# Biological and structural diversity of bacterial type IV secretion systems

> **NIH NIH R35** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $464,958

## Abstract

PROJECT SUMMARY
The transmission of macromolecules across biological membranes is a fundamental process in all cells. In the
earliest studies of genetic exchange in bacteria dating back to the 1940's, the F plasmid (then termed `sex
factor') was shown to self-transfer and, through recombination, mediate the transfer of the entire E. coli
chromosome to recipient bacteria. In the ensuing ~75 years, studies established the broad medical importance
of F and other mobile genetic elements (MGEs) in the shaping of bacterial genomes and as vectors for
dissemination of antibiotic resistance and other fitness traits among bacterial populations. MGEs also encode
conjugative pili or other cell surface adhesins, which promote intercellular contacts necessary for DNA transfer
and establishment robust, antibiotic-resistant biofilm communities. MGEs are transmitted intercellularly through
nanomachines termed type IV secretion systems (T4SSs). The T4SSs are present in most if not all bacterial
species, where they have functionally diversified into two large subfamilies, the DNA transfer or conjugation
systems and the `effector translocators' that translocate effector proteins into eukaryotic host cells as a critical
feature of infection processes. Over the past 27 years, my group has used molecular, genetic and biochemical
approaches to identify many mechanistic and architectural features of T4SSs, including the first view of the
translocation route for a DNA substrate through a T4SS. We have consistently implemented emerging
technologies, and just within the past 1½ years we began to solve T4SS structures at unprecedented
resolution by in situ cryoelectron tomography (CryoET). These new structures are significantly advancing the
field, but also are raising important new questions relating to underlying mechanisms and signals governing i)
assembly of envelope-spanning T4SS channels and conjugative pili, ii) early-stage substrate recruitment and
processing reactions, and iii) establishment of direct contacts (mating junctions) with bacterial and eukaryotic
cells. Moving forward, we will address these fundamental questions by (1) continuing to solve novel structures
encoded by the E. coli F T4SS using in situ CryoET, biochemical fractionation, super-resolution fluorescence
microscopy, and single-particle CryoEM, (2) defining contributions of the newly visualized ATPase energy
center positioned at the channel entrance in binding and unfolding substrates and dissociating accessory
factors using in vivo and in vitro biochemistry and ultrastructural approaches, (3) exploring the roles of
conjugative pili and cell surface adhesins in formation and disassembly of mating junctions using cytological,
biochemical and biophysical approaches, and (4) exploiting our development of distinct model systems to
identify mechanistic themes and specialized mechanisms. We will continue to draw on the expertise of our
close collaborations for a `team-science' and multidisciplinary focu...

## Key facts

- **NIH application ID:** 9944615
- **Project number:** 5R35GM131892-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** PETER j. CHRISTIE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $464,958
- **Award type:** 5
- **Project period:** 2019-06-07 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944615

## Citation

> US National Institutes of Health, RePORTER application 9944615, Biological and structural diversity of bacterial type IV secretion systems (5R35GM131892-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944615. Licensed CC0.

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