Publications by authors named "Lindsay R Kalan"

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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Article Synopsis
  • In 2019, concerns were raised by the International Working Group on the Diabetic Foot about using molecular microbiology techniques for diagnosing infections in diabetic foot ulcers, which this review aims to address.
  • Recent studies have demonstrated that metagenomic and metatranscriptomic approaches can be applied to diabetic foot ulcer samples, but they featured small sample sizes and potential biases, indicating a need for larger longitudinal research.
  • Currently, high-throughput molecular microbiology techniques are not suitable for clinical use as routine diagnostics, but advancements in these technologies could enhance patient care in the future.
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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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  • 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 commonly used in burn healing research, but anatomical locations and inconsistent wound methods can skew results.
  • The study aims to analyze how the anatomical location impacts burn creation and healing, using euthanized and live pigs to assess differences in burn depth and healing times based on location.
  • Findings reveal that ventral skin suffers deeper burns and exhibits slower healing compared to dorsal skin, underscoring the need for consistent treatment strategies and careful consideration of anatomical sites in research to improve the relevance of results for human applications.
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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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  • skDER is a tool that combines techniques to efficiently estimate Average Nucleotide Identity (ANI) among many microbial genomes, employing a low-memory dereplication method.
  • It features two main approaches: a dynamic algorithm that selects a concise set of representative genomes for tracking strains in microbiome samples, and a greedy method that reduces redundancy for comparative genomics, enabling better analytical efficiency.
  • Additionally, skDER allows users to automatically download genomes of specific species or genera from the Genome Taxonomy Database and provides precomputed representative genomes for commonly studied bacterial groups.
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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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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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The skin microbiome is essential for skin function, yet the mechanisms responsible are only beginning to be uncovered. In this issue of Cell Host & Microbe, Zheng et al. demonstrate that a Staphylococcus epidermidis sphingomyelinase has a mutually beneficial role in supporting the skin barrier and promoting S.

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Polymicrobial biofilms are a hallmark of chronic wound infection. The forces governing assembly and maturation of these microbial ecosystems are largely unexplored but the consequences on host response and clinical outcome can be significant. In the context of wound healing, formation of a biofilm and a stable microbial community structure is associated with impaired tissue repair resulting in a non-healing chronic wound.

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Human skin functions as a physical, chemical, and immune barrier against the external environment while also providing a protective niche for its resident microbiota, known as the skin microbiome. Cooperation between the microbiota, host skin cells, and the immune system is responsible for maintenance of skin health, and a disruption to this delicate balance, such as by pathogen invasion or a breach in the skin barrier, may lead to impaired skin function. In this minireview, we describe the role of the microbiome in microbe, host, and immune interactions under distinct skin states, including homeostasis, tissue repair, and wound infection.

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Emerging pathogen causes nosocomial outbreaks of life-threatening invasive candidiasis. It is unclear how this species colonizes skin and spreads in health care facilities. Here, we analyzed growth in synthetic sweat medium designed to mimic axillary skin conditions.

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Background: Canine otitis externa (OE) is a common inflammatory disease that is frequently complicated by secondary bacterial and/or yeast infections. The otic microbial population is more complex than appreciated by cytological methods and aerobic culture alone.

Hypothesis/objectives: Differences in bacterial and fungal populations of the external ear canal will correlate with specific cytological and culture-based definitions of bacterial and Malassezia otitis.

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Chronic wounds are a major complication of diabetes associated with high morbidity and health care expenditures. To investigate the role of colonizing microbiota in diabetic wound healing, clinical outcomes, and response to interventions, we conducted a longitudinal, prospective study of patients with neuropathic diabetic foot ulcers (DFU). Metagenomic shotgun sequencing revealed that strain-level variation of Staphylococcus aureus and genetic signatures of biofilm formation were associated with poor outcomes.

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