Propionibacterium acnes bacteriophages display limited genetic diversity and broad killing activity against bacterial skin isolates.

UnlabelledInvestigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne.ImportancePropionibacterium acnes is a dominant member of the skin microflora and has also been implicated in the pathogenesis of acne; however, little is known about the bacteriophages that coexist with and infect this bacterium. Here we present the novel genome sequences of 11 P. acnes phages, thereby substantially increasing the amount of available genomic information about this phage population. Surprisingly, we find that, unlike other well-studied bacteriophages, P. acnes phages are highly homogeneous and show a striking lack of genetic diversity, which is perhaps related to their unique and restricted habitat. They also share a broad ability to kill clinical isolates of P. acnes; phage resistance is not prevalent, but when detected, it appears to be conferred by chromosomally encoded immunity elements within the host genome. We believe that these phages display numerous features that would make them ideal candidates for the development of a phage-based therapy for acne

Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials

The exquisite structure-function correlations observed in filamentous protein assemblies provide a paradigm for the design of synthetic peptide-based nanomaterials. However, the plasticity of quaternary structure in sequence-space and the lability of helical symmetry present significant challenges to the de novo design and structural analysis of such filaments. Here, we describe a rational approach to design self-assembling peptide nanotubes based on controlling lateral interactions between protofilaments having an unusual cross-α supramolecular architecture. Near-atomic resolution cryo-EM structural analysis of seven designed nanotubes provides insight into the designability of interfaces within these synthetic peptide assemblies and identifies a non-native structural interaction based on a pair of arginine residues. This arginine clasp motif can robustly mediate cohesive interactions between protofilaments within the cross-α nanotubes. The structure of the resultant assemblies can be controlled through the sequence and length of the peptide subunits, which generates synthetic peptide filaments of similar dimensions to flagella and pili

Self-rated health and health care access associated with African American men’s health self-efficacy

Health self-efficacy, a measure of one’s self-assurance in taking care of their own health, is known to contribute to a range of health outcomes that has been under examined among African American men. The purpose of this investigation was to identify and contextualize predictors of general health self-efficacy in this population. A cross-sectional sample of surveys from 558 African American was examined. These men were older than 18 years, could read and write English, and attended a hospital-based community health fair targeting minority men in 2011. The outcome of interest was health self-efficacy, which was assessed by asking, “Overall, how confident are you in your ability to take good care of your health?” Responses ranged from 1 (not confident at all) to 5 (completely confident). Covariates included age, self-rated health, health insurance status, having a regular physician, and being a smoker. The mean age of participants was 54.4 years, and 61.3% of participants indicated confidence in their ability to take good care of their health. Older age and being a smoker were inversely associated with the outcome. Good self-rated health, having health insurance, and having a regular doctor were positively associated with reports of health self-efficacy. Findings suggest that multiple points of connection to the health care system increase the likelihood of health self-efficacy for this sample and interventions to support older African American men who may evaluate their own health status as poor and who may face barriers to health care access are implicated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/164711/1/Thompson et al 2017 Self-rated health and health care access.pdfDescription of Thompson et al 2017 Self-rated health and health care access.pdf : Main articl

Complete genomic sequences of Propionibacterium freudenreichii phages from Swiss cheese reveal greater diversity than Cutibacterium (formerly Propionibacterium) acnes phages

