Elizabeth A Grice

University of Pennsylvania, Filadelfia, Pennsylvania, United States

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Publications (30)282.41 Total impact

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    ABSTRACT: Staphylococcus aureus and other coagulase-positive staphylococci (CPS) colonize skin and mucous membrane sites and can cause skin and soft tissue infections (SSTIs) in humans and animals. Factors modulating methicillin-resistant S. aureus (MRSA) colonization and infection in humans remain unclear, including the role of the greater microbial community and environmental factors such as contact with companion animals. In the context of a parent study evaluating the households of outpatients with community MRSA SSTI, the objectives of this study were 1) to characterize the microbiota that colonizes typical coagulase-positive Staphylococcus spp. carriage sites in humans and their companion pets, 2) to analyze associations between Staphylococcus infection and carriage and the composition and diversity of microbial communities, and 3) to analyze factors that influence sharing of microbiota between pets and humans. We enrolled 25 households containing 56 pets and 30 humans. Sampling locations were matched to anatomical sites cultured by the parent study for MRSA and other CPS. Bacterial microbiota were characterized by sequencing of 16S ribosomal RNA genes. Household membership was strongly associated with microbial communities, in both humans and pets. Pets were colonized with a greater relative abundance of Proteobacteria, whereas people were colonized with greater relative abundances of Firmicutes and Actinobacteria. We did not detect differences in microbiota associated with MRSA SSTI, or carriage of MRSA, S. aureus or CPS. Humans in households without pets were more similar to each other than humans in pet-owning households, suggesting that companion animals may play a role in microbial transfer. We examined changes in microbiota over a 3-month time period and found that pet staphylococcal carriage sites were more stable than human carriage sites. We characterized and identified patterns of microbiota sharing and stability between humans and companion animals. While we did not detect associations with MRSA SSTI, or carriage of MRSA, S. aureus or CPS in this small sample size, larger studies are warranted to fully explore how microbial communities may be associated with and contribute to MRSA and/or CPS colonization, infection, and recurrence.
    12/2015; 3(1):2. DOI:10.1186/s40168-014-0052-7
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    ABSTRACT: Significance: Open fractures are fractures in which the bone has violated the skin and soft tissue. Because of their severity, open fractures are associated with complications that can result in increased lengths of hospital stays, multiple operative interventions, and even amputation. One of the factors thought to influence the extent of these complications is exposure and contamination of the open fracture with environmental microorganisms, potentially those that are pathogenic in nature. Recent Advances: Current open fracture care aims to prevent infection by wound classification, prophylactic antibiotic administration, debridement and irrigation, and stable fracture fixation. Critical Issues: Despite these established treatment paradigms, infections and infection-related complications remain a significant clinical burden. To address this, improvements need to be made in our ability to detect bacterial infections, effectively remove wound contamination, eradicate infections, and treat and prevent biofilm formation associated with fracture fixation hardware. Future Directions: Current research is addressing these critical issues. While culture methods are of limited value, culture-independent molecular techniques are being developed to provide informative detection of bacterial contamination and infection. Other advanced contamination- and infection-detecting techniques are also being investigated. New hardware-coating methods are being developed to minimize the risk of biofilm formation in wounds, and immune stimulation techniques are being developed to prevent open fracture infections.
    01/2015; 4(1):59-74. DOI:10.1089/wound.2014.0531
  • Brendan P Hodkinson, Elizabeth A Grice
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    ABSTRACT: Significance: The colonization of wounds by specific microbes or communities of microbes may delay healing and/or lead to infection-related complication. Studies of wound-associated microbial communities (microbiomes) to date have primarily relied upon culture-based methods, which are known to have extreme biases and are not reliable for the characterization of microbiomes. Biofilms are very resistant to culture and are therefore especially difficult to study with techniques that remain standard in clinical settings. Recent Advances: Culture-independent approaches employing next-generation DNA sequencing have provided researchers and clinicians a window into wound-associated microbiomes that could not be achieved before and has begun to transform our view of wound-associated biodiversity. Within the past decade, many platforms have arisen for performing this type of sequencing, with various types of applications for microbiome research being possible on each. Critical Issues: Wound care incorporating knowledge of microbiomes gained from next-generation sequencing could guide clinical management and treatments. The purpose of this review is to outline the current platforms, their applications, and the steps necessary to undertake microbiome studies using next-generation sequencing. Future Directions: As DNA sequencing technology progresses, platforms will continue to produce longer reads and more reads per run at lower costs. A major future challenge is to implement these technologies in clinical settings for more precise and rapid identification of wound bioburden.
