Identification and mechanistic basis of non-ACE2 blocking neutralizing antibodies from COVID-19 patients with deep RNA sequencing and molecular dynamics simulations.

Variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continue to cause disease and impair the effectiveness of treatments. The therapeutic potential of convergent neutralizing antibodies (NAbs) from fully recovered patients has been explored in several early stages of novel drugs. Here, we identified initially elicited NAbs (Ig Heavy, Ig lambda, Ig kappa) in response to COVID-19 infection in patients admitted to the intensive care unit at a single center with deep RNA sequencing (>100 million reads) of peripheral blood as a diagnostic tool for predicting the severity of the disease and as a means to pinpoint specific compensatory NAb treatments.

Deep RNA sequencing of intensive care unit patients with COVID-19.

COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host's response in COVID-19.

Altered transcriptional responses in the lungs of aged mice after influenza infection.

Background: Influenza causes a serious infection in older individuals who are at the highest risk for mortality from this virus. Changes in the immune system with age are well known. This study used transcriptomic analysis to evaluate how aging specifically affects the functional host response to influenza in the lung.

Deep RNA Sequencing of Intensive Care Unit Patients with COVID-19.

Purpose: COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host's response in COVID-19.

Hyperammonemia syndrome due to Ureaplasma urealyticum in a kidney transplant recipient: A case of disseminated disease from a fluoroquinolone-resistant isolate.

Ureaplasma species (spp.) are common colonizers of the urogenital tract but may cause systemic infection in immunocompromised patients. They release significant amounts of ammonia via urea hydrolysis and have been recently implicated in the pathogenesis of hyperammonemia syndrome after organ transplantation.

A predicted DXD-motif glycosyltransferase blocks immune activation.

Pathogens enhance their survival during infections by manipulating host defenses. evades innate immune responses, which we have found to be dependent on an understudied gene (FTL_0883/FTT_0615c). To understand the function of YbeX, we sought protein interactors in subsp.

The Infectious Diseases Society of America's 10 × '20 Initiative (10 New Systemic Antibacterial Agents US Food and Drug Administration Approved by 2020): Is 20 × '20 a Possibility?

Background: Infections caused by antibiotic-resistant bacteria, including carbapenem-resistant Enterobacteriaceae, have increased in frequency, resulting in significant patient morbidity and mortality. The Infectious Diseases Society of America continues to propose legislative, regulatory, and funding solutions to address this escalating crisis. This report updates the status of development and approval of systemic antibiotics in the United States as of late 2018.

Group A streptococcus acute otitis media progressing to neuroinvasive disease in adults.

Acute otitis media affects 700 million people each year with children being disproportionately affected relative to adults. Group A streptococcus is a pathogen implicated in a broad array of human pathology. It is, however, a rare cause of acute otitis media and neuroinvasive disease in older adults with only 2-3 cases occurring per year in the United States.

Characterization of a Francisella tularensis-Caenorhabditis elegans Pathosystem for the Evaluation of Therapeutic Compounds.

is a highly infectious Gram-negative intracellular pathogen that causes tularemia. Because of its potential as a bioterrorism agent, there is a need for new therapeutic agents. We therefore developed a whole-animal - pathosystem for high-throughput screening to identify and characterize potential therapeutic compounds.

Ebola Virus Persistence in Semen of Male Survivors.

We investigated the duration of Ebola virus (EBOV) RNA and infectious EBOV in semen specimens of 5 Ebola virus disease (EVD) survivors. EBOV RNA and infectious EBOV was detected by real-time RT-PCR and virus culture out to 290 days and 70 days, respectively, after EVD onset.

ModuleBlast: identifying activated sub-networks within and across species.

Identifying conserved and divergent response patterns in gene networks is becoming increasingly important. A common approach is integrating expression information with gene association networks in order to find groups of connected genes that are activated or repressed. In many cases, researchers are also interested in comparisons across species (or conditions).

Challenges and future in vaccines, drug development, and immunomodulatory therapy.

Pulmonary diseases and infections are among the top contributors to human morbidity and mortality worldwide, and despite the successful history of vaccines and antimicrobial therapeutics, infectious disease still presents a significant threat to human health. Effective vaccines are frequently unavailable in developing countries, and successful vaccines have yet to be developed for major global maladies, such as tuberculosis. Furthermore, antibiotic resistance poses a growing threat to human health.

