Anthrax is caused by the spore-forming, gram-positive bacterium Bacillus anthracis. The bacterium's major virulence factors are (a) the anthrax toxins and (b) an antiphagocytic polyglutamic capsule. These are encoded by two large plasmids, the former by pXO1 and the latter by pXO2. The expression of both is controlled by the bicarbonate-responsive transcriptional regulator, AtxA. The anthrax toxins are three polypeptides—protective antigen (PA), lethal factor (LF), and edema factor (EF)—that come together in binary combinations to form lethal toxin and edema toxin. PA binds to cellular receptors to translocate LF (a protease) and EF (an adenylate cyclase) into cells. The toxins alter cell signaling pathways in the host to interfere with innate immune responses in early stages of infection and to induce vascular collapse at late stages. This review focuses on the role of anthrax toxins in pathogenesis. Other virulence determinants, as well as vaccines and therapeutics, are briefly discussed.

Significance: Understanding microbial population dynamics during infection has important implications for disease management, transmission, and pathogen evolution. A quantitative analysis of microbial population structure requires the ability to track individual strains. We used a pool of individually barcoded strains to measure changes inBrucella abortuspopulation structure during infection of bovine hosts via the ocular conjunctiva, a natural route of entry. Cattle exert a severe bottleneck on the bacterial population entering through the conjunctival mucosa such that individual cells have a 0.0001 probability of colonizing a local draining lymph node. The populations in lymph nodes, even on different sides of the same animal, are distinct and dominated by a small number of highly abundant, spatially distinct clones.

Inflammasomes act as sensors of infection or damage to initiate immune responses. While extensively studied in rodents, understanding of livestock inflammasomes is limited. The NLRP1 inflammasome sensor in rodents is activated by Toxoplasma gondii, Bacillus anthracis lethal toxin (LT), and potentially other zoonotic pathogens. LT activates NLRP1 by N-terminal proteolysis, inducing macrophage pyroptosis and a pro-inflammatory cytokine response. In contrast, NLRP1 in macrophages from humans and certain rodent strains is resistant to LT cleavage, and pyroptosis is not induced. Evolution of NLRP1 sequences towards those leading to pyroptosis is of interest in understanding innate immune responses in different hosts. We characterized NLRP1 in cattle (Bos taurus) and American bison (Bison bison). Bovine NLRP1 is not cleaved by LT, and cattle and bison macrophages do not undergo toxin-induced pyroptosis. Additionally, we found a predicted Nlrp1 splicing isoform in cattle macrophages lacking the N-terminal domain. Resistance to LT in bovine and human NLRP1 correlates with evolutionary sequence similarity to rodents. Consistent with LT-resistant rodents, bovine macrophages undergo a slower non-pyroptotic death in the presence of LPS and LT. Overall, our findings support the model that NLRP1 activation by LT requires N-terminal cleavage, and provide novel information on mechanisms underlying immune response diversity.

For many years, the nonprofit research community and practitioner sector have existed in two distinct silos, which has resulted in the limited influence of research findings on how capacity building is practiced in the field. At the same time, nonprofit research is often conducted in isolation of nonprofit practice, which contributes to practice often based on anecdote and conventional wisdom. With the goal of bridging the two sectors and influencing the field with research to practice, the Alliance for Nonprofit Managementand the Pracademics section of the Association for Research on Nonprofit Organizations and Voluntary Actionorganized a joint initiative to promote research to practice and work together to influence the nonprofit sector. As a first step, the two organizations hosted a half-day working session to identify possible strategies for working together to develop a new model of research-to-practice collaboration, and take concrete steps in informing practice with research. Subscribe to JNEL For many years, the nonprofit research community and practitioner sector have existed in two distinct silos, which has resulted in the limited influence of research findings on how capacity building is practiced in the field. At the same time, nonprofit research is often conducted in isolation of nonprofit practice, which contributes to practice often based on anecdote and conventional wisdom. With the goal of bridging the two sectors and influencing the field with research to practice, the Alliance for Nonprofit Managementand the Pracademics section of the Association for Research on Nonprofit Organizations and Voluntary Actionorganized a joint initiative to promote research to practice and work together to influence the nonprofit sector. As a first step, the two organizations hosted a half-day working session to identify possible strategies for working together to develop a new model of research-to-practice collaboration, and take concrete steps in informing practice with research. Subscribe to JNEL