共查询到11条相似文献,搜索用时 15 毫秒
1.
Malaria, caused by Plasmodium spp., is responsible for over 200 million infections worldwide and 650,000 deaths annually. Until recently, it was thought that blood-stage parasites survived and replicated in hepatocytes and red blood cells exclusively. We recently showed that blood-stage parasites could infect, survive and replicate within plasmacytoid dendritic cells of the spleen and that these cells could release infective parasites. Here we discuss the implications of this novel niche in the spleen. 相似文献
2.
Staphylococcus aureus bacteraemia remains very difficult to treat, and a large proportion of cases result in potentially lethal metastatic infection. Unpredictable and persistent bacteraemia in the face of highly active, usually bactericidal antibiotics is the strongest predictor of death or disseminated disease. Although S. aureus has conventionally been considered an extracellular pathogen, much evidence demonstrates that it can survive intracellularly. In this Opinion article, we propose that phagocytes, and specifically neutrophils, represent a privileged site for S. aureus in the bloodstream, offering protection from most antibiotics and providing a mechanism by which the bacterium can travel to and infect distant sites. Furthermore, we suggest how this can be experimentally confirmed and how it may prompt a change in the current paradigm of S. aureus bacteraemia and identify better treatment options for improved clinical outcomes. 相似文献
3.
Kaetzel CS 《Current biology : CB》2001,11(1):R35-R38
The polymeric immunoglobulin receptor (pIgR) is important in host defense, transporting antibodies across mucosal epithelial cells. Recent work has shown that, using a protein that binds directly to the pIgR, Streptococcus pneumoniae can co-opt the transcytosis machinery and gain entry into airway epithelial cells. 相似文献
4.
O. Hoegh-Guldberg 《Coral reefs (Online)》2009,28(3):569-575
Maynard et al. (Coral Reefs 27:745–749, 2008a) claim that much of the concern about the impacts of climate change on coral reefs has been “based on essentially untested
assumptions regarding reefs and their capacity to cope with future climate change”. If correct, this claim has important implications
for whether or not climate change represents the largest long-term threat to the sustainability of coral reefs, especially
given their ad hominem argument that many coral reef scientists are guilty of “popularising worst-case scenarios” at the expense
of truth. This article looks critically at the claims made by Maynard et al. (Coral Reefs 27:745–749, 2008a) and comes to a very different conclusion, with the thrust and veracity of their argument being called into question. Contrary
to the fears of Grigg (Coral Reefs 11:183–186, 1992), who originally made reference to the Cassandra syndrome due to his concern about the sensationalisation of science, the
proposition that coral reefs face enormous challenges from climate change and ocean acidification has and is being established
through “careful experimentation, long-term monitoring and objective interpretation”. While this is reassuring, coral reef
ecosystems continue to face major challenges from ocean warming and acidification. Given this, it is an imperative that scientists
continue to maintain the rigour of their research and to communicate their conclusions as widely and clearly as possible.
Given the shortage of time and the magnitude of the problem, there is little time to spare. 相似文献
5.
Macrophages are infected early during HIV infection and are thought to play the role of a Trojan horse by spreading infection in tissues. Most recent studies point out to a more complex role for macrophages in HIV infection: macrophages could contribute to both host defense and viral persistence and pathogenesis. Infected macrophages are a reservoir for HIV and modulate apoptosis of T cells present in their vicinity. Also, a functional impairment of HIV-infected macrophages may play a role in AIDS pathogenesis. Nevertheless, both activation and differentiation of monocyte/macrophages can interfere with susceptibility of these cells to infection. Therefore, a wide variety of stimuli result in HIV suppression through macrophage activation. At present times, a dynamic view on the role of macrophages in HIV infection arises which indicates that macrophages are a target for the virus and at the same time regulate its replication. Therefore, macrophages are at the cross-road between protection and pathogenesis in HIV infection due to their involvement both as a viral target and a key modulator of non-specific and specific immune responses. Future studies will help unravel the cellular and molecular mechanisms that underlie HIV-macrophage interactions and might result in new vaccine and/or therapeutic strategies. 相似文献
6.
Ute Möllmann Lothar Heinisch Adolf Bauernfeind Thilo Köhler Dorothe Ankel-Fuchs 《Biometals》2009,22(4):615-624
The outer membrane permeability barrier is an important resistance factor of bacterial pathogens. In combination with drug
inactivating enzymes, target alteration and efflux, it can increase resistance dramatically. A strategy to overcome this membrane-mediated
resistance is the misuse of bacterial transport systems. Most promising are those for iron transport. They are vital for virulence
and survival of bacteria in the infected host, where iron depletion is a defense mechanism against invading pathogens. We
synthesized biomimetic siderophores as shuttle vectors for active transport of antibiotics through the bacterial membrane.
