Eric P. Skaar is an American microbiologist, the Ernest W. Goodpasture Professor of Pathology, Microbiology and Immunology at Vanderbilt University Medical Center, and a University Distinguished Professor at Vanderbilt University.
Eric P. Skaar | |
---|---|
Born | 1974 |
Nationality | American |
Title | Director, Vanderbilt Institute for Infection, Immunology, and Inflammation (VI4), Ernest W. Goodpasture Professor of Pathology, Vice Chair for Basic Research |
Academic background | |
Academic advisors | Olaf Schneewind, Hank Seifert |
Academic work | |
Discipline | Pathology,Microbiology,Immunology |
Institutions | Vanderbilt University Medical Center |
Skaar earned his Bachelor of Science degree in Bacteriology at the University of Wisconsin-Madison in 1996,and his Ph.D. in Immunology and Microbial Pathogenesis and Master’s Degree in Public Health in Biostatistics and Epidemiology at Northwestern University in 2002. After completing a postdoctoral fellowship in Microbiology at the University of Chicago,Skaar joined the Vanderbilt faculty in 2005 as an assistant professor,and was named to the endowed Ernest W. Goodpasture Chair in Pathology in 2012. [1]
He is the Vice Chair for Research in the Department of Pathology,Microbiology and Immunology,and the Director of the Vanderbilt Institute for Infection,Immunology,and Inflammation (VI4). [2]
The Skaar laboratory focuses on nutritional immunity which studies that aspect of the innate immune response to infectious diseases. They have studied (i) nutrient acquisition by bacterial pathogens,(ii) how vertebrate immune proteins sequester nutrients during the pathogenesis of infection and cancer,(iii) competition for nutrients between pathogens and the healthy microbiome,and (iv) the impact of diet on infection. [2] His research has resulted in approximately 250 published research articles.
In order for bacterial pathogens to cause disease,they must obtain nutrients inside their vertebrate hosts. The primary nutrients that are limiting to the growth of bacteria inside vertebrates are metals,because vertebrates have developed numerous metal chelation systems that serve as a host defense against microbial infection. This is one of the aspects of the general concept called nutritional immunity. The Skaar laboratory is interested in identifying the host and bacterial factors that are involved in this competition for metal during the host-pathogen interaction. In particular,they focus on diseases caused by the human pathogens Staphylococcus aureus ,Acinetobacter baumannii, Bacillus anthracis (Anthrax),i,and Clostridioides difficile. The long term goal of the research is to develop novel therapies to treat microbial diseases. [2]
Dr. Skaar and his team discovered that the innate immune protein calprotectin inhibits microbial growth through manganese binding,representing the first example of the host immune system sequestering manganese to inhibit microbial growth . [3] Dr. Skaar,in collaboration with Dr. David Giedroc,reported the first example of a vertebrate zinc metallochaperone which they named ZNG1. ZNG1 is responsible for transferring zinc to METAP1,a critical metalloprotein involved in regulating protein activity across eukaryotes. [4]
Awards
Skaar is a Fellow of the American Academy of Microbiology (ASM) and the American Association for the Advancement of Science (AAAS). [1] He has also been the recipient of the Pfizer Aspire Award,the Searle Scholars Award,the ICAAC/IDSA Young Investigator Award,the Chancellor’s award for Research,the Stanley Cohen Award for Research,and was named a Burroughs Wellcome Investigator in the Pathogenesis of Infectious Diseases.
Weiss A,... Skaar EP (2022). Zn-regulated GTPase metalloprotein activator 1 modulates vertebrate zinc homeostasis. Cell 185 (12),pgs:2148-2163. [4]
Zackular JP,... Skaar EP (2016). Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection. [5] Nature medicine 22 (11),pgs:1330-1334
Cassat JE,Skaar EP (2013). Iron in Infection and Immunity. [6] Cell host µbe 13 (5),pgs:509-519
Hood MI,Skaar EP (2012). Nutritional immunity:transition metals at the pathogen–host interface. [7] Nature Reviews Microbiology 10 (8),pgs:525-537
Corbin BD,... Skaar EP (2008). Metal Chelation and Inhibition of Bacterial Growth in Tissue Abscesses. [3] Science 305 (5690),pgs:1626-1628
Skaar EP,... Schneewind O (2004). Iron-Source Preference of Staphylococcus aureus Infections. [8] Science 305 (5690),pgs:1626-1628
The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens,from viruses to parasitic worms,as well as cancer cells and objects such as wood splinters,distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.
Koch's postulates are four criteria designed to establish a causal relationship between a microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884,based on earlier concepts described by Jakob Henle,and the statements were refined and published by Koch in 1890. Koch applied the postulates to describe the etiology of cholera and tuberculosis,both of which are now ascribed to bacteria. The postulates have been controversially generalized to other diseases. More modern concepts in microbial pathogenesis cannot be examined using Koch's postulates,including viruses and asymptomatic carriers. They have largely been supplanted by other criteria such as the Bradford Hill criteria for infectious disease causality in modern public health and the Molecular Koch's postulates for microbial pathogenesis.