Background:A remarkable exception to the large genetic diversity often observed for bacteriophages infecting aspecific bacterial host was found for the Cutibacterium acnes (formerly Propionibacterium acnes) phages, which are highly homogeneous. Phages infecting the related species, which is also a member of the Propionibacteriaceae family, Propionibacterium freudenreichii , a bacterium used in production of Swiss-type cheeses, have also been described and are common contaminants of the cheese manufacturing process. However, little is known about their genetic composition and diversity.Results:We obtained seven independently isolated bacteriophages that infect P. freudenreichii from Swiss-typecheese samples, and determined their complete genome sequences. These data revealed that all seven phage isolates are of similar genomic length and GC% content, but their genomes are highly diverse, including genes encoding the capsid, tape measure, and tail proteins. In contrast to C. acnes phages, all P. freudenreichii phage genomes encode a putative integrase protein, suggesting they are capable of lysogenic growth. This is supported by the finding of related prophages in some P. freudenreichii strains. The seven phages could further be distinguished as belonging to two distinct genomic types, or ‘ clusters ’ , based on nucleotide sequences, and host range analyses conducted on a collection of P. freudenreichii strains show a higher degree of host specificity than is observed for the C. acnes phages.Conclusions:Overall, our data demonstrate P. freudenreichii bacteriophages are distinct from C. acnes phages, asevidenced by their higher genetic diversity, potential for lysogenic growth, and more restricted host ranges. This suggests substantial differences in the evolution of these related species from the Propionibacteriaceae family and their phages, which is potentially related to their distinct environmental niches

Local Suppression of T Cell Responses by Arginase-Induced L-Arginine Depletion in Nonhealing Leishmaniasis

The balance between T helper (Th) 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of pathology. The high arginase activity causes local depletion of L-arginine, which impairs the capacity of T cells in the lesion to proliferate and to produce interferon-γ, while T cells in the local draining lymph nodes respond normally. Healing, induced by chemotherapy, resulted in control of arginase activity and reversal of local immunosuppression. Moreover, competitive inhibition of arginase as well as supplementation with L-arginine restored T cell effector functions and reduced pathology and parasite growth at the site of lesions. These results demonstrate that in nonhealing leishmaniasis, arginase-induced L-arginine depletion results in impaired T cell responses. Our results identify a novel mechanism in leishmaniasis that contributes to the failure to heal persistent lesions and suggest new approaches to therapy

Social determinants associated with colorectal cancer screening among an urban sample of African American men

http://deepblue.lib.umich.edu/bitstream/2027.42/117268/1/24. Mitchell Watkins & Modlin 2013.pdfDescription of 24. Mitchell Watkins & Modlin 2013.pdf : Main articl

Disparities in health-related Internet use among African American men, 2010

Brief.Given the benefits of health-related Internet use, we examined whether sociodemographic, medical, and access-related factors predicted this outcome among African American men, a population burdened with health disparities. African American men (n = 329) completed an anonymous survey at a community health fair in 2010; logistic regression was used to identify predictors. Only education (having attended some college or more) predicted health-related Internet use (P < .001). African American men may vary in how they prefer to receive health information; those with less education may need support to engage effectively with health-related Internet use.National Institute on Aging, National Institutes of Health (5P30 AG015281)Centers for Medicare and Medicaid Services (1 AO CMS 3000068)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171270/1/Mitchell Thompson Watkins Disparities in health- related Internet use among African American men 2010.pd

Structurally Ordered Nanowire Formation from Co-Assembly of DNA Origami and Collagen-Mimetic Peptides

We describe the co-assembly of two different building units: collagen-mimetic peptides and DNA origami. Two peptides <b>CP</b>^<b>++</b> and <b>sCP</b>^<b>++</b> are designed with a sequence comprising a central block (Pro-Hyp-Gly) and two positively charged domains (Pro-Arg-Gly) at both N- and C-termini. Co-assembly of peptides and DNA origami two-layer (<b>TL</b>) nanosheets affords the formation of one-dimensional nanowires with repeating periodicity of ∼10 nm. Structural analyses suggest a face-to-face stacking of DNA nanosheets with peptides aligned perpendicularly to the sheet surfaces. We demonstrate the potential of selective peptide-DNA association between face-to-face and edge-to-edge packing by tailoring the size of DNA nanostructures. This study presents an attractive strategy to create hybrid biomolecular assemblies from peptide- and DNA-based building blocks that takes advantage of the intrinsic chemical and physical properties of the respective components to encode structural and, potentially, functional complexity within readily accessible biomimetic materials