Structure activity relationship studies resulted in siderophore aminopenicillin conjugates that were highly active against
Gram-negative pathogens which play a crucial role in destructive lung infections in cystic fibrosis patients and in severe
nosocomial infections. The mechanism of action and the uptake of the compounds via specific iron siderophore transport routes
were demonstrated. The novel conjugates were active against systemic Pseudomonas aeruginosa infections in mice with ED50 values comparable to the quinolone ofloxacin and show low toxicity. 相似文献
7.
Levon Halabelian Stefano Ricagno Sofia Giorgetti Carlo Santambrogio Alberto Barbiroli Sara Pellegrino Adnane Achour Rita Grandori Loredana Marchese Sara Raimondi P. Patrizia Mangione Gennaro Esposito Raya Al-Shawi J. Paul Simons Ivana Speck Monica Stoppini Martino Bolognesi Vittorio Bellotti 《The Journal of biological chemistry》2014,289(6):3318-3327
To form extracellular aggregates, amyloidogenic proteins bypass the intracellular quality control, which normally targets unfolded/aggregated polypeptides. Human D76N β2-microglobulin (β2m) variant is the prototype of unstable and amyloidogenic protein that forms abundant extracellular fibrillar deposits. Here we focus on the role of the class I major histocompatibility complex (MHCI) in the intracellular stabilization of D76N β2m. Using biophysical and structural approaches, we show that the MHCI containing D76N β2m (MHCI76) displays stability, dissociation patterns, and crystal structure comparable with those of the MHCI with wild type β2m. Conversely, limited proteolysis experiments show a reduced protease susceptibility for D76N β2m within the MHCI76 as compared with the free variant, suggesting that the MHCI has a chaperone-like activity in preventing D76N β2m degradation within the cell. Accordingly, D76N β2m is normally assembled in the MHCI and circulates as free plasma species in a transgenic mouse model. 相似文献
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10.
Marco A. Molina-Montenegro Gabriel I. Ballesteros Ian S. Acuña-Rodríguez Luis R. Pertierra Michelle Greve David M. Richardson Peter Convey Elisabeth M. Biersma William P. Goodall-Copestake Kevin K. Newsham 《Diversity & distributions》2023,29(11):1432-1444
Aim
Poa annua L. (annual bluegrass) is presently the sole invasive vascular plant species to have successfully established in Maritime Antarctica, where it poses a significant conservation threat to native plant species. However, the reasons for its success in the region have yet to be established. Here, we determined whether the invasiveness of P. annua, and its competitiveness with the native Antarctic hairgrass Deschampsia antarctica, is influenced by symbioses formed with seed fungal endophytes, and whether plants derived from seeds from four global regions differ in their performance.Locations
Four regions (Maritime Antarctica, sub-Antarctica, South America and Europe).Methods
Endophyte frequency was measured in P. annua seeds collected from the four regions. The germination, survival, biomass accumulation, flowering and competitiveness with D. antarctica of P. annua plants grown from endophyte-uncolonised and uncolonised seeds was determined in the laboratory. The effects of endophytes on P. annua seed germination and survival and seedling osmoprotection were also assessed in the Maritime Antarctic natural environment using locally-sourced seeds.Results
Endophytes were at least twice as frequent in seeds from Maritime Antarctica than in those from other regions. A higher proportion of endophyte-colonized seeds germinated and survived than did uncolonised seeds, but only when they originated from Maritime Antarctica. Seed endophytes increased the competitiveness of P. annua with D. antarctica, but only for plants grown from Maritime Antarctic seeds. In the field, endophyte-colonized seeds from Maritime Antarctica germinated and survived more frequently than uncolonised seeds, and osmoprotection was higher in seedlings grown from colonized seed.Main Conclusions
The findings indicate beneficial effects of seed endophytes on invasion-related traits of P. annua, such as survival, germination success and flowering. Together with vegetative and reproductive traits facilitating the colonization process, the seed-fungal endophyte symbiosis can be invoked as an important factor explaining the invasiveness of P. annua in Maritime Antarctica. 相似文献11.
The recent rise in drug resistance found amongst community acquired infections has sparked renewed interest in developing
antimicrobial agents that target resistant organisms and limit the natural selection of immune variants. Recent discoveries
have shown that iron uptake systems in bacteria and fungi are suitable targets for developing such therapeutic agents. The
use of siderophore-drug conjugates as “Trojan Horse” drug delivery agents has attracted particular interest in this area.
This review will discuss efforts in our research group to study the salmycin class of “Trojan Horse” antibiotics. Inspired
by the natural design of the salmycins, a series of desferridanoxamine-antibiotic conjugates were synthesized and tested in
microbial growth inhibition assays. The results of these studies will be related to understanding the role of drug release
in siderophore-mediated drug delivery with implications for future siderophore-drug conjugate design. 相似文献