# A Multi-Omics Approach to the Examination of Bacterial Co-pathogens

> **NIH NIH U19** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $787,248

## Abstract

Polymicrobial infections have been linked to important human diseases including chronic wound infections,
lung infections, and bacteremia, and can involve different species of bacteria, or bacteria and viruses, or
bacteria and eukaryotes. Although the existence of co-pathogens in certain types of disease is established, the
complexity of studying co-pathogen interactions using models of pathogenesis has limited our understanding of
the role of the different pathogens in these diseases. The scientific premise of the proposed studies is that
although polymicrobial infections are linked to infectious diseases, prior experimental studies have focused on
single pathogens and have typically not considered the host:pathogen interactions in the presence of co-
pathogens or with other members of the host's microbiota. Thus, we will consider not only the impact of co-
pathogens on diarrheal illness and lung infections, but will also expand traditional laboratory assays, as well as
tissue culture and mouse models to more closely recapitulate the complexity of host:pathogen interactions. We
will investigate Aeromonas, E. coli, and/or Shigella in diarrheal co-infections, and the contributions of influenza
virus and Streptococcus pneumoniae to respiratory co-infections. In Aim 1 we will use comparative genomics
and metagenomics to provide insight into whether there are genes/genotypes, or microbial communities
associated with diarrhea and/or co-pathogen interactions of these diarrheal pathogens. In Aim 2 we will further
investigate the significance of diarrheal co-pathogens using dual transcriptomics on both the host and bacterial
sides to study the impact of co-pathogen interactions in human intestinal enteroids and a mouse model with a
simplified intestinal microbiota. In Aim 3, we will diversify our studies of co-infections by characterizing the
impact of influenza virus on S. pneumoniae infection of the respiratory tract by performing dual transcriptional
analyses with an ex vivo human lung epithelial cell model and an in vivo mouse model of lung infection. Our
central hypothesis is that the interaction of multiple pathogens, bacterial-bacterial or bacterial-viral, can result
in altered patterns of virulence of each of the pathogens, which will in turn influence interactions with the host,
and have a significant role in the disease outcome. We further hypothesize that host responses differ between
mono-infections and co-infections. We anticipate that upon completion of the studies we will have identified: (i)
differences in the transcriptional profiles of the pathogens and the host in co-infection compared with mono-
infection, (ii) genes that were not previously known to be involved in pathogenesis for these important
pathogens, and (iii) novel host pathways driving immune and other responses to co-infections. Overall, the
findings of this study will advance knowledge of the role of bacterial-bacterial and bacterial-viral co-pathogens
in lung infections a...

## Key facts

- **NIH application ID:** 10375509
- **Project number:** 5U19AI110820-09
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** David A Rasko
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $787,248
- **Award type:** 5
- **Project period:** 2014-04-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375509

## Citation

> US National Institutes of Health, RePORTER application 10375509, A Multi-Omics Approach to the Examination of Bacterial Co-pathogens (5U19AI110820-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10375509. Licensed CC0.

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