Adhesion and host cell modulation: critical pathogenicity determinants of Bartonella henselae

Bartonella henselae, the agent of cat scratch disease and the vasculoproliferative disorders bacillary angiomatosis and peliosis hepatis, contains to date two groups of described pathogenicity factors: adhesins and type IV secretion systems. Bartonella adhesin A (BadA), the Trw system and possibly filamentous hemagglutinin act as promiscous or specific adhesins, whereas the virulence locus (Vir)B/VirD4 type IV secretion system modulates a variety of host cell functions. BadA mediates bacterial adherence to endothelial cells and extracellular matrix proteins and triggers the induction of angiogenic gene programming. The VirB/VirD4 type IV secretion system is responsible for, e.g., inhibition of host cell apoptosis, bacterial persistence in erythrocytes, and endothelial sprouting. The Trw-conjugation system of Bartonella spp. mediates host-specific adherence to erythrocytes. Filamentous hemagglutinins represent additional potential pathogenicity factors which are not yet characterized. The exact molecular functions of these pathogenicity factors and their contribution to an orchestral interplay need to be analyzed to understand B. henselae pathogenicity in detail

Atom transfer radical additions with the cationic half-sandwich complex [Cp*Ru(PPh3)(2)(CH3CN)]OTf

The cationic ruthenium half-sandwich complex [Cp*Ru(PPh3)(2)(CH3CN)][OTf] (2) (CP* = eta(5)-C5Me5, OTf = SO3CF3) was synthesized by reduction of [Cp*RuCl2](2) with zinc in the presence of NaOTf and subsequent reaction with PPh3. When NaOTf was omitted, the corresponding tetrachlorozincate salts were obtained. Complex 2, as well as the salts [Cp*Ru(CH3CN)(3)](2)[ZnCl4] (3) and [Cp*Ru(PPh3)(2)(-)(CH3CN)](2)[ZnCl4] (4), were characterized by single-crystal X-ray analysis. Complex 2 proved to be a potent catalyst for the atom transfer radical addition of CCl4 and CHCl3 to terminal olefins, displaying a performance superior to that of the previously described neutral catalyst [Cp*RuCI(PPh3)(2)]. For the addition of CHCl3 to styrene, a total turnover number of 890 was achieved. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Synthesis, Structure and Reactivity of Homo- and Heterobimetallic Complexes of the General Formula [Cp*Ru(m-Cl)3ML] (LM = (arene)Ru, Cp*Rh, Cp*Ir)

The homo- and heterobimetallic complexes [Cp*Ru(m-Cl)3-ML] [LM = (C6H6)Ru, (cymene)Ru, (1,3,5-C6H3iPr3)Ru, Cp*Rh, Cp*Ir] were prepd. by reaction of [Cp*Ru(m-OMe)]2 with Me3SiCl and subsequent addn. of [LMCl2]2. The complexes [Cp*Ru(m-Cl)3Ru(cymene)] and [Cp*Ru(m-Cl)3-IrCp*] were characterized by single-crystal X-ray analyses. In crossover expts. with [Cp*Rh(m-Cl)3RuCl(PPh3)2] and [Cp*Ru(m-Cl)3Ru(1,3,5-C6H3iPr3)] in CD2Cl2, a dynamic equil. with the complexes [Cp*Rh(m-Cl)3RuCp*] and [(1,3,5-C6H3iPr3)Ru(m-Cl)3RuCl(PPh3) 2] was rapidly established, demonstrating the kinetic lability of the triple chloro bridge. Upon reaction of [Cp*Rh(m-Cl)3RuCp*] with benzene, the ionic complex [Cp*Ru(C6H6)][Cp*RhCl3] was formed, which was characterized by X-ray crystallog

Syntheses and structures of homo- and heterobimetallic, chloro-bridged complexes containing the RuCl3(AsPh3)(n) fragment (n=1,2)