    01/2015; 4(1):50-58. DOI:10.1089/wound.2014.0542
  • Adam SanMiguel, Elizabeth A Grice
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    ABSTRACT: The skin is colonized by an assemblage of microorganisms which, for the most part, peacefully coexist with their hosts. In some cases, these communities also provide vital functions to cutaneous health through the modulation of host factors. Recent studies have illuminated the role of anatomical skin site, gender, age, and the immune system in shaping the cutaneous ecosystem. Alterations to microbial communities have also been associated with, and likely contribute to, a number of cutaneous disorders. This review focuses on the host factors that shape and maintain skin microbial communities, and the reciprocal role of microbes in modulating skin immunity. A greater understanding of these interactions is critical to elucidating the forces that shape cutaneous populations and their contributions to skin homeostasis. This knowledge can also inform the tendency of perturbations to predispose and/or bring about certain skin disorders.
    Cellular and Molecular Life Sciences CMLS 12/2014; 72(8). DOI:10.1007/s00018-014-1812-z
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    ABSTRACT: Wound healing is a complex homeostatic response to injury that engages numerous cellular activities, processes, and cell-to-cell interactions. The complement system, an intricate network of proteins with important roles in immune surveillance and homeostasis, has been implicated in many physiological processes; however, its role in wound healing remains largely unexplored. In this study, we employ a murine model of excisional cutaneous wound healing and show that C3(-/-) mice exhibit accelerated early stages of wound healing. Reconstitution of C3(-/-) mice with serum from C3(+/+) mice or purified human C3 abrogated the accelerated wound-healing phenotype. Wound histology of C3(-/-) mice revealed a reduction in inflammatory infiltrate compared with C3(+/+) mice. C3 deficiency also resulted in increased accumulation of mast cells and advanced angiogenesis. We further show that mice deficient in the downstream complement effector C5 exhibit a similar wound-healing phenotype, which is recapitulated in C5aR1(-/-) mice, but not C3aR(-/-) or C5aR2(-/-) mice. Taken together, these data suggest that C5a signaling through C5aR may in part play a pivotal role in recruitment and activation of inflammatory cells to the wound environment, which in turn could delay the early stages of cutaneous wound healing. These findings also suggest a previously underappreciated role for complement in wound healing, and may have therapeutic implications for conditions of delayed wound healing. Copyright © 2014 by The American Association of Immunologists, Inc.
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    ABSTRACT: This report describes the volatile organic compounds (VOCs) associated with human cerumen (earwax) and the effects of ethnicity/race and variation on the ATP-binding cassette, sub-family C, member 11 gene (ABCC11). A single nucleotide polymorphism (SNP) in ABCC11 affects the cerumen VOC profiles of individuals from African, Caucasian, and Asian descent. Employing gas chromatography/mass spectrometry (GC/MS) we have identified the nature and relative abundance of cerumen VOCs from 32 male donors. Our results show that cerumen contains a complex mixture of VOCs and that the amounts of these compounds vary across individuals as well as across ethnic/racial groups. In six of the seven compounds whose detected concentrations were found to be statistically different across groups, individuals of African descent (AfD) > Caucasian descent (CaD) > Asians descent (AsD). Our findings also reveal that ABCC11 genotype alone does not predict the type and relative levels of volatiles found in human cerumen, and suggest that other biochemical pathways must be involved. Examination of the composition and diversity of external auditory canal microbiota in a small subset of our subject population revealed that the ear microbiota may not be directly correlated with either ethnic group membership or ABCC11 genotype.
    Journal of Chemical Ecology 12/2014; 41(1). DOI:10.1007/s10886-014-0533-y
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    ABSTRACT: Older adults are more likely to have chronic wounds than younger people, and the effect of chronic wounds on quality of life is particularly profound in this population. Wound healing slows with age, but the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The effect of age and accompanying multimorbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables; lack of standardization in data collection; and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this article, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify research questions to guide future study of age-associated changes in chronic wound healing. © 2015 by the American Geriatrics Society and the Wound Healing Society.
