The impact of nutritional immunity on Group B streptococcal pathogenesis during wound infection

Madeline S. Akbari, Rebecca A. Keogh, Jana N. Radin, Yamil Sanchez-Rosario, Michael D.L. Johnson, Alexander R. Horswill, Thomas E. Kehl-Fie, Lindsey R. Burcham, Kelly S. Doran

Research output: Contribution to journalArticlepeer-review

Abstract

Group B Streptococcus (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 leprdb 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 findthat 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 effectiveat mitigating GBS infection, whereas in diabetic mice, the presence of CP is not sufficientto control GBS wound persistence.

Original languageEnglish (US)
JournalmBio
Volume14
Issue number4
DOIs
StatePublished - Jul 2023

Keywords

  • ABC transporters
  • Group B streptococcus
  • diabetes
  • innate immunity
  • neutrophils
  • soft tissue infection

ASJC Scopus subject areas

  • Microbiology
  • Virology

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