Transitory Shifts in Skin Microbiota Composition and Reductions in Bacterial Load and Psoriasin following Ethanol Perturbation.

Personal care and hygiene regimens may substantially alter the composition of the skin microbiota through direct and indirect mechanisms. An understanding of the timescales of commensal skin microbiota reestablishment following perturbation is required to inform consumer safety risk assessment, and support product development. In the current investigation, the microbiota of the volar and dorsal forearm of 10 volunteers was sampled immediately before and after wiping with 70% ethanol and at up to 24 h afterwards.

An Epidermal-Specific Role for Arginase1 during Cutaneous Wound Repair.

Nonhealing wounds are a major area of unmet clinical need remaining problematic to treat. Improved understanding of prohealing mechanisms is invaluable. The enzyme arginase1 (ARG1) is involved in prohealing responses, with its role in macrophages best characterized.

Staphylococcus aureus second immunoglobulin-binding protein drives atopic dermatitis via IL-33.

Background: Staphylococcus aureus is the dominant infective trigger of atopic dermatitis (AD). How this bacterium drives type 2 allergic pathology in the absence of infection in patients with AD is unclear.

Objective: We sought to identify the S aureus-derived virulence factor(s) that initiates the cutaneous type 2-promoting immune response responsible for AD.

Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo.

Mycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology.

Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair.

Efficient local monocyte/macrophage recruitment is critical for tissue repair. Recruited macrophages are polarized toward classical (proinflammatory) or alternative (prohealing) activation in response to cytokines, with tight temporal regulation crucial for efficient wound repair. Estrogen acts as a potent anti-inflammatory regulator of cutaneous healing.

Local arginase 1 activity is required for cutaneous wound healing.

Chronic nonhealing wounds in the elderly population are associated with a prolonged and excessive inflammatory response, which is widely hypothesized to impede healing. Previous studies have linked alterations in local L-arginine metabolism, principally mediated by the enzymes arginase (Arg) and inducible nitric oxide synthase (iNOS), to pathological wound healing. Over subsequent years, interest in Arg/iNOS has focused on the classical versus alternatively activated (M1/M2) macrophage paradigm.

A new family of phosphoinositide phosphatases in microorganisms: identification and biochemical analysis.

Background: Phosphoinositide metabolism is essential to membrane dynamics and impinges on many cellular processes, including phagocytosis. Modulation of phosphoinositide metabolism is important for pathogenicity and virulence of many human pathogens, allowing them to survive and replicate in the host cells. Phosphoinositide phosphatases from bacterial pathogens are therefore key players in this modulation and constitute attractive targets for chemotherapy.