    Wound Repair and Regeneration 12/2014; 23(1). DOI:10.1111/wrr.12245
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    Keisha Findley, Elizabeth A Grice
    PLoS Pathogens 10/2014; 10(10):e1004436. DOI:10.1371/journal.ppat.1004436
  • Ana M Misic, Sue E Gardner, Elizabeth A Grice
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    ABSTRACT: Significance: Bacterial burden is believed to play a significant role in impaired wound healing of chronic wounds and the development of infection-related complications. The standard of care in the clinic relies upon cultivation-dependent methods to identify microorganisms. These assays are biased toward microorganisms that thrive in isolation under laboratory conditions. Recent Advances: Significant advances in genomic technologies have enabled less-biased, culture-independent approaches to characterize microbial communities, or microbiomes. The aggregate sequencing and analysis of 16S ribosomal RNA genes has demonstrated that cultures under-represent true microbial diversity and load. Critical Issues: Despite recent advances that enable culture-independent analyses of microbiomes, those organisms that are important in impaired healing remain ambiguous. Inconsistent findings across various studies highlight the need to characterize microbiomes of chronic wounds with homogenous etiology to determine differences in microbiomes that may be driven by the wound environment and that may affect wound outcomes. Rigorous analyses of wound microbiomes in light of the three dimensions of bioburden (microbial diversity, microbial load, and pathogenic organisms), clinical metadata, and wound outcomes will be a significant step forward in our quest to understand the role of microorganisms in impaired healing. Future Directions: Longitudinal studies employing serial sampling are needed to appreciate the role of the dynamic microbial community in chronic wound healing. The value of clinical metadata needs to be examined as potential biomarkers of problematic microbiota and wound outcomes. Lastly, better characterization and understanding of wound microbiomes will open avenues for improved diagnostic and therapeutic tools for the nonhealing wound.
    07/2014; 3(7):502-510. DOI:10.1089/wound.2012.0397
  • Elizabeth A Grice
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    ABSTRACT: A vast diversity of microorganisms, including bacteria, fungi, viruses, and arthropods, colonize the human skin. Culture-independent genomic approaches for identifying and characterizing microbial communities have provided glimpses into the topographical, temporal, and interpersonal complexity that defines the skin microbiome. Identification of changes associated with cutaneous disease, including acne, atopic dermatitis, rosacea, and psoriasis, are being established. In this review, our current knowledge of the skin microbiome in health and disease is discussed, with particular attention to potential opportunities to leverage the skin microbiome as a diagnostic, prognostic, and/or therapeutic tool.
    Seminars in Cutaneous Medicine and Surgery 06/2014; 33(2):98-103. DOI:10.12788/j.sder.0087
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    ABSTRACT: Precise identification of bacteria associated with post-injury infection, co-morbidities, and outcomes could have a tremendous impact in the management and treatment of open fractures. We characterized microbiota colonizing open fractures using culture-independent, high-throughput DNA sequencing of bacterial 16S ribosomal RNA genes, and analyzed those communities with respect to injury mechanism, severity, anatomical site, and infectious complications. Thirty subjects presenting to the Hospital of the University of Pennsylvania for acute care of open fractures were enrolled in a prospective cohort study. Microbiota was collected from wound center and adjacent skin upon presentation to the emergency department, intraoperatively, and at two outpatient follow-up visits at approximately 25 and 50 days following initial presentation. Bacterial community composition and diversity colonizing open fracture wounds became increasingly similar to adjacent skin microbiota with healing. Mechanism of injury, severity, complication, and location were all associated with various aspects of microbiota diversity and composition. The results of this pilot study demonstrate the diversity and dynamism of the open fracture microbiota, and their relationship to clinical variables. Validation of these preliminary findings in larger cohorts may lead to the identification of microbiome-based biomarkers of complication risk and/or to aid in management and treatment of open fractures. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
    Journal of Orthopaedic Research 04/2014; 32(4). DOI:10.1002/jor.22578
  • Geoffrey D Hannigan, Elizabeth A Grice
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    ABSTRACT: The skin is the primary physical barrier between the body and the external environment and is also a substrate for the colonization of numerous microbes. Previously, dermatological microbiology research was dominated by culture-based techniques, but significant advances in genomic technologies have enabled the development of less-biased, culture-independent approaches to characterize skin microbial communities. These molecular microbiology approaches illustrate the great diversity of microbiota colonizing the skin and highlight unique features such as site specificity, temporal dynamics, and interpersonal variation. Disruptions in skin commensal microbiota are associated with the progression of many dermatological diseases. A greater understanding of how skin microbes interact with each other and with their host, and how we can therapeutically manipulate those interactions, will provide powerful tools for treating and preventing dermatological disease.
