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Boone Fallon posted an update 3 days, 1 hour ago
On the molecular level it significantly inhibited the effector transcript RNA III. In vivo testing, using the murine skin abscess model, confirmed the ability of staquorsin to modulate S. aureus virulence by effectively controlling the infection. Twenty passages of S. aureus in the presence of 40 μM staquorsin have not resulted in loss of activity as evidenced by maintaining its ability to reduce hemolysin production and RNA III transcript levels. In conclusion, we hereby describe a novel anti-virulence compound inhibiting the S. aureus Agr-system and its associated virulence factors. It is active both in vitro and in vivo, and its frequent use does not lead to the development of resistance. These findings model staquorsin as a promising drug candidate to join the fierce battle against the formidable pathogen S. aureus.QPX7728 is a novel β-lactamase inhibitor (BLI) that belongs to a class of cyclic boronates. The first member of this class, vaborbactam, is a BLI in the recently approved Vabomere (meropenem-vaborbactam). In this paper we provide the overview of the biochemical, structural and microbiological studies that were recently conducted with QPX7728. We show that QPX7728 is an ultra-broad-spectrum β-lactamase inhibitor with the broadest spectrum of inhibition reported to date in a single BLI molecule; in addition to potent inhibition of clinically important serine β-lactamases, including Class A and D carbapenemases from Enterobacterales and notably, diverse Class D carbapenemases from Acinetobacter, it also inhibits many metallo β-lactamases. Importantly, it is minimally affected by general intrinsic resistance mechanisms such as efflux and porin mutations that impede entry of drugs into gram-negative bacteria. QPX7728 combinations with several intravenous (IV) β-lactam antibiotics shows broad coverage of Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa, including strains that are resistant to other IV β-lactam-BLI combinations, e.g., ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam and imipenem-relebactam that were recently approved for clinical use. Based on studies with P. aeruginosa, different partner β-lactams in combination with QPX7728 may be optimal for the coverage of susceptible organisms. This provides microbiological justification for a stand-alone BLI product for co-administration with different β-lactams. QPX7728 can also be delivered orally; thus, its ultra-broad β-lactamase inhibition spectrum and other features could be also applied to oral QPX7728-based combination products. Clinical development of QPX7728 has been initiated.The use of probiotics and antifungal capabilities of the lactic acid bacteria (LAB) isolated from different niches is a strategy to prepare functional cultures and biopreservatives for food/feed industries. In the present study, LAB strains isolated from an Indian traditional fermented food, Pozha, were evaluated for their probiotic properties and biocontrol potential. A total of 20 LAB isolates were selected from Pozha samples collected aseptically and screened for their antagonistic activity against Fusarium verticillioides. Among the bioactive isolates, Lacticaseibacillus brevis MYSN105 showed the highest antifungal activity in vitro, causing some morphological alterations such as damaged mycelia and deformed conidia. Cell-free supernatant (CFS) from L. brevis MYSN105 at 16% concentration effectively reduced the mycelial biomass to 0.369 g compared to 1.938 g in control. Likewise, the conidial germination was inhibited to 20.12%, and the seed treatment using CFS induced a reduction of spore count to 4.1 × 106 spores/ml compared to 1.1 × 109 spores/ml for untreated seeds. selleck chemicals llc The internal transcribed spacer (ITS) copy number of F. verticillioides decreased to 5.73 × 107 and 9.026 × 107 by L. brevis MYSN105 and CFS treatment, respectively, compared to 8.94 × 1010 in control. The L. brevis MYSN105 showed high tolerance to in vitro gastrointestinal conditions and exhibited high adhesive abilities to intestinal epithelial cell lines. The comparative genome analysis demonstrated specific secondary metabolite region coding for bacteriocin and T3PKS (type III polyketide synthase) possibly related to survival and antimicrobial activity in the gut environment. Our results suggest that L. brevis MYSN105 has promising probiotic features and could be potentially used for developing biological control formulations to minimize F. verticillioides contamination and improve food safety measures.Tunicothrix halophila n. sp. was discovered in a hypersaline marine sample from Jeju Island, Korea. It is characterized by the highly reduced number of dorsal bristles. In addition, the main character of the genus Tunicothrix (e.g., alveolar layer) is absent/indistinct. To figure out its identity and phylogenetic relationship, we examined the new species based on modern morphological methods and molecular phylogenetic analyses. Since the parabirojimids are of basal position to core hypotrichs and a smaller data set could show incorrect phylogenetic relationships among the hypotrichs, we used a huge data set composed of 1,460 DNA sequences to infer the phylogenetic tree. The reduction of dorsal bristles is very likely a secondarily evolved character in hypotrichs, resulting in the independent phenotypic adaptation in the hypersaline ecosystems as shown in other hypersaline hypotrichs. Furthermore, the so-called right marginal row 1 in other congeners is found to produce a pretransverse and transverse cirrus and thus we recommend using the term frontoventral row. Based on our data, we can justify Tunicothrix halophila n. sp. as a new species; however, despite the phenotypic distinctiveness, we refrain to establish a new genus because of the missing data and the non-monophyly of Tunicothrix.The light-harvesting chlorophyll a/b complex protein 3 (LHCB3) of photosystem II plays important roles distributing the excitation energy and modulating the rate of state transition and stomatal response to abscisic acid. However, the functions of LHCB3 in plant immunity have not been well investigated. Here, we show that the expression of LHCB3 in Nicotiana benthamiana (NbLHCB3) was down-regulated by turnip mosaic virus (TuMV) infection. When NbLHCB3 was silenced by tobacco rattle virus-induced gene silencing, systemic infection of TuMV was inhibited. H2O2 was over-accumulated in NbLHCB3-silenced plants. Chemical treatment to inhibit or eliminate reactive oxygen species (ROS) impaired the resistance of the NbLHCB3-silenced plants to TuMV infection. Co-silencing of NbLHCB3 with genes involved in ROS production compromised the resistance of plants to TuMV but co-silencing of NbLHCB3 with genes in the ROS scavenging pathway increased resistance to the virus. Transgenic plants overexpressing NbLHCB3 were more susceptible to TuMV.