Notes

Will the story coronavirus make use of the ocular surface being an front door into the entire body or just as one an infection internet site?
Finally, we used isobologram analysis to compare combinations of the ELQs with either proguanil or atovaquone. We show that all quinolone combinations with proguanil are synergistic against P falciparum However, against P knowlesi, no evidence of synergy between proguanil and the quinolones was found. Importantly, combining the novel quinolone ELQ-300 with atovaquone, was synergistic against both species. Our data identify potentially important species differences in proguanil susceptibility and its interaction with quinolones, and support the ongoing development of novel quinolones as potent antimalarials that target multiple species. Copyright © 2020 American Society for Microbiology.Bacterial persisters are phenotypic variants that temporarily demonstrate an extraordinary tolerance toward antibiotics. Persisters have been linked to the recalcitrance of biofilm related infections; hence, a complete understanding of their physiology can lead to improvement of therapeutic strategies for such infections. Mechanisms pertaining to persister formation are thought to be associated with stress response pathways triggered by intra- or extra-cellular stress factors. Unfortunately, studies demonstrating the effects of osmolyte- and/or pH- induced stresses on bacterial persistence are largely missing. To fill this knowledge gap within the field, we studied the effects of various osmolytes and pH conditions on Escherichia coli persistence with the use of phenotype microarrays and antibiotic tolerance assays. Although we found that a number of chemicals and pH environments, including urea, sodium nitrite and acidic pH, significantly reduced persister formation in E. coli compared to no-osmolyte/no-buffer controls, this reduction in persister levels was less pronounced in late-stationary-phase cultures. Our results further demonstrated a positive correlation between cell growth and persister formation, which challenges the general notion in the field that slow-growing cultures have more persister cells than fast-growing cultures. Copyright © 2020 American Society for Microbiology.Lactoferrin (LF) is a multifunctional milk protein with antimicrobial activity against a range of pathogens. While numerous studies report that LF is active against fungi, there are considerable differences in the level of antifungal activity and the capacity of LF to interact with other drugs. Here we undertake a comprehensive evaluation of the antifungal spectrum of activity of three defined sources of LF across 22 yeast and 24 mould species, and assess interactions with six widely used antifungal drugs. LF was broadly and consistently active across all yeast species (MIC 8-64 μg/ml), with the extent of activity strongly affected by iron saturation. LF was synergistic with amphotericin B (AMB) in 19 out of 22 yeast species tested and synergy was unaffected by iron saturation but affected by the extent of LF digestion. LF+AMB combination therapy significantly prolonged the survival of Galleria mellonella infected with Candida albicans or Cryptococcus neoformans and decreased fungal burden 12-25 fold. Evidence that LF directly interacts with the fungal cell surface was seen via SEM, which showed pore formation, hyphal thinning and major cell collapse in response to LF+AMB synergy. Important virulence mechanisms were disrupted by LF+AMB treatment, which significantly prevented biofilms in C. albicans and C. glabrata, inhibited hyphal development in C. albicans, and reduced cell and capsule size and phenotypic diversity in Cryptococcus. Our results demonstrate the potential of LF+AMB as an antifungal treatment that is broadly synergistic against important yeast pathogens, with synergy attributed to the presence of one or more LF peptides. Copyright © 2020 Fernandes et al.Antiretroviral therapy (ART) suppresses HIV-1 replication, but fails to cure the infection. The presence of an extremely stable viral latent reservoir, primarily in resting memory CD4+ T cells, remains a major obstacle to viral eradication. "Shock and Kill" strategy targets these latently-infected cells and boosts immune recognition and clearance, which continues to be a promising approach for HIV-1 functional cure. Although some latency reversing agents (LRAs) have been reported, no apparent clinical progress has been made, so it is still vitally important to seek for novel and effective LRAs. Here we report that thiostrepton (TSR), a proteasome inhibitor, reactivates latent HIV-1 effectively in cellular models and in primary CD4+ T cells from ART-suppressed individuals ex vivo TSR does not induce global T cell activation, severe cytotoxicity or CD8+ T cell dysfunction, making it a prospective LRA candidate. We also observed a significant synergistic effect of reactivation when combining TSR with JQ1, prostratin or bryostatin-1. Interestingly, 6 TSR analogues also show similar or more effective reactivation abilities comparing to TSR. We further verified that TSR upregulated expression of heat shock proteins (HSPs) in CD4+ T cells, which subsequently activated positive transcriptional elongation factor b (p-TEFb) and NF-κB signals, leading to viral reactivation. In summary, we identify TSR as a novel LRA, which could bear important significance to applications for HIV-1 functional cure in the future. Copyright © 2020 American Society for Microbiology.Omadacycline is an aminomethylcycline antibiotic with in vitro activity against pathogens causing community-acquired bacterial pneumonia (CABP). This study investigated the activity of omadacycline against Legionella pneumophila strains isolated between 1995 and 2014 from nosocomial or community-acquired respiratory infections. Omadacycline exhibited extracellular activity similar to comparator antibiotics; intracellular penetrance was found by day 3 of omadacycline exposure. compound library inhibitor These results support the utility of omadacycline as an effective antibiotic for the treatment of CABP caused by L. pneumophila. Copyright © 2020 Dubois et al.Carbapenem-resistant Enterobacteriaceae (CRE) has become a public health threat worldwide.…. Copyright © 2020 American Society for Microbiology.
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