West Nile Virus–infected Mosquitoes, Louisiana, 2002

Culex quinquefasciatus was identified as probable vector

The MMC BioBank is a Resource that Supports Biomedical Research

Mission: To provide normal and diseased annotated human biospecimens to the research community that supports discoveries leading to improved patient therapies and advances in personalized medicine.https://knowledgeconnection.mainehealth.org/lambrew-retreat-2021/1052/thumbnail.jp

Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

<p>Abstract</p> <p>Background</p> <p>Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.</p> <p>Methods</p> <p>To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.</p> <p>Results</p> <p>We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the <it>in vitro</it> and <it>in vivo</it> findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized <it>B. anthracis </it>spores and 30 min post exposure to a bacterial toxin.</p> <p>Conclusion</p> <p>Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.</p

The Role of relA and spoT in Yersinia pestis KIM5+ Pathogenicity

The ppGpp molecule is part of a highly conserved regulatory system for mediating the growth response to various environmental conditions. This mechanism may represent a common strategy whereby pathogens such as Yersinia pestis, the causative agent of plague, regulate the virulence gene programs required for invasion, survival and persistence within host cells to match the capacity for growth. The products of the relA and spoT genes carry out ppGpp synthesis. To investigate the role of ppGpp on growth, protein synthesis, gene expression and virulence, we constructed a ΔrelA ΔspoT Y. pestis mutant. The mutant was no longer able to synthesize ppGpp in response to amino acid or carbon starvation, as expected. We also found that it exhibited several novel phenotypes, including a reduced growth rate and autoaggregation at 26°C. In addition, there was a reduction in the level of secretion of key virulence proteins and the mutant was>1,000-fold less virulent than its wild-type parent strain. Mice vaccinated subcutaneously (s.c.) with 2.5×104 CFU of the ΔrelA ΔspoT mutant developed high anti-Y. pestis serum IgG titers, were completely protected against s.c. challenge with 1.5×105 CFU of virulent Y. pestis and partially protected (60% survival) against pulmonary challenge with 2.0×104 CFU of virulent Y. pestis. Our results indicate that ppGpp represents an important virulence determinant in Y. pestis and the ΔrelA ΔspoT mutant strain is a promising vaccine candidate to provide protection against plague

A permeability Mutant of Yersinia pestis with Increased Susceptibility to Phagocytosis which Retains Potential for Intraphagocytic Growth and Virulence.

Abstract Gentian violet resistance was used to select mutants of Yersinia pestis with altered cell envelope permeability. Mutants in one class lacked the 6 and 61 megadalton (Mdal) plasmids, but retained the 47 Mdal plasmid associated with calcium dependence. Mutants in a second class retained all three plasmids. One mutant in the latter class, EV76S7, lacked major outer membrane protein J and yielded reduced levels of minor outer membrane proteins A and C. Protein J is known to interact differently with lipopolysaccharide (LPS) from cells bearing and cells lacking the 47 Mdal plasmid following growth at 37 degrees C. The 47 Mdal plasmid is known to influence gentian violet uptake, novobiocin sensitivity, susceptibility to phagocytosis, the growth in macrophages and the virulence of Y. pestis. Gentian violet uptake was lower and novobiocin sensitivity higher in the mutant than in the parental strain, but the underlying effects of the 47 Mdal plasmid on these parameters had not changed. EV76S7 cells were phagocytized to a greater extent than the parental cells following growth at 37 degrees C, but survival and growth within peritoneal phagocytes and the LD50's of cells with and without the 47 Mdal plasmid were not altered by the loss of protein J, we conclude that protein J--LPS interactions are not required for virulence, and that the reduced virulence of cells lacking the 47 Mdal plasmid does not result from the altered protein J--LPS interactions which are known to result from loss of the plasmid