Loss of GdpP Function in Staphylococcus aureus Leads to β-Lactam Tolerance and Enhanced Evolution of β-Lactam Resistance.

Infections caused by Staphylococcus aureus are a leading cause of mortality. Treating infections caused by S. aureus is difficult due to resistance against most traditional antibiotics, including β-lactams.

Frontline Science: Breast milk confers passive cellular immunity via CD8-dependent mechanisms.

Most modern research into the immune effects of breast milk has focused on the impacts of immunoglobulin or oligosaccharide content. However, immediately prior to parturition, the cell populations of breast milk become selectively enriched for CD8+ T cells of an effector memory subtype. Despite this observation that the cellular content of breast milk contains a distinct leukocyte population when compared to peripheral blood, the physiologic role of these CD8+ effector memory cells is unknown.

Political competition and public healthcare expenditure: Evidence from Indian states.

In-spite of being the largest democracy in the world, Indian states are spending only around 1% of net state domestic product on public healthcare which is way lower than the world average. This low level of public healthcare spending resulted in a high out of pocket healthcare spending and poor health outcome in India. But democratically elected governments are responsible for spending significant amount of their budget on healthcare for the benefit of the masses.

Differing Virulence of Healthy Skin Commensals in Mouse Models of Infection.

As therapies for atopic dermatitis (AD) based on live biotherapeutic products (LBP) are developed, the potential displacement of biotherapeutic strains, and species to mucosal sites where they are not naturally found is of investigative interest. However, formal assessment of the toxicity potential of healthy skin commensal organisms has not been reported in the literature. Our previous research indicates that topical application of live to treat AD was associated with clinical benefit on the skin, but the effects of exposure via inhalation, eye inoculation, and ingestion were unknown.

Prolonging culture of primary human keratinocytes isolated from suction blisters with the Rho kinase inhibitor Y-27632.

Keratinocytes are the most abundant cell type in the epidermis. They prevent desiccation and provide immunological and barrier defense against potential pathogens such as Staphylococcus aureus and Candida albicans. The study of this first line of immune defense may be hindered by invasive isolation methods and/or improper culture conditions to support stem cell maintenance and other potential mechanisms contributing to long-term subcultivation in vitro.

Vaccine display on artificial bacterial spores enhances protective efficacy against Staphylococcus aureus infection.

Spores of Bacillus subtilis are encased in a protein coat composed of ∼80 different proteins. Recently, we reconstituted the basement layer of the coat, composed of two structural proteins (SpoVM and SpoIVA) around spore-sized silica beads encased in a lipid bilayer, to create synthetic spore-like particles termed 'SSHELs'. We demonstrated that SSHELs could display thousands of copies of proteins and small molecules of interest covalently linked to SpoIVA.

TNF overproduction impairs epithelial staphylococcal response in hyper IgE syndrome.

Autosomal dominant hyper IgE syndrome (AD-HIES), or Job's syndrome, is a primary immune deficiency caused by dominant-negative mutations in STAT3. Recurrent Staphylococcus aureus skin abscesses are a defining feature of this syndrome. A widely held hypothesis that defects in peripheral Th17 differentiation confer this susceptibility has never been directly evaluated.

Using community health workers to refer pregnant women and young children to health care facilities in rural West Bengal, India: A prospective cohort study.

Background: Community health workers (CHWs) have been placed in many rural areas in India to increase villagers' connections to basic preventive health care. In this study, we describe how pregnant women and mothers of young children react when CHWs inform them that they, or their child, are at high risk of pregnancy-related complications or early childhood developmental delays, and further screening and health care from a physician is recommended.

Methods: In this longitudinal study in rural villages in West Bengal, India, pregnant mothers, as well as mothers of children aged 12-24 months, were screened for high risk complications.

First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis.

The underlying pathology of atopic dermatitis (AD) includes impaired skin barrier function, susceptibility to Staphylococcus aureus skin infection, immune dysregulation, and cutaneous dysbiosis. Our recent investigation into the potential role of Gram-negative skin bacteria in AD revealed that isolates of one particular commensal, Roseomonas mucosa, collected from healthy volunteers (HVs) improved outcomes in mouse and cell culture models of AD. In contrast, isolates of R.

Risk Factors During Pregnancy and Early Childhood in Rural West Bengal, India: A Feasibility Study Implemented via Trained Community Health Workers Using Mobile Data Collection Devices.

Objectives This study measures the prevalence of risk factors among pregnant women and young children aged 12-24 months in a rural community in West Bengal, India. Methods Community health workers (CHWs) enrolled women and children into this 2015 cross-sectional study. Pregnant women were evaluated for underweight, anemia, and abnormal blood pressure.

STAT-3-independent production of IL-17 by mouse innate-like αβ T cells controls ocular infection.

Appropriate regulation of IL-17 production in the host can mean the difference between effective control of pathogens and uncontrolled inflammation that causes tissue damage. Investigation of conventional CD4 T cells (Th17 cells) has yielded invaluable insights into IL-17 function and its regulation. More recently, we and others reported production of IL-17 from innate αβ+ T cell populations, which was shown to occur primarily via IL-23R signaling through the transcription factor STAT-3.