The reaction of [RuCl3(AsPh3)(2)(MeOH)] with the dimeric complexes [(cod)RhCl](2), [(ppy)RhCl](2) (ppy = cyclometalated 2-phenylpyridine), [(cymene)RuCl2](2) and [CP*MCl2](2) (M = Rh, Ir) has been investigated. The structure of the resulting products was shown to depend on the reaction partner. Whereas for the rhodium complexes [(cod)RhCl](2) and [(ppy)RhCl](2), heterobimetallic compounds with two halogeno-bridges were found, the reactions with the halfsandwich complexes [(cymene)RuCl2](2) and [CP*MCl2](2) gave triply bridged products with concomitant formation of mononuclear [(pi-ligand)MCl2(AsPh3)] side products. The new complexes were all characterized by single crystal X-ray analysis. (C) 2004 Elsevier B.V. All rights reserved

Combinatorial synthesis of bimetallic complexes with three halogeno bridges

Methods for the synthesis of bimetallic complexes in which two different metal fragments are connected by three chloro or bromo bridges are reported. The reactions are general, fast, and give rise to structurally defined products in quantitative yields. Therefore, they are ideally suited for generating a library of homo- and heterobimetallic complexes in a combinatorial fashion. This is of special interest for applications in homogeneous catalysis. Selected members of this library were synthesized and comprehensively characterized; single-crystal X-ray analyses were performed for 15 new bimetallic compounds

Combinatorial synthesis of bimetallic complexes with three halogeno bridges

Methods for the synthesis of bimetallic complexes in which two different metal fragments are connected by three chloro or bromo bridges are reported. The reactions are general, fast, and give rise to structurally defined products in quantitative yields. Therefore, they are ideally suited for generating a library of homo- and heterobimetallic complexes in a combinatorial fashion. This is of special interest for applications in homogeneous catalysis. Selected members of this library were synthesized and comprehensively characterized; single-crystal X-ray analyses were performed for 15 new bimetallic compounds

Study of drug particle distributions within mini-tablets using synchrotron X-ray microtomography and superpixel image clustering

Uniform drug distribution within fast disintegrating tablets is a key quality measure to ensure a reliable, steady, and targeted release of the contained active pharmaceutical ingredients. In this work, the drug particle distribution in mini-tablets was studied with synchrotron phase contrast X-ray microtomography. Mini-tablets had a weight of 9.5 mg and a drug load from 2.5% to 20%. Moxidectin, a drug used for treatment of parasitic infections, was used as a model compound. Drug content covered a range from 91% to 121% of the target dose. A linear iterative clustering (SLIC) superpixel method was used for segmentation, analysis, and visualization of the spatial distribution of individual tablet components (i.e., pores, excipients, and drug). Results show that the drug was not uniformly distributed within the tablet, revealing an increasing drug load towards the tablets' outer boundaries and thus indicative of a radial displacement of drug particles during compaction. The presented method can be used for the quantitative analysis of drug content and drug distribution within pharmaceutical tablets, allowing for the optimization of fast disintegrating formulations. The results also affirm that that drug loads up to 20% will not lead to segregation for moxidectin

The BatR/BatS Two-Component Regulatory System Controls the Adaptive Response of Bartonella henselae during Human Endothelial Cell Infection ▿ † ‡

Here, we report the first comprehensive study of Bartonella henselae gene expression during infection of human endothelial cells. Expression of the main cluster of upregulated genes, comprising the VirB type IV secretion system and its secreted protein substrates, is shown to be under the positive control of the transcriptional regulator BatR. We demonstrate binding of BatR to the promoters of the virB operon and a substrate-encoding gene and provide biochemical evidence that BatR and BatS constitute a functional two-component regulatory system. Moreover, in contrast to the acid-inducible (pH 5.5) homologs ChvG/ChvI of Agrobacterium tumefaciens, BatR/BatS are optimally activated at the physiological pH of blood (pH 7.4). By conservation analysis of the BatR regulon, we show that BatR/BatS are uniquely adapted to upregulate a genus-specific virulence regulon during hemotropic infection in mammals. Thus, we propose that BatR/BatS two-component system homologs represent vertically inherited pH sensors that control the expression of horizontally transmitted gene sets critical for the diverse host-associated life styles of the alphaproteobacteria