discovered the RcsF lipoprotein in
Escherichia coli as the first example of this type. We further discovered that the highly conserved and
essential β-barrel assembly machinery (Bam) complex plays a critical role in the biogenesis of RcsF,
uncovering the novel function of the Bam complex in lipoprotein biogenesis. Here, we propose to use a
combination of genetics, biochemistry, and mass spectrometry approaches to identify the molecular
mechanism by which the Bam complex displays lipoproteins on the cell surface. We are specifically
interested in how the Bam complex recognizes lipoproteins and coordinates lipoprotein surface exposure
with OMP assembly. The completion of the proposed studies will substantially expand our understating
of biogenesis of SLPs and the Gram-negative cell envelope. The knowledge gained from the proposed
studies will enable formulation of computational models for identification of novel SLPs and much-needed
vaccines targets.

## Key facts

- **NIH application ID:** 10246940
- **Project number:** 5R01GM133904-03
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Anna Konovalova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $325,248
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246940

## Citation

> US National Institutes of Health, RePORTER application 10246940, Biogenesis of surface-exposed lipoproteins in Gram-negative bacteria (5R01GM133904-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10246940. Licensed CC0.

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