{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:21:18Z","timestamp":1780633278465,"version":"3.54.1"},"reference-count":63,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:p>Virtually all diabetes\u2010related foot ulcers (DRFUs) will become colonized by microorganisms that may increase the risk of developing an infection. The reasons why some ulcerations develop acute clinical infections (AI\u2010DRFUs) whilst others develop chronic infection (CI\u2010DRFUs) and the preceding host\u2010microbe interactions <jats:italic>in\u2009vivo<\/jats:italic> remain largely unknown. Establishing that acute and chronic infections are distinct processes requires demonstrating that these are two different strategies employed by microbes when interacting with a host. In this study, dual\u2010RNA seq was employed to differentiate the host\u2010microbe metatranscriptome between DRFUs that had localized chronic infection or acute clinical infection. Comparison of the host metatranscriptome in AI\u2010DRFUs relative to CI\u2010DRFUs identified upregulated differentially expressed genes (DEGs) that functioned as regulators of vascular lymphatic inflammatory responses, T\u2010cell signalling and olfactory receptors. Conversely, CI\u2010DRFUs upregulated DEGs responsible for cellular homeostasis. Gene set enrichment analysis using Hallmark annotations revealed enrichment of immune and inflammatory profiles in CI\u2010DRFUs relative to AI\u2010DRFUs. Analysis of the microbial metatranscriptome identified the DEGs being enriched within AI\u2010DRFUs relative to CI\u2010DRFUs included several toxins, two\u2010component systems, bacterial motility, secretion systems and genes encoding for energy metabolism. Functions relevant to DRFU pathology were further explored, including biofilm and bacterial pathogenesis. This identified that the expression of biofilm\u2010associated genes was higher within CI\u2010DRFUs compared to that of AI\u2010DRFUs, with mucR being the most highly expressed gene. Collectively, these data provide insights into the host\u2010microbe function in two clinically\u2010distinct infective phenotypes that affect DRFUs. The data reveal that bacteria in acutely infected DRFUs prioritize motility over biofilm and demonstrate greater pathogenicity and mechanisms, which likely subvert host cellular and immune pathways to establish infection. Upregulation of genes for key vascular inflammatory mediators in acutely infected ulcers may contribute, in part, to the clinical picture of a red, hot, swollen foot, which differentiates an acutely infected ulcer from that of a chronic infection.<\/jats:p>","DOI":"10.1111\/apm.13200","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T07:14:22Z","timestamp":1639120462000},"page":"751-762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Host\u2010microbe metatranscriptome reveals differences between acute and chronic infections in diabetes\u2010related foot ulcers"],"prefix":"10.1111","volume":"130","author":[{"given":"Matthew","family":"Malone","sequence":"first","affiliation":[{"name":"South West Sydney Limb Preservation and Wound Research South Western Sydney LHD  Sydney NSW Australia"},{"name":"Infectious Diseases and Microbiology School of Medicine Western Sydney University 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