Publications by authors named "Lindsay Kalan"

Article Synopsis
  • The human skin microbiome acts as a protective barrier against pathogens by producing antimicrobial substances, making it a valuable resource for discovering new natural products.
  • Researchers introduced the EPithelial Isolate Collection (EPIC), which comprises 980 diverse bacterial strains from human skin across eight body sites, including many rare strains with unique biosynthetic gene clusters (BGCs).
  • Through extensive testing, they found that this microbiome exhibits strong antifungal properties, with certain body sites showing higher potential for discovering new bioactive compounds, leading to advancements in antimicrobial drug development and microbiome research.
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Background: Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. The role of the nasal and oral microbiome in the context of early life respiratory infections and subsequent allergic disease risk remains understudied.

Objectives: Our aim was to gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics within the upper respiratory tract during infancy.

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Prenatal and early life farm exposure, and breastfeeding, are associated with protection from allergic diseases. We hypothesize that farm exposure influences the human breast milk microbiome and immune proteins. The immune protein profiles and microbial communities of 152 human breast milk samples were compared among three maternal farm exposure groups (traditional agrarian, farm, and non-farm) in rural Wisconsin to identify signatures associated with farm status and atopic disease.

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Background: Alterations in upper respiratory microbiomes have been implicated in shaping host health trajectories, including by limiting mucosal pathogen colonization. However, limited comparative studies of respiratory microbiome development and functioning across age groups have been performed. Herein, we perform shotgun metagenomic sequencing paired with pathogen inhibition assays to elucidate differences in nasal and oral microbiome composition and intermicrobial interactions across healthy 24-month-old infant (n = 229) and adult (n = 100) populations.

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The oral microbiome has been understudied as a reservoir for clinical pathogens, including drug-resistant strains. Understanding how alterations in microbiome functioning render this site vulnerable to colonization is essential, as multidrug-resistant organisms (MDRO) carriage is a major risk factor for developing serious infections. To advance our knowledge of oral MDRO carriage and protection against pathogen colonization conferred by native microbiota, we examined microbiomes from individuals colonized by MDROs (n=33) and non-colonized age-matched controls (n=30).

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Purpose Of Review: In 2019, the International Working Group on the Diabetic Foot voiced six concerns regarding the use of molecular microbiology techniques for routine diagnosis of infection complicating diabetic foot ulcers. The purpose of this review is to evaluate contemporary evidence addressing each of these concerns and describe promising avenues for continued development of molecular microbiology assays.

Recent Findings: Since 2019, the feasibility of conducting metagenomic and metatranscriptomic studies on diabetic foot ulcer samples has been shown.

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The skin and its microbiome function to protect the host from pathogen colonization and environmental stressors. In this study, using the Wisconsin Miniature Swine™ model, we characterize the porcine skin fungal and bacterial microbiomes, identify bacterial isolates displaying antifungal activity, and use whole-genome sequencing to identify biosynthetic gene clusters encoding for secondary metabolites that may be responsible for the antagonistic effects on fungi. Through this comprehensive approach of paired microbiome sequencing with culturomics, we report the discovery of novel species of Corynebacterium and Rothia.

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Article Synopsis
  • The study investigates the skin microbiome in pediatric patients with mild atopic dermatitis (AD), comparing it to age- and sex-matched controls while focusing on bacterial strains and metagenomic differences.
  • Significant changes were found in the composition of bacteria, particularly Staphylococci, between the AD and control groups, with specific strains exhibiting distinct toxin production.
  • The findings suggest that these strain-level variations in toxins may impact human keratinocyte function and could be relevant to the development and management of atopic dermatitis.
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Porcine models are frequently used for burn healing studies; however, factors including anatomic location and lack of standardised wound methods can impact the interpretation of wound data. The objectives of this study are to examine the influence of anatomical locations on the uniformity of burn creation and healing in porcine burn models. To optimise burn parameters on dorsal and ventral surfaces, ex vivo and in situ euthanized animals were first used to examine the location-dependence of the burn depth and contact time relationship.

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Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model.

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Background: Alterations in upper respiratory microbiomes have been implicated in shaping host health trajectories, including by limiting mucosal pathogen colonization. However, limited comparative studies of respiratory microbiome development and functioning across age groups have been performed. Herein, we perform shotgun metagenomic sequencing paired with pathogen inhibition assays to elucidate differences in nasal and oral microbiome composition and functioning across healthy 24-month-old infant (n=229) and adult (n=100) populations.

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Article Synopsis
  • This pilot study investigates the characteristics of slough in non-healing wounds, examining the protein and microbial components to understand how they relate to wound healing outcomes.* -
  • Ten participants with various types of slow-healing wounds were analyzed, revealing that slough is complex and varies in structure while being influenced by the wound's location and type.* -
  • The research integrated clinical, microbiological, and proteomic data to identify potential biomarkers for poor healing, suggesting that certain proteins and bacteria can help predict wound recovery or deterioration.*
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Investigations of the bacterial family have enabled the development of secondary metabolites critical to human health. Historical investigation of bacterial families for natural product discovery has focused on terrestrial strains, where time-consuming isolation processes often lead to the rediscovery of known compounds. To investigate the secondary metabolite potential of marine-derived , 38 strains were sequenced, assembled and analysed using antiSMASH and BiG-SLiCE.