    Cold Spring Harbor Perspectives in Medicine 12/2013; 3(12). DOI:10.1101/cshperspect.a015362
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    ABSTRACT: The skin is colonized by a plethora of microbes that include commensals and potential pathogens, but it is currently unknown how cutaneous host immune mechanisms influence the composition, diversity, and quantity of the skin microbiota. Here we reveal an interactive role for complement in cutaneous host-microbiome interactions. Inhibiting signaling of the complement component C5a receptor (C5aR) altered the composition and diversity of the skin microbiota as revealed by deep sequencing of the bacterial 16S rRNA gene. In parallel, we demonstrate that C5aR inhibition results in down-regulation of genes encoding cutaneous antimicrobial peptides, pattern recognition receptors, and proinflammatory mediators. Immunohistochemistry of inflammatory cell infiltrates in the skin showed reduced numbers of macrophages and lymphocytes with C5aR inhibition. Further, comparing cutaneous gene expression in germ-free mice vs. conventionally raised mice suggests that the commensal microbiota regulates expression of complement genes in the skin. These findings demonstrate a component of host immunity that impacts colonization of the skin by the commensal microbiota and vice versa, a critical step toward understanding host-microbe immune mutualism of the skin and its implications for health and disease. Additionally, we reveal a role for complement in homeostatic host-microbiome interactions of the skin.
    Proceedings of the National Academy of Sciences 08/2013; DOI:10.1073/pnas.1307855110
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    ABSTRACT: Nonhealing diabetic foot ulcers (DFUs) are a common and costly complication of diabetes. Microbial burden, or "bioburden," is believed to underlie delayed healing, although little is known of those clinical factors that may influence microbial load, diversity, and/or pathogenicity. We profiled the microbiomes of neuropathic nonischemic DFUs without clinical evidence of infection in 52 individuals using high-throughput sequencing of the bacterial 16S ribosomal RNA gene. Comparatively, wound cultures, the standard diagnostic in the clinic, vastly underrepresent microbial load, microbial diversity, and the presence of potential pathogens. DFU microbiomes were heterogeneous, even in our tightly restricted study population, but partitioned into three clusters distinguished primarily by dominant bacteria and diversity. Ulcer depth was associated with ulcer cluster, positively correlated with abundance of anaerobic bacteria, and negatively correlated with abundance of Staphylococcus. Ulcer duration was positively correlated with bacterial diversity, species richness, and relative abundance of Proteobacteria, but was negatively correlated with relative abundance of Staphylococcus. Finally, poor glycemic control was associated with ulcer cluster, with poorest median glycemic control concentrating to Staphylococcus-rich and Streptococcus-rich ulcer clusters. Analyses of microbial community membership and structure may provide the most useful metrics in prospective studies to delineate problematic bioburden from benign colonization that can then be used to drive clinical treatment.
    Diabetes 11/2012; 62(3). DOI:10.2337/db12-0771
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    Elizabeth A Grice, Julia A Segre
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    ABSTRACT: The human genome has been referred to as the blueprint of human biology. In this review we consider an essential but largely ignored overlay to that blueprint, the human microbiome, which is composed of those microbes that live in and on our bodies. The human microbiome is a source of genetic diversity, a modifier of disease, an essential component of immunity, and a functional entity that influences metabolism and modulates drug interactions. Characterization and analysis of the human microbiome have been greatly catalyzed by advances in genomic technologies. We discuss how these technologies have shaped this emerging field of study and advanced our understanding of the human microbiome. We also identify future challenges, many of which are common to human genetic studies, and predict that in the future, analyzing genetic variation and risk of human disease will sometimes necessitate the integration of human and microbial genomic data sets.
