The US Department of Veterans Affairs Science and Health Initiative to Combat Infectious and Emerging Life-Threatening Diseases (VA SHIELD): A Biorepository Addressing National Health Threats.

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has demonstrated the need to share data and biospecimens broadly to optimize clinical outcomes for US military Veterans.

Methods: In response, the Veterans Health Administration established VA SHIELD (Science and Health Initiative to Combat Infectious and Emerging Life-threatening Diseases), a comprehensive biorepository of specimens and clinical data from affected Veterans to advance research and public health surveillance and to improve diagnostic and therapeutic capabilities.

Results: VA SHIELD now comprises 12 sites collecting de-identified biospecimens from US Veterans affected by SARS-CoV-2.

Regulation of virulence and antibiotic resistance in Gram-positive microbes in response to cell wall-active antibiotics.

Purpose Of Review: Antibiotic stress can evoke considerable genotypic and phenotypic changes in Gram-positive bacteria. Here, we review recent studies describing altered virulence expression in response to cell wall-acting antibiotics and discuss mechanisms that coordinate regulation of the antibiotic response.

Recent Findings: Pleiotropic effects induced by antibiotic exposure include alterations to bacterial metabolism, cell wall structure and antibiotic resistance.

Subinhibitory concentrations of tedizolid potently inhibit extracellular toxin production by methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Purpose: Potent extracellular toxins including alpha-haemolysin, Panton-Valentine leukocidin (PVL) and toxic-shock syndrome toxin 1 (TSST-1) significantly contribute to Staphylococcus aureus pathogenesis, thus, toxin suppression is a primary focus in treatment of staphylococcal disease. S. aureus maintains complex strategies to regulate toxin expression and previous data have demonstrated that subinhibitory concentrations of beta-lactam antibiotics can adversely increase S.

Subinhibitory Dalbavancin Attenuates Exotoxin Production from Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus .

This study investigated the effects of subinhibitory doses of the lipoglycopeptide antibiotic dalbavancin on toxin production toxin production levels were compared to those seen with the natural glycopeptide antibiotic vancomycin and with representative beta-lactam and oxazolidinone antibiotics. While neither dalbavancin nor vancomycin adversely affected toxin production, of these glycopeptide antibiotics, only dalbavancin significantly attenuated toxin production at subinhibitory concentrations. These findings support the recent success of dalbavancin for treatment of staphylococcal infections.

Cardiac myocyte dysfunction induced by streptolysin O is membrane pore and calcium dependent.

Septic cardiomyopathy is a severe complication among some patients who develop group A streptococcal toxic shock syndrome. Despite the importance of cardiac dysfunction in determining prognosis, very little is known about mechanisms that reduce cardiac output in association with streptococcal infection. Here, we investigated the effects of streptococcal extracellular toxins on mechanical contractility of electrically paced primary murine cardiomyocytes.

Staphylococcus aureus α-hemolysin promotes platelet-neutrophil aggregate formation.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes severe hemorrhagic necrotizing pneumonia associated with high mortality. Exotoxins have been implicated in the pathogenesis of this infection; however, the cellular mechanisms responsible remain largely undefined. Because platelet-neutrophil aggregates (PNAs) can dysregulate inflammatory responses and contribute to tissue destruction, we investigated whether exotoxins from MRSA could stimulate formation of PNAs in human whole blood.

A conserved PMK-1/p38 MAPK is required in caenorhabditis elegans tissue-specific immune response to Yersinia pestis infection.

Yersinia pestis has acquired a variety of complex strategies that enable the bacterium to overcome defenses in different hosts and ensure its survival and successful transmission. A full-genome microarray analysis on Caenorhabditis elegans infected with Y. pestis shows enrichment in genes that are markers of innate immune responses and regulated by a conserved PMK-1/p38 MAPK.

Dual role of MyD88 in rapid clearance of relapsing fever Borrelia spp.

Relapsing fever Borrelia spp. undergo antigenic variation, achieve high levels in blood, and require rapid production of immunoglobulin M (IgM) for clearance. MyD88-deficient mice display defective clearance of many pathogens; however, the IgM response to persistent infection is essentially normal.

Molecular mimicry to Borrelia burgdorferi: pathway to autoimmunity?

Lyme borreliosis is due to infection with the tick-borne spirochete Borrelia burgdorferi, and is associated with persistent infection unless treated with antibiotics. The persistent nature of infection by B. burgdorferi can lead to development of chronic disease, as found in patients infected before recognition of the effectiveness of antibiotic therapy.

MyD88 plays a unique role in host defense but not arthritis development in Lyme disease.

To assess the contribution of TLR signaling in the host response to Borrelia burgdorferi, mice deficient in the common TLR adaptor protein, myeloid differentiation factor 88 (MyD88), were infected with B. burgdorferi. MyD88-deficient mice harbored extremely high levels of B.