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skDER (https://github.com/raufs/skDER) combines recent advances to efficiently estimate average nucleotide identity (ANI) between thousands of microbial genomes by skani with two low-memory methods for genomic dereplication. The first method implements a dynamic algorithm to determine a concise set of representative genomes.

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Many universally and conditionally important genes are genomically aggregated within clusters. Here, we introduce fai and zol, which together enable large-scale comparative analysis of different types of gene clusters and mobile-genetic elements (MGEs), such as biosynthetic gene clusters (BGCs) or viruses. Fundamentally, they overcome a current bottleneck to reliably perform comprehensive orthology inference at large scale across broad taxonomic contexts and thousands of genomes.

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Bacterial secondary metabolites, synthesized by enzymes encoded in biosynthetic gene clusters (BGCs), can underlie microbiome homeostasis and serve as commercialized products, which have historically been mined from a select group of taxa. While evolutionary approaches have proven beneficial for prioritizing BGCs for experimental characterization efforts to uncover new natural products, dedicated bioinformatics tools designed for comparative and evolutionary analysis of BGCs within focal taxa are limited. We thus developed ineage pecific nalysis of BGCs (BGC; https://github.

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Wound cleansing agents are routine in wound care and preoperative preparation. Antiseptic activity intends to prevent contaminating microbes from establishing an infection while also raising concerns of cytotoxicity and delayed wound healing. We evaluated the cytotoxicity of five clinically used wound cleaning agents (saline, povidone iodine, Dove® and Dial® soaps, and chlorhexidine gluconate [CHG]) using both an ex vivo and in vivo human skin xenograft mouse model, in contrast to classical in vitro models that lack the structural and compositional heterogeneity of human skin.

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For decades research has centered on identifying the ideal balanced skin microbiome that prevents disease and on developing therapeutics to foster this balance. However, this single idealized balance may not exist. The skin microbiome changes across the lifespan.

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The microorganisms inhabiting human skin must overcome numerous challenges that typically impede microbial growth, including low pH, osmotic pressure, and low nutrient availability. Yet the skin microbiota thrive on the skin and have adapted to these stressful conditions. The limited nutrients available for microbial use in this unique niche include those from host-derived sweat, sebum, and corneocytes.

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are a diverse genus and dominant member of the human skin microbiome. Recently, we reported that the most prevalent species found on skin, including Corynebacterium tuberculostearicum and , comprise a narrow species complex despite the diversity of the genus. Here, we apply high-resolution phylogenomics and comparative genomics to describe the structure of the species complex and highlight genetic traits which are enriched or depleted in it relative to other .

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Wound infection is a major challenge for clinicians globally, with accurate and timely identification of wound infection being critical to achieving clinical and cost-effective management, and promotion of healing. This paper presents an overview of the development of the International Wound Infection Institute (IWII)'s 2022 Wound Infection in Clinical Practice consensus document. The updated document summarises current evidence and provides multidisciplinary healthcare providers with effective guidance and support on terminology, paradigms related to biofilm, identification of wound infection, wound cleansing, debridement and antimicrobial stewardship.

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The mosaic ecosystems of microbes that live on our skin encompass not only bacteria but also fungi, microeukaryotes, and viruses. As the second most prevalent group, unique fungal communities are found across the dry, moist, and oily microenvironments of human skin, and alterations of these communities are largely driven by changes in skin physiology throughout an individual's lifespan. Fungi have also been associated with infection and dermatological disorders, resulting from the disrupted balance between fungal-bacterial networks on the skin.

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Background: Lower extremity amputations from diabetic foot ulcers (DFUs) are rebounding, and new biomarkers that predict wound healing are urgently needed. Anaerobic bacteria have been associated with persistent ulcers and may be a promising biomarker beyond currently recommended vascular assessments. It is unknown whether anaerobic markers are simply a downstream outcome of peripheral arterial disease (PAD) and ischemia, however.

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The skin microbiome is a key player in human health, with diverse functions ranging from defense against pathogens to education of the immune system. While recent studies have begun to shed light on the valuable role that skin microorganisms have in maintaining the skin barrier, a detailed understanding of the complex interactions that shape healthy skin microbial communities is limited. Cobamides, the vitamin B class of cofactor, are essential for organisms across the tree of life.

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Candida auris spreads person to person in hospitals and other healthcare facilities. The heightened capacity for C. auris to colonize skin contributes to the difficulty in eradicating this drug-resistant and deadly pathogen in nosocomial settings.

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