# Host-pathogen interactions during GBS diabetic wound infections

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2024 · $37,658

## Abstract

PROJECT SUMMARY
Group B Streptococcus (GBS), is a Gram-positive pathobiont that commonly colonizes the gastrointestinal and
lower female reproductive tracts but can cause adverse health outcomes in neonates and vulnerable adult
populations. GBS has also been increasingly associated with diabetic wound infections and is the third leading
cause of death from skin and subcutaneous infection. It is estimated that over 500 million people have diabetes
today with one of the most common complications being chronic wounds that fail to heal due to other diabetic
complications and their high susceptibility to bacterial infection. Our lab recently performed dual RNA-sequencing
on GBS infected wound tissues from diabetic mice (Db). Results showed significant increased transcription of
many known GBS metal transport systems in Db wounds compared to culture controls including zinc
(adcABC,adcAII,lmb), manganese (mtsABC), and an unknown metal transport system (nikABCDE). Preliminary
results show that the putative GBS Nik transporter has high protein similarity and structure to the known E. coli
nickel ABC-type transporter and is turned on under metal stress indicating it may play a role in GBS metal
homeostasis. We also observed significant increased transcription and concentration of host calprotectin (CP),
a neutrophil-derived metal chelator, in infected Db wounds compared to uninfected controls. Metal transport
systems are key players in maintaining metal homeostasis of divalent cations, nutrients that are needed for all
living organisms, while CP is a hallmark of inflammation and is involved in nutritional immunity where the host
starves invading pathogens of nutrients necessary for survival. The role of the putative nickel transport system,
NikABCDE, in GBS and during Db wound infection is unknown. Neutrophils also make a toxic byproduct of
glycolysis called methylglyoxal (MGX) that can be broken down by a two-step pathway catalyzed by glyoxalase
A and B. MGX is also increased in Db individuals and is a precursor to advanced glycation end products (AGEs)
which further exacerbate Db complications. GBS contains homologous glyoxalase enzymes and preliminary data
shows glyoxalase A contributes to GBS growth in the presence of MGX. This proposal seeks to characterize the
putative nickel transporter in GBS and investigate the role of GBS MGX detoxification during Db wound infection.
I hypothesize that the putative nickel transporter and MGX detoxification pathway are important for overcoming
metal and MGX stress during infection. These hypotheses will be addressed with both in vitro biophysical and
growth assays and in vivo models of Db wound infection in the following specific aims: (1) characterize the
putative metal ATP binding cassette (ABC) transporter, NikABCDE, and (2) characterize the putative MGX
detoxification system in GBS and its role during diabetic wound infection.

## Key facts

- **NIH application ID:** 10895767
- **Project number:** 1F31AI178881-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Madeline Sohayla Akbari
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $37,658
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895767

## Citation

> US National Institutes of Health, RePORTER application 10895767, Host-pathogen interactions during GBS diabetic wound infections (1F31AI178881-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10895767. Licensed CC0.

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