Activates Quorum Sensing, Antioxidant Enzymes and Type VI Secretion in Response to Oxidative Stress to Initiate Biofilm Formation and Wound Chronicity.

() is an opportunistic pathogen frequently isolated from cutaneous chronic wounds. How , in the presence of oxidative stress (OS), colonizes chronic wounds and forms a biofilm is still unknown. The purpose of this study is to investigate the changes in gene expression seen when PA is challenged with the high levels of OS present in chronic wounds.

Targeting Anaerobic Respiration in with Chlorate Improves Healing of Chronic Wounds.

is an opportunistic pathogen that can establish chronic infections and form biofilm in wounds. Because the wound environment is largely devoid of oxygen, may rely on anaerobic metabolism, such as nitrate respiration, to survive in wounds. While nitrate reductase (Nar) typically reduces nitrate to nitrite, it can also reduce chlorate to chlorite, which is a toxic oxidizing agent.

Using systems biology approaches to identify signalling pathways activated during chronic wound initiation.

Chronic wounds are a significant health problem worldwide. However, nothing is known about how chronic wounds initiate and develop. Here we use a chronic wound model in diabetic mice and a Systems Biology Approach using nanoString nCounter technology and weighted gene correlation network analysis (WGCNA), with tissues collected at 6, 12, 24 and 48 h post-wounding, to identify metabolic signalling pathways involved in initiation of chronicity.

A Bayesian longitudinal trend analysis of count data with Gaussian processes.

The context of comparing two different groups of subjects that are measured repeatedly over time is considered. Our specific focus is on highly variable count data which have a nonnegligible frequency of zeros and have time trends that are difficult to characterize. These challenges are often present when analyzing bacteria or gene expression data sets.

Herpes simplex virus infection, Acyclovir and IVIG treatment all independently cause gut dysbiosis.

Herpes simplex virus 1 (HSV) is a ubiquitous human virus resident in a majority of the global population as a latent infection. Acyclovir (ACV), is the standard of care drug used to treat primary and recurrent infections, supplemented in some patients with intravenous immunoglobulin (IVIG) treatment to suppress infection and deleterious inflammatory responses. As many diverse medications have recently been shown to change composition of the gut microbiome, we used Illumina 16S rRNA gene sequencing to determine the effects of ACV and IVIG on the gut bacterial community.

High Levels of Oxidative Stress Create a Microenvironment That Significantly Decreases the Diversity of the Microbiota in Diabetic Chronic Wounds and Promotes Biofilm Formation.

Diabetics chronic wounds are characterized by high levels of oxidative stress (OS) and are often colonized by biofilm-forming bacteria that severely compromise healing and can result in amputation. However, little is known about the role of skin microbiota in wound healing and chronic wound development. that high OS levels lead to chronic wound development by promoting the colonization of biofilm-forming bacteria over commensal/beneficial bacteria.

High Levels of Oxidative Stress and Skin Microbiome are Critical for Initiation and Development of Chronic Wounds in Diabetic Mice.

A balanced redox state is critical for proper healing. Although human chronic wounds are characterized by high levels of oxidative stress (OS), whether OS levels are critical for chronic wound development is not known. For these studies, we used our chronic wound model in diabetic mice that has similar characteristics as human chronic wounds, including naturally developed biofilm.

Protocol to Create Chronic Wounds in Diabetic Mice.

Chronic wounds develop as a result of defective regulation in one or more complex cellular and molecular processes involved in proper healing. They impact ~6.5M people and cost ~$40B/year in the US alone.

WT1-interacting protein (Wtip) regulates podocyte phenotype by cell-cell and cell-matrix contact reorganization.

Podocytes respond to environmental cues by remodeling their slit diaphragms and cell-matrix adhesive junctions. Wt1-interacting protein (Wtip), an Ajuba family LIM domain scaffold protein expressed in the podocyte, coordinates cell adhesion changes and transcriptional responses to regulate podocyte phenotypic plasticity. We evaluated effects of Wtip on podocyte cell-cell and cell-matrix contact organization using gain-of- and loss-of-function methods.

Mesangial cell integrin αvβ8 provides glomerular endothelial cell cytoprotection by sequestering TGF-β and regulating PECAM-1.

Integrins are heterodimeric receptors that regulate cell adhesion, migration, and apoptosis. Integrin αvβ8 is most abundantly expressed in kidney and brain, and its major ligand is latent transforming growth factor-β (TGF-β). Kidney αvβ8 localizes to mesangial cells, which appose glomerular endothelial cells and maintain glomerular capillary structure by mechanical and poorly understood paracrine mechanisms.

Podocyte injury induces nuclear translocation of WTIP via microtubule-dependent transport.

Podocyte structural and transcriptional phenotype plasticity characterizes glomerular injury. Transcriptional activity of WT1 (Wilm's tumor 1) is required for normal podocyte structure and is repressed by the podocyte adherens junction protein, WTIP (WT1 interacting protein). Here we show that WTIP translocated into podocyte nuclei in lipopolysaccharide (LPS)-treated mice, a model of transient nephrotic syndrome.

Out on a LIM: chronic kidney disease, podocyte phenotype and the Wilm's tumor interacting protein (WTIP).

Normal function of the glomerular filtration barrier requires wild-type differentiation of the highly specialized glomerular epithelial cell, the podocyte. Podocytes express three distinct domains, consisting of a cell body, primary processes, and secondary foot processes (FP). These FP express slit diaphragms, which are highly specialized cell-cell contacts critical for filtration-barrier function.