# Macrorecombination in isolated cell pairs via natural genetic transformation

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $444,666

## Abstract

Abstract /Summary:
Streptococcus pneumoniae (pneumococcus) is a major global bacterial human pathogen, causing
~1 million deaths annually worldwide, due to pneumonia, sepsis, and meningitis. Two strategies
are used to combat such infections. Antibiotics can often cure such infections, and vaccines are
used to reduce the circulating populations of the most dangerous serotypes. However, both
strategies are failing at an increasing rate. Antibiotic resistant strains are continually arising and
spreading globally; vaccination effectiveness is also under challenge, as serotypes not targeted
by current vaccine formulations are continually arising and rapidly replacing the targeted ones.
The cause of these failures is transfer of multiple foreign genes into the bacteria, but the
mechanisms that create the new infectious and resistant strain types are unclear. Transfer events
are of two types, named as micro- and macro-recombination events. The micro events, involving
dozens to several thousands of base pairs, are consistent with the known properties of gene
transfer by transformation in pneumococcus. However, more significant events involve transfer of
multiple blocks of tens of thousands of nucleotides, sometimes all from a single donor strain.
These macro-recombination events were difficult to reconcile completely with any known
mechanism of gene transfer - whether conjugation, transduction, or transformation. This project
would use microfluidics to create numerous small chambers (droplets) within which attacker-
target interactions can be studied and characterized for the first time at both the cellular and
molecular levels, both by identifying the participant cells and by tracing all gene exchange events
at full genome scale and 200-bp resolution.
Medical Relevance. Most pathogenic streptococci share the mechanism of gene transfer by
natural genetic transformation. Genetic transformation is an important path for genetic flexibility
in pneumococcus, where it is documented as key to vaccine escape and creation and spread of
new drug-resistance genes. Because Streptococcus pneumoniae is a model organism for the
study of DNA uptake, this work on the mechanism that transfers unexpectedly large blocks of
genes between strains or species will have broad impacts on understanding and targeting the
many similar peptide regulated gene exchange systems among Gram positive bacteria that are
often associated with the ability of these bacteria to cause disease.

## Key facts

- **NIH application ID:** 10291368
- **Project number:** 1R01AI155812-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** David Eddington
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $444,666
- **Award type:** 1
- **Project period:** 2021-05-21 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10291368

## Citation

> US National Institutes of Health, RePORTER application 10291368, Macrorecombination in isolated cell pairs via natural genetic transformation (1R01AI155812-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10291368. Licensed CC0.

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