# Pathogen Synergy Through Cross-Species Induction of Outer Membrane Vesicle Biogenesis

> **NIH NIH R21** · STATE UNIVERSITY OF NY,BINGHAMTON · 2020 · $214,410

## Abstract

Abstract
Bacteria have been cooperating and competing for all of evolutionary time. Only recently, however, have we
seriously begun to take this into account in the context of infectious disease mechanisms. The expanding ability
to study bacteria in complex consortia (i.e. how they normally live) has sparked a renewed appreciation for the
complexity of real bacterial populations and an examination of how they interact. Co-infection studies show that
pathogen communities are more virulent, and this aligns with epidemiological reports that connect multispecies
infections to worse patient outcomes. A common hypothesis is that this pathogen synergy comes about because
of competition and communication between multiple species at an infection site. We hypothesize that Outer
Membrane Vesicles (OMVs) serve as a major mediator of these interactions because they are known to facilitate
both competition and communication between bacteria (in addition to direct virulence against host cells).
We proposed a model in P. aeruginosa where OMV biogenesis is driven by the secretion and insertion of a self-
produced small molecule into the outer leaflet of the outer membrane. We recently showed that this molecule
could induce related species to overproduce OMVs when given at low concentration, and that those recipient
species produced their own OMV cross-inducing factors. This raised the possibility that cross-species induction
of OMV biogenesis could serve as a mechanism for multispecies communities to synergize for increased
virulence. Guided by strong preliminary data, we will pursue two specific aims to characterize how multiple
pathogens at an infection site might interact through cross-species induction of OMV biogenesis and what effects
this would have on host cells: (1) We will begin by testing for small molecule-induced OMV formation using the
known P. aeruginosa OMV-inducing compound PQS against a broad panel of important human pathogens likely
to encounter each other at an infection site. Our established methods have already identified several such
interactions among the γ-proteobacteria. We will then test whether actually growing species together (in contrast
to using monocultures with exogenous compounds as above) will result in increased OMV production for the
community. Preliminary results show that this is true for our pilot pairing of P. aeruginosa + E. coli. (2) OMVs
from mono- vs. co-culture will be tested for their cytotoxic potential against macrophage and lung epithelial cells
as well as their ability to degrade or sequester antibiotics (another disease-related function of OMVs). Preliminary
results with P. aeruginosa + E. coli co-culture OMVs show that cytotoxicity and induction of apoptosis are both
increased over monoculture OMVs, demonstrating feasibility of the approach and providing support for the
hypothesis that cross-species OMV induction may contribute to pathogen synergy.
Understanding pathogen interactions at infection sites is crit...

## Key facts

- **NIH application ID:** 10043365
- **Project number:** 1R21AI154086-01
- **Recipient organization:** STATE UNIVERSITY OF NY,BINGHAMTON
- **Principal Investigator:** Jeffrey Schertzer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $214,410
- **Award type:** 1
- **Project period:** 2020-06-29 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10043365

## Citation

> US National Institutes of Health, RePORTER application 10043365, Pathogen Synergy Through Cross-Species Induction of Outer Membrane Vesicle Biogenesis (1R21AI154086-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10043365. Licensed CC0.

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