Tris{2-[(3-thien­yl)methyl­idene­amino]­eth­yl}amine

The title compound, C21H24N4S3, is a tripodal Schiff base that was obtained from the reaction of tris­(2-amino­eth­yl)amine (tren) and thio­phene-3-carbaldehyde. The compound forms a cavity with approximate C3 symmetry. One of the thio­phene units is disordered in a 0.764 (2):0.236 (2) ratio. In the crystal, the three thio­phene ligands are involved in intra­molecular C—H⋯π inter­actions and the mol­ecules are connected by C—H⋯N inter­actions, forming hydrogen-bonded chains

Sideromycins: tools and antibiotics

Sideromycins are antibiotics covalently linked to siderophores. They are actively transported into gram-positive and gram-negative bacteria. Energy-coupled transport across the outer membrane and the cytoplasmic membrane strongly increases their antibiotic efficiency; their minimal inhibitory concentration is at least 100-fold lower than that of antibiotics that enter cells by diffusion. This is particularly relevant for gram-negative bacteria because the outer membrane, which usually forms a permeability barrier, in this case actively contributes to the uptake of sideromycins. Sideromycin-resistant mutants can be used to identify siderophore transport systems since the mutations are usually in transport genes. Two sideromycins, albomycin and salmycin, are discussed here. Albomycin, a derivative of ferrichrome with a bound thioribosyl-pyrimidine moiety, inhibts seryl-t-RNA synthetase. Salmycin, a ferrioxamine derivative with a bound aminodisaccharide, presumably inhibts protein synthesis. Crystal structures of albomycin bound to the outer membrane transporter FhuA and the periplasmic binding protein FhuD have been determined. Albomycin and salmycin have been used to characterize the transport systems of Escherichia coli and Streptococcus pneumoniae and of Staphylococcus aureus, respectively. The in vivo efficacy of albomycin and salmycin has been examined in a mouse model using Yersinia enterocolitica, S. pneumoniae, and S. aureus infections. Albomycin is effective in clearing infections, whereas salmycin is too unstable to lead to a large reduction in bacterial numbers. The recovery rate of albomycin-resistant mutants is lower than that of the wild-type, which suggests a reduced fitness of the mutants. Albomycin could be a useful antibiotic provided sufficient quantities can be isolated from streptomycetes or synthesized chemically

3,3′-Bis(quinolin-8-yl)-1,1′-[4,4′-methyl­enebis(4,1-phenyl­ene)]diurea

The title compound, C33H26N6O2, contains two 3-(quinolin-8-yl)urea groups linked to a diphenyl­methane. The asymmetric unit contains two mol­ecules, A and B. Each quinoline plane is essentially parallel to the attached urea unit [dihedral angles = 8.97 (18) and 8.81 (19) in molecule A and 18.47 (18) and 4.09 (19)° in molecule B]. The two benzene rings are twisted, making dihedral angles of 81.36 (8)° in A and 87.20 (9)° in B. The molecular structures are stabilized by intramolecular N—H⋯N hydrogen bonds. In the crystal, each urea O atom is involved in two N—H⋯O hydrogen bonds, generating two inter­penetrating three-dimensional sets of mol­ecules

Aktivitätsspektrum und in-vivo Aktivität von Albomycin und dessen Nutzung zur Aufklärung des Hydroxamattransportsystems von Streptococcus pneumoniae

Albomycin overproduction was standardized and mid-scale fermentation was carried out. From the fermentation broth albomycin was recovered to homogeneity by three-step chromatography. This purified albomycin was used throughout this study. The activity spectrum of albomycin against common bacterial pathogens was determined. Correlation of ferrichrome utilization and albomycin sensitivity was verified. Intrinsic albomycin resistance of Proteus and Morganella attributed to the lack of a ferrichrome transport system, unlike other enterobacteriaceae tested. Pseudomonads and Haemophilus related generas were also intrinsically resistant. Among gram positives, coagulase positive staphylococci, Bacillus subtilis and pneumococci were highly sensitive to albomycin. Reasons of pneumococcal sensitivity to albomycin and salmycin were determined. Competitive cross-feeding of sideromycins with hydroxamate siderophores and proteolytic cleavage experiments provided evidence that albomycin is transported in pneumococci through a hydroxamate transport system. Targeted mutagenesis ( by Insertion and Deletion) were done to identify the involvement of the putative iron transport systems in the R6 strain. This approach identified the gene for the FhuD binding protein of the transport system. Complementation by ectopic insertion confirmed the role of fhuD in hydroxamate transport in pneumococcus. To identify the other components of the hydroxamate transport machinery, an in vitro random mutagenesis method was standardized. From a randomly mutagenized library transport negative mutants were picked. From these mutants the fhuB and the fhuG genes were identified. Recombinant FhuD was cloned and overexpressed. This FhuD is a lipoprotein that is able to bind a wide variety of hydroxamate substrates but not free Fe2+/3+ or haemin. Substrate binding leads to conformational changes conferring partial resistance to proteolytic attack. A 3D homology model of Sp-FhuD was made based on E. coli FhuD crystal structure. 3D alignment identified both similarity and minor variations at the substrate binding pocket. Other than in vitro, efficacy of albomycin was tested in a murine infection model. After 6 h of single dose antibiotic administration, albomycin performed better than equivalent dose of gentamycin to reduce bacterial load in Y. enterocolitica infected mice spleen. Albomycin was highly effective against murine pneumococcal infections. All albomycin treated mice recovered from pneumococcal infection. In a mixed infection model albomycin resistant mutants showed a compromised virulence.In dieser Arbeit wurde die Überproduktion von Albomycin standardisiert und eine Fermentation im mittleren Maßstab durchgeführt. Das Albomycin wurde über dreistufige Chromatographie aus dem Kulturfiltrat gewonnen und aufgereinigt. Das auf diese Weise gereinigte Albomycin wurde für diese Studie verwendet. Desweiteren wurde das Tätigkeitsspektrum von Albomycin gegen allgemeine bakterielle Krankheitserreger festgestellt. Eine Korrelation von Ferrichromaufnahme und damit einhergehender Albomycinempfindlichkeit wurde überprüft. Die vorhandene Albomycinresistenz von Proteus und Morganella, wurde anders als bei den übrigen geprüften Enterobacteriaceae, auf das Fehlen eines Ferrichromtransportsystem zurückgeführt. Pseudomonaden und Haemophilus-Arten zeigten dagegen eine intrinsische Resistenz. Unter Grampositiven waren Koagulase-positive Staphylokokken, Bacillus subtilis und Pneumococci in hohem Grade empfindlich gegenüber Albomycin. Die Gründe für die Empfindlichkeit der Pneumokokken gegenüber Albomycin und Salmycin wurden näher untersucht. Versuche zur kompetitiven Verdrängung von Hydroxamtasiderophoren durch Sideromycine, sowie proteolytische Spaltung von Albomycin lieferten Beweis, daß Albomycin von Pneumokokken über das Hydroxamattransportsystem aufgenommen wird. Im Stamm Streptococcus pneumoniae R6 wurde eine zielgerichtete Mutagenese (Insertion und anschliessende Deletion) durchgeführt, um die für die Albomycinaufnahme verantwortlichen, mutmaßlichen Eisentransportsysteme zu kennzeichnen. Hier konnte gezeigt werden, daß das Gen FhuD eine Schlüsselrolle im Transport einnimmt. Die Komplementierung des entsprechenden Gens bestätigte die Rolle von fhuD für den Hydroxamattransport bei Pneumokokken. Um die übrigen Komponenten des Hydroxamattransportsystems zu identifizieren, wurde eine randomisierte in vitro- Mutagenese durchgeführt. Aus der erhaltenen DNA-Bibliothek wurden entsprechende Mutanten gepickt und die Gene fhuB und fhuG identifiziert. Zudem wurde ein rekombinantes FhuD kloniert und überexprimiert. FhuD ist ein Lipoprotein mit der Fähigkeit, eine Reihe von Hydroxamte als Substrat, jedoch kein freies Eisen oder Häm, zu binden. Die Substratbindung hat eine Konformationsänderung zur Folge, die zu einer teilweisen Resistenz gegen einen proteolytischen Verdau führt. Aufgrund von Daten aus der Kristallstruktur des homologen FhuD von E.coli, wurde 3D-Modell für das FhuD von S. pneumoniae entwickelt. Ein 3D-Alignment konnte sowohl Ähnlichkeiten als auch kleiner Variationen im Bereich der Substratbindestelle identifizieren. In einem weiteren Teil wurde die in vivo-Aktivität von Albomycin am Maus-Infektionsmodell untersucht. In mit Yersinia enterocolitica infizierten Mäusen, zeigte sich Albomycin als Einzeldosis nach sechs Stunden wirksamer als eine äquivalente Dosis Gentamycin hinsichtlich der Reduzierung der Bakterienzahl. Albomycn erwies sich im Maus-Modell außerdem als hocheffektiv gegenüber Infektionen mit S. pneumoniae. Hier erholten sich alle mit Albomycin behandelten Mäuse von der Pneumokokken-Infektion. Im gemischten Infektionsmodell zeigten Albomycin-resistente Stämme eine abgeschwächte Virulenz

Shifting seasonality of cyclones and western boundary current interactions in Bay of Bengal as observed during Amphan and Fani

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Sil, S., Gangopadhyay, A., Gawarkiewicz, G., & Pramanik, S. Shifting seasonality of cyclones and western boundary current interactions in Bay of Bengal as observed during Amphan and Fani. Scientific Reports, 11(1), (2021): 22052 https://doi.org/10.1038/s41598-021-01607-6.In recent years, the seasonal patterns of Tropical Cyclones (TC) in the Bay of Bengal have been shifting. While tropical depressions have been common in March–May (spring), they typically have been relatively weaker than the TCs during October–December. Here we show that the spatial pattern of recent warming trends during the last two decades in the southwestern Bay has allowed for stronger springtime pre-monsoon cyclones such as Amphan (May 2020, Super Cyclone) and Fani (April–May 2019, Extremely Severe Cyclone). The tracks of the pre-monsoon cyclones shifted westward, concurrent with an increasing rate of warming. This shift allowed both Fani and Amphan tracks to cross the northeastward warm Western Boundary Current (WBC) and associated warm anti-cyclonic eddies, while the weaker Viyaru (April 2013, Cyclonic Storm) did not interact with the WBC. A quantitative model linking the available along-track heat potential to cyclone’s intensity is developed to understand the impact of the WBC on cyclone intensification. The influence of the warming WBC and associated anti-cyclonic eddies will likely result in much stronger springtime TCs becoming relatively common in the future.The authors gratefully acknowledge the financial and infrastructural support from the Indian Institute of Technology Bhubaneswar to carry out this research. SS acknowledges the financial assistance from Science and Engineering Research Board (SERB), Government of India (Grant No. CRG/2019/005842). All the figures are prepared using MATLAB. AG and SS appreciate the support of SERB's VAJRA Faculty Scheme (VJR/2018/000108) for the initiation of this collaborative work between SMAST and IITBBS. AG also acknowledges partial support from NSF (OCE 1851242) in completing this manuscript. GG was supported by a Grant from the Office of Naval Research as part of the Task Force Ocean initiative