    Annual review of genomics and human genetics 06/2012; 13:151-70. DOI:10.1146/annurev-genom-090711-163814
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    ABSTRACT: Atopic dermatitis (AD) has long been associated with Staphylococcus aureus skin colonization or infection and is typically managed with regimens that include antimicrobial therapies. However, the role of microbial communities in the pathogenesis of AD is incompletely characterized. To assess the relationship between skin microbiota and disease progression, 16S ribosomal RNA bacterial gene sequencing was performed on DNA obtained directly from serial skin sampling of children with AD. The composition of bacterial communities was analyzed during AD disease states to identify characteristics associated with AD flares and improvement post-treatment. We found that microbial community structures at sites of disease predilection were dramatically different in AD patients compared with controls. Microbial diversity during AD flares was dependent on the presence or absence of recent AD treatments, with even intermittent treatment linked to greater bacterial diversity than no recent treatment. Treatment-associated changes in skin bacterial diversity suggest that AD treatments diversify skin bacteria preceding improvements in disease activity. In AD, the proportion of Staphylococcus sequences, particularly S. aureus, was greater during disease flares than at baseline or post-treatment, and correlated with worsened disease severity. Representation of the skin commensal S. epidermidis also significantly increased during flares. Increases in Streptococcus, Propionibacterium, and Corynebacterium species were observed following therapy. These findings reveal linkages between microbial communities and inflammatory diseases such as AD, and demonstrate that as compared with culture-based studies, higher resolution examination of microbiota associated with human disease provides novel insights into global shifts of bacteria relevant to disease progression and treatment.
    Genome Research 03/2012; 22(5):850-9. DOI:10.1101/gr.131029.111
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    Elizabeth A Grice, Julia A Segre
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    ABSTRACT: Microbes colonizing and/or infecting chronic wounds undoubtedly play a major and interactive role in impaired healing, especially in amplifying and perpetuating the host innate immune response. The development of molecular techniques to identify and quantify microbial organisms has revolutionized our view of the microbial world. These less-biased, high throughput methods greatly enable investigations regarding host-microbe interactions in the chronic wound environment. This review focuses on the mounting evidence implicating microbes and excessive inflammation in chronic wounds, as well as the challenges associated with understanding how microbes modulate wound healing and the innate immune response.
    Advances in Experimental Medicine and Biology 01/2012; 946:55-68. DOI:10.1007/978-1-4614-0106-3_4
  • Elizabeth A Grice, Julia A Segre
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    ABSTRACT: The skin is the human body's largest organ, colonized by a diverse milieu of microorganisms, most of which are harmless or even beneficial to their host. Colonization is driven by the ecology of the skin surface, which is highly variable depending on topographical location, endogenous host factors and exogenous environmental factors. The cutaneous innate and adaptive immune responses can modulate the skin microbiota, but the microbiota also functions in educating the immune system. The development of molecular methods to identify microorganisms has led to an emerging view of the resident skin bacteria as highly diverse and variable. An enhanced understanding of the skin microbiome is necessary to gain insight into microbial involvement in human skin disorders and to enable novel promicrobial and antimicrobial therapeutic approaches for their treatment.
    Nature Reviews Microbiology 04/2011; 9(4):244-53. DOI:10.1038/nrmicro2537
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    Genome Biology 10/2010; 11(Suppl 1). DOI:10.1186/gb-2010-11-s1-i18
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    ABSTRACT: Diabetics frequently suffer from chronic, nonhealing wounds. Although bacterial colonization and/or infection are generally acknowledged to negatively impact wound healing, the precise relationship between the microbial community and impaired wound healing remains unclear. Because the host cutaneous defense response is proposed to play a key role in modulating microbial colonization, we longitudinally examined the diabetic wound microbiome in tandem with host tissue gene expression. By sequencing 16S ribosomal RNA genes, we show that a longitudinal selective shift in wound microbiota coincides with impaired healing in diabetic mice (Lepr(db/db); db/db). We demonstrate a parallel shift in longitudinal gene expression that occurs in a cluster of genes related to the immune response. Further, we establish a correlation between relative abundance of Staphylococcus spp. and the expression of cutaneous defense response genes. Our data demonstrate that integrating two types of global datasets lends a better understanding to the dynamics governing host-microbe interactions.
    Proceedings of the National Academy of Sciences 08/2010; 107(33):14799-804. DOI:10.1073/pnas.1004204107

Publication Stats

2k Citations
282.41 Total Impact Points

Institutions

  • 2012–2015
    • University of Pennsylvania
      • Department of Dermatology
      Filadelfia, Pennsylvania, United States
  • 2013–2014
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2008–2012
    • National Human Genome Research Institute
      Maryland, United States
  • 2005–2006
    • Johns Hopkins University
      • McKusick-Nathans Institute of Genetic Medicine
      Baltimore, Maryland, United States