Chemotherapy with Phage Lysins Reduces Pneumococcal Colonization of the Respiratory Tract.

Bacteriophage-borne lytic enzymes, also named lysins or enzybiotics, are efficient agents for the killing of bacterial pathogens. The colonization of the respiratory tract by is a prerequisite for the establishment of the infection process. Hence, we have evaluated the antibacterial activities of three different lysins against pneumococcal colonization using human nasopharyngeal and lung epithelial cells as well as a mouse model of nasopharyngeal colonization.

Membrane Microdomain Disassembly Inhibits MRSA Antibiotic Resistance.

A number of bacterial cell processes are confined functional membrane microdomains (FMMs), structurally and functionally similar to lipid rafts of eukaryotic cells. How bacteria organize these intricate platforms and what their biological significance is remain important questions. Using the pathogen methicillin-resistant Staphylococcus aureus (MRSA), we show here that membrane-carotenoid interaction with the scaffold protein flotillin leads to FMM formation, which can be visualized using super-resolution array tomography.

Molecular characterization of a new gene cluster for steroid degradation in Mycobacterium smegmatis.

The C-19 steroids 4-androstene-3,17-dione (AD), 1,4-androstadiene-3,17-dione (ADD) or 9α-hydroxy-4-androstene-3,17-dione (9OH-AD), which have been postulated as intermediates of the cholesterol catabolic pathway in Mycobacterium smegmatis, cannot be used as sole carbon and energy sources by this bacterium. Only the ΔkstR mutant which constitutively expresses the genes repressed by the KstR regulator can metabolize AD and ADD with severe difficulties but still cannot metabolize 9OH-AD, suggesting that these compounds are not true intermediates but side products of the cholesterol pathway. However, we have found that some M.

Mycobacterium smegmatis is a suitable cell factory for the production of steroidic synthons.

A number of pharmaceutical steroid synthons are currently produced through the microbial side-chain cleavage of natural sterols as an alternative to multi-step chemical synthesis. Industrially, these synthons have been usually produced through fermentative processes using environmental isolated microorganisms or their conventional mutants. Mycobacterium smegmatis mc 155 is a model organism for tuberculosis studies which uses cholesterol as the sole carbon and energy source for growth, as other mycobacterial strains.

Auranofin-loaded nanoparticles as a new therapeutic tool to fight streptococcal infections.

Drug-loaded nanoparticles (NPs) can improve infection treatment by ensuring drug concentration at the right place within the therapeutic window. Poly(lactic-co-glycolic acid) (PLGA) NPs are able to enhance drug localization in target site and to sustainably release the entrapped molecule, reducing the secondary effects caused by systemic antibiotic administration. We have loaded auranofin, a gold compound traditionally used for treatment of rheumatoid arthritis, into PLGA NPs and their efficiency as antibacterial agent against two Gram-positive pathogens, Streptococcus pneumoniae and Streptococcus pyogenes was evaluated.

Aromatic Esters of Bicyclic Amines as Antimicrobials against Streptococcus pneumoniae.

A double approach was followed in the search of novel inhibitors of the surface choline-binding proteins (CBPs) of Streptococcus pneumoniae (pneumococcus) with antimicrobial properties. First, a library of 49 rationally-designed esters of alkyl amines was screened for their specific binding to CBPs. The best binders, being esters of bicyclic amines (EBAs), were then tested for their in vitro effect on pneumococcal growth and morphology.

A novel chimeric phage lysin with high in vitro and in vivo bactericidal activity against Streptococcus pneumoniae.

Objectives: Streptococcus pneumoniae is becoming increasingly antibiotic resistant worldwide and new antimicrobials are urgently needed. Our aim was new chimeric phage endolysins, or lysins, with improved bactericidal activity by swapping the structural components of two pneumococcal phage lysozymes: Cpl-1 (the best lysin tested to date) and Cpl-7S.

Methods: The bactericidal effects of four new chimeric lysins were checked against several bacteria.

Deciphering the transcriptional regulation of cholesterol catabolic pathway in mycobacteria: identification of the inducer of KstR repressor.

Cholesterol degradation plays a prominent role in Mycobacterium tuberculosis infection; therefore, to develop new tools to combat this disease, we need to decipher the components comprising and regulating the corresponding pathway. A TetR-like repressor (KstR) regulates the upper part of this complex catabolic pathway, but the induction mechanism remains unknown. Using a biophysical approach, we have discovered that the inducer molecule of KstR in M.

Tuneable reactivity with PPh3 and SnX2 of four- and five-coordinate Pd(II) and Pt(II) complexes containing polyphosphines.

The reactivity of the unusual d(8) trigonal-bipyramidal systems [MX(PP3)]X (X = Cl: M = Pd(1a), Pt(2a); X = Br: M = Pd(3a), Pt(4a); X = I: M = Pd(5a), Pt(6a); PP3 = tris[2-(diphenylphosphino)ethyl]phosphine) in CHCl3-CH3OH, the square-pyramidal compounds [MCl(NP3)]Cl (M = Pd(7a); Pt(8a); NP3 = tris[2-(diphenylphosphino)ethyl]amine) in CD3OD-DMF and the distorted square-planar mononuclear [MX(PNP)]X (M = Pd: X = Cl(10a); M = Pt: X = I(10b); PNP = bis[2-(diphenylphosphino)ethyl]amine) and the heteronuclear [PdAu2X4(PP3)] [X = I(9a), Cl(14a), Br(15a)] and [MAuX2(PP3)]X [M = Pd: X = Cl(16a); M = Pt: X = Cl(17a), Br(18a)] species in CDCl3 with PPh3 + SnX2 has been explored to establish the factors that influence the nature of the products. With the mononuclear precursors the course of the reaction is strongly dependent on the tripodal or linear arrangement of the polydentate ligand and in the former case on the halogen. Thus, while for chlorides (1a-2a, 7a-8a) and bromides (3a-4a) the reaction led to the trigonal-bipyramidal compounds [M(SnCl3)(AP3)][SnCl3] [A = P: M = Pd(1), Pt(2); A = N: M = Pd(7), Pt(8)], [MBr(PP3)][SnBr3] [M = Pd(4), Pt(6)] containing M-Sn and M-Br bonds, respectively, for iodides (5a-6a) resulted in the unknown neutral square-planar compounds [MI2(PP(PO)2)(SnI2)2] [M = Pd(9) and Pt(10)] bearing two dangling P=O-SnI2 units and P2MI2 environments.

A highly conserved mycobacterial cholesterol catabolic pathway.

Degradation of the cholesterol side-chain in Mycobacterium tuberculosis is initiated by two cytochromes P450, CYP125A1 and CYP142A1, that sequentially oxidize C26 to the alcohol, aldehyde and acid metabolites. Here we report characterization of the homologous enzymes CYP125A3 and CYP142A2 from Mycobacterium smegmatis mc(2) 155. Heterologously expressed, purified CYP125A3 and CