Journal article
The impact of nutritional immunity on Group B streptococcal pathogenesis during wound infection
mBio, Vol.14(4), pp.e0030423-e0030423
08/31/2023
DOI: 10.1128/mbio.00304-23
PMCID: PMC10470527
PMID: 37358277
Abstract
Group B
(GBS) is a Gram-positive pathobiont that can cause adverse health outcomes in neonates and vulnerable adult populations. GBS is one of the most frequently isolated bacteria from diabetic (Db) wound infections but is rarely found in the non-diabetic (nDb) wound environment. Previously, RNA sequencing of wound tissue from Db wound infections in
diabetic mice showed increased expression of neutrophil factors, and genes involved in GBS metal transport such as the zinc (Zn), manganese (Mn), and putative nickel (Ni) import systems. Here, we develop a Streptozotocin-induced diabetic wound model to evaluate the pathogenesis of two invasive strains of GBS, serotypes Ia and V. We observe an increase in metal chelators such as calprotectin (CP) and lipocalin-2 during diabetic wound infections compared to nDb. We find that CP limits GBS survival in wounds of non-diabetic mice but does not impact survival in diabetic wounds. Additionally, we utilize GBS metal transporter mutants and determine that the Zn, Mn, and putative Ni transporters in GBS are dispensable in diabetic wound infection but contributed to bacterial persistence in non-diabetic animals. Collectively, these data suggest that in non-diabetic mice, functional nutritional immunity mediated by CP is effective at mitigating GBS infection, whereas in diabetic mice, the presence of CP is not sufficient to control GBS wound persistence. IMPORTANCE Diabetic wound infections are difficult to treat and often become chronic due to an impaired immune response as well as the presence of bacterial species that establish persistent infections. Group B
(GBS) is one of the most frequently isolated bacterial species in diabetic wound infections and, as a result, is one of the leading causes of death from skin and subcutaneous infection. However, GBS is notoriously absent in non-diabetic wounds, and little is known about why this species thrives in diabetic infection. The work herein investigates how alterations in diabetic host immunity may contribute to GBS success during diabetic wound infection.
Details
- Title: Subtitle
- The impact of nutritional immunity on Group B streptococcal pathogenesis during wound infection
- Creators
- Madeline S Akbari - University of Colorado Anschutz Medical CampusRebecca A Keogh - University of Colorado Anschutz Medical CampusJana N Radin - University of Illinois Urbana-ChampaignYamil Sanchez-Rosario - University of ArizonaMichael D L Johnson - University of ArizonaAlexander R Horswill - University of Colorado Anschutz Medical CampusThomas E Kehl-Fie - University of Illinois Urbana-ChampaignLindsey R Burcham - University of Colorado Anschutz Medical CampusKelly S Doran - University of Colorado Anschutz Medical Campus
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.14(4), pp.e0030423-e0030423
- DOI
- 10.1128/mbio.00304-23
- PMID
- 37358277
- PMCID
- PMC10470527
- ISSN
- 2161-2129
- eISSN
- 2150-7511
- Grant note
- F32 AI172126 / NIAID NIH HHS T32 GM139779 / NIGMS NIH HHS R35 GM128653 / NIGMS NIH HHS T32 GM136536 / NIGMS NIH HHS R21 AI159040 / NIAID NIH HHS R01 AI155611 / NIAID NIH HHS R01 AI153332 / NIAID NIH HHS
- Language
- English
- Date published
- 08/31/2023
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984618634802771
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