Influence of multiplicative stochastic variation on translational elongation rates.

Experimental data indicate that stochastic effects exerted at the level of translation contribute substantially to the variation in abundance of proteins expressed at moderate to high levels. This study analyzes the theoretical consequences of fluctuations in residue-specific elongation rates during translation. A simple analytical framework shows that rate variation during elongation gives rise to protein production rates that consist of sums of products of random variables.

CD8 T cell dialyzable extract activity is dependent on TCR and MHC-I.

Author response.

PBP4 Mediates β-Lactam Resistance by Altered Function.

Penicillin binding protein 4 (PBP4) can provide high-level β-lactam resistance in A series of missense and promoter mutations associated with were detected in strains that displayed high-level resistance. We show here that the missense mutations facilitate the β-lactam resistance mediated by PBP4 and the promoter mutations lead to overexpression of Our results also suggest a cooperative interplay among PBPs for β-lactam resistance.

IL-22: Scavenging beyond the barrier.

IL-22-induced hemopexin promotes nutritional immunity by scavenging iron from during systemic infection.

Molecular Typing of Staphylococcus aureus Isolated from Patients with Autosomal Dominant Hyper IgE Syndrome.

Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by a loss-of-function mutation in the Signal Transducer and Activator of Transcription 3 (STAT3). This immune disorder is clinically characterized by increased susceptibility to cutaneous and sinopulmonary infections, in particular with and . It has recently been recognized that the skin microbiome of patients with AD-HIES is altered with an overrepresentation of certain Gram-negative bacteria and Gram-positive staphylococci.

IL-20 Signaling in Activated Human Neutrophils Inhibits Neutrophil Migration and Function.

Neutrophils possess multiple antimicrobial mechanisms that are critical for protection of the host against infection with extracellular microbes, such as the bacterial pathogen Recruitment and activation of neutrophils at sites of infection are driven by cytokine and chemokine signals that directly target neutrophils via specific cell surface receptors. The IL-20 subfamily of cytokines has been reported to act at epithelial sites and contribute to psoriasis, wound healing, and anti-inflammatory effects during infection. However, the ability of these cytokines to directly affect neutrophil function remains incompletely understood.

Lethal CD4 T Cell Responses Induced by Vaccination Against Staphylococcus aureus Bacteremia.

Multiple candidate vaccines against Staphylococcus aureus infections have failed in clinical trials. Analysis of a recent prematurely halted vaccine trial revealed increased mortality rates among vaccine recipients in whom postsurgical S. aureus infection developed, emphasizing the potential for induction of detrimental immune responses and the need to better understand the requirements for protective immunity against S.

CD8+ T cells produce a dialyzable antigen-specific activator of dendritic cells.

Cellular lysates from PPD donors have been reported to transfer tuberculin reactivity to naïve recipients, but not diphtheria reactivity, and vice versa. A historically controversial topic, the terms "transfer factor" and "DLE" were used to characterize the reactivity-transferring properties of lysates. Intrigued by these reported phenomena, we found that the cellular extract derived from antigen-specific memory CD8 T cells induces IL-6 from antigen-matched APCs.

Transplantation of human skin microbiota in models of atopic dermatitis.

Atopic dermatitis (AD) is characterized by reduced barrier function, reduced innate immune activation, and susceptibility to . Host susceptibility factors are suggested by monogenic disorders associated with AD-like phenotypes and can be medically modulated. contributes to AD pathogenesis and can be mitigated by antibiotics and bleach baths.

A method for culturing Gram-negative skin microbiota.

Background: Commensal Gram-negative (CGN) microbiota have been identified on human skin by DNA sequencing; however, methods to reliably culture viable Gram-negative skin organisms have not been previously described.

Results: Through the use of selective antibiotics and minimal media we developed methods to culture CGN from skin swabs. We identified several previously uncharacterized CGN at the species level by optimizing growth conditions and limiting the inhibitory effects of nutrient shock, temperature, and bacterial competition, factors that may have previously limited CGN isolation from skin cultures.

Adaptive Immunity Against Staphylococcus aureus.

A complex interplay between host and bacterial factors allows Staphylococcus aureus to occupy its niche as a human commensal and a major human pathogen. The role of neutrophils as a critical component of the innate immune response against S. aureus, particularly for control of systemic infection, has been established in both animal models and in humans with acquired and congenital neutrophil dysfunction.

CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion of the Central Nervous System.

Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear.

Antibiotic Education: Not Just Another Brick in the Cell Wall.

Methicillin-resistant Staphylococcus aureus (MRSA) are resistant to β-lactam antibiotics, which inhibit bacterial cell wall synthesis. In this issue of Cell Host & Microbe, Müller et al. (2015) show that β-lactam treatment of MRSA leads to synthesis of an altered cell wall that increases inflammasome activation and immunopathology during skin infection.