The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside,including the gastrointestinal tract,skin,mammary glands,seminal fluid,uterus,ovarian follicles,lung,saliva,oral mucosa,conjunctiva,and the biliary tract. Types of human microbiota include bacteria,archaea,fungi,protists,and viruses. Though micro-animals can also live on the human body,they are typically excluded from this definition. In the context of genomics,the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms;however,the term human metagenome has the same meaning.
Neutrophils are a type of white blood cell. More specifically,they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system,with their functions varying in different animals.
The adaptive immune system,also known as the acquired immune system,or specific immune system is a subsystem of the immune system that is composed of specialized,systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.
An opportunistic infection is an infection caused by pathogens that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources,such as a weakened immune system,an altered microbiome,or breached integumentary barriers. Many of these pathogens do not necessarily cause disease in a healthy host that has a non-compromised immune system,and can,in some cases,act as commensals until the balance of the immune system is disrupted. Opportunistic infections can also be attributed to pathogens which cause mild illness in healthy individuals but lead to more serious illness when given the opportunity to take advantage of an immunocompromised host.
Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes,but not present in the host. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. This allows the innate immune system to recognize pathogens and thus,protect the host from infection.
In cell biology,a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages,neutrophils,and dendritic cells (DCs).
Intracellular parasites are microparasites that are capable of growing and reproducing inside the cells of a host. They are also called intracellular pathogens.
The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants,fungi,prokaryotes,and invertebrates.
Virulence factors are cellular structures,molecules and regulatory systems that enable microbial pathogens to achieve the following:
Porphyromonas gingivalis belongs to the phylum Bacteroidota and is a nonmotile,Gram-negative,rod-shaped,anaerobic,pathogenic bacterium. It forms black colonies on blood agar.
Pathogenic bacteria are bacteria that can cause disease. This article focuses on the bacteria that are pathogenic to humans. Most species of bacteria are harmless and are often beneficial but others can cause infectious diseases. The number of these pathogenic species in humans is estimated to be fewer than a hundred. By contrast,several thousand species are part of the gut flora present in the digestive tract.
Microbiota are the range of microorganisms that may be commensal,mutualistic,or pathogenic found in and on all multicellular organisms,including plants. Microbiota include bacteria,archaea,protists,fungi,and viruses,and have been found to be crucial for immunologic,hormonal,and metabolic homeostasis of their host.
Cellular microbiology is a discipline that bridges microbiology and cell biology.
In molecular biology,the guanylate-binding proteins family is a family of GTPases that is induced by interferon (IFN)-gamma. GTPases induced by IFN-gamma are key to the protective immunity against microbial and viral pathogens. These GTPases are classified into three groups:the small 47-KD immunity-related GTPases (IRGs),the Mx proteins,and the large 65- to 67-kd GTPases. Guanylate-binding proteins (GBP) fall into the last class.
Colonization resistance is the mechanism whereby the intestinal microbiota protects itself against incursion by new and often harmful microorganisms.
In biology,a pathogen,in the oldest and broadest sense,is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent,or simply a germ.
Bacterial effectors are proteins secreted by pathogenic bacteria into the cells of their host,usually using a type 3 secretion system (TTSS/T3SS),a type 4 secretion system (TFSS/T4SS) or a Type VI secretion system (T6SS). Some bacteria inject only a few effectors into their host’s cells while others may inject dozens or even hundreds. Effector proteins may have many different activities,but usually help the pathogen to invade host tissue,suppress its immune system,or otherwise help the pathogen to survive. Effector proteins are usually critical for virulence. For instance,in the causative agent of plague,the loss of the T3SS is sufficient to render the bacteria completely avirulent,even when they are directly introduced into the bloodstream. Gram negative microbes are also suspected to deploy bacterial outer membrane vesicles to translocate effector proteins and virulence factors via a membrane vesicle trafficking secretory pathway,in order to modify their environment or attack/invade target cells,for example,at the host-pathogen interface.
Siderocalin(Scn),lipocalin-2,NGAL,24p3 is a mammalian lipocalin-type protein that can prevent iron acquisition by pathogenic bacteria by binding siderophores,which are iron-binding chelators made by microorganisms. Iron serves as a key nutrient in host-pathogen interactions,and pathogens can acquire iron from the host organism via synthesis and release siderophores such as enterobactin. Siderocalin is a part of the mammalian defence mechanism and acts as an antibacterial agent. Crystallographic studies of Scn demonstrated that it includes a calyx,a ligand-binding domain that is lined with polar cationic groups. Central to the siderophore/siderocalin recognition mechanism are hybrid electrostatic/cation-pi interactions. To evade the host defences,pathogens evolved to produce structurally varied siderophores that would not be recognized by siderocalin,allowing the bacteria to acquire iron.