Strain- and Species-Level Variation in the Microbiome of Diabetic Wounds Is Associated with Clinical Outcomes and Therapeutic Efficacy

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2019 Apr 23

PMID 31006638

Citations 133

Authors

Lindsay R Kalan

Jacquelyn S Meisel

Michael A Loesche

Joseph Horwinski

Ioana Soaita

Xiaoxuan Chen

Aayushi Uberoi

Sue E Gardner

Elizabeth A Grice

Affiliations

Soon will be listed here.

Abstract

Chronic wounds are a major complication of diabetes associated with high morbidity and health care expenditures. To investigate the role of colonizing microbiota in diabetic wound healing, clinical outcomes, and response to interventions, we conducted a longitudinal, prospective study of patients with neuropathic diabetic foot ulcers (DFU). Metagenomic shotgun sequencing revealed that strain-level variation of Staphylococcus aureus and genetic signatures of biofilm formation were associated with poor outcomes. Cultured wound isolates of S. aureus elicited differential phenotypes in mouse models that corresponded with patient outcomes, while wound "bystanders" such as Corynebacterium striatum and Alcaligenes faecalis, typically considered commensals or contaminants, also significantly impacted wound severity and healing. Antibiotic resistance genes were widespread, and debridement, rather than antibiotic treatment, significantly shifted the DFU microbiota in patients with more favorable outcomes. These findings suggest that the DFU microbiota may be a marker for clinical outcomes and response to therapeutic interventions.

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