Rapid optical determination of β-lactamase and antibiotic activity.

Background: The absence of rapid tests evaluating antibiotic susceptibility results in the empirical prescription of antibiotics. This can lead to treatment failures due to escalating antibiotic resistance, and also furthers the emergence of drug-resistant bacteria. This study reports a rapid optical method to detect β-lactamase and thereby assess activity of β-lactam antibiotics, which could provide an approach for targeted prescription of antibiotics.

The contribution of the glycine cleavage system to the pathogenesis of Francisella tularensis.

Biosynthesis and acquisition of nutrients during infection are integral to pathogenesis. Members of a metabolic pathway, the glycine cleavage system, have been identified in virulence screens of the intracellular bacterium Francisella tularensis but their role in pathogenesis remains unknown. This system generates 5,10-methylenetetrahydrofolate, a precursor of amino acid and DNA synthesis, from glycine degradation.

The use of resazurin as a novel antimicrobial agent against Francisella tularensis.

The highly infectious and deadly pathogen, Francisella tularensis, is classified by the CDC as a Category A bioterrorism agent. Inhalation of a single bacterium results in an acute pneumonia with a 30-60% mortality rate without treatment. Due to the prevalence of antibiotic resistance, there is a strong need for new types of antibacterial drugs.

MyD88-dependent signaling prolongs survival and reduces bacterial burden during pulmonary infection with virulent Francisella tularensis.

Francisella tularensis is the causative agent of the debilitating febrile illness tularemia. The severe morbidity associated with F. tularensis infections is attributed to its ability to evade the host immune response.

Role of NK cells in host defense against pulmonary type A Francisella tularensis infection.

Pneumonic tularemia is a potentially fatal disease caused by the Category A bioterrorism agent Francisella tularensis. Understanding the pulmonary immune response to this bacterium is necessary for developing effective vaccines and therapeutics. In this study, characterization of immune cell populations in the lungs of mice infected with the type A strain Schu S4 revealed a significant loss in natural killer (NK) cells over time.

Interferon-γ, tumor necrosis factor, and interleukin-18 cooperate to control growth of Mycobacterium tuberculosis in human macrophages.

Mycobacterium tuberculosis (MTB) remains a leading infectious threat to human health. Macrophages are the cells targeted for infection by the bacterium as well as key effector cells for clearance of the pathogen. Interleukin (IL)-27 opposes macrophage-mediated control of MTB because supplying IL-12 and blocking the activity of IL-27 limits bacterial growth in primary human macrophages.

A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS), does not elicit complete protection against lethal challenge with a virulent type A Francisella strain.

Large scale comparison of innate responses to viral and bacterial pathogens in mouse and macaque.

Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens.

A Francisella tularensis locus required for spermine responsiveness is necessary for virulence.

Tularemia is a debilitating febrile illness caused by the category A biodefense agent Francisella tularensis. This pathogen infects over 250 different hosts, has a low infectious dose, and causes high morbidity and mortality. Our understanding of the mechanisms by which F.

Invasion of erythrocytes by Francisella tularensis.

Francisella tularensis is the causative agent of tularemia and is classified as a category A biodefense agent by the Centers for Disease Control and Prevention because of its highly infectious nature. F. tularensis infects leukocytes and exhibits an extracellular phase in the blood of the host.

Presence of adequate intravitreal concentrations of daptomycin after systemic intravenous administration in a patient with endogenous endophthalmitis.

Study Objective: To determine whether daptomycin has the potential to be an effective alternative treatment to vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) endogenous endophthalmitis by measuring daptomycin penetration into the vitreous humor.

Design: Laboratory analysis of serum and intravitreal fluids to quantify the ratio between vitreous humor and serum daptomycin concentrations.

Setting: Critical care unit in a university-affiliated tertiary care medical center.

New vector tools with a hygromycin resistance marker for use with opportunistic pathogens.

The ability of many bacterial strains to tolerate antibiotics can limit the number of molecular tools available for research of these organisms. To help address this problem, we have modified a diverse set of vectors to include a broadly expressed hygromycin resistance (HmR) marker. Hygromycin B is an aminoglycoside antibiotic not used to treat infections in humans and has antimicrobial activity against a wide range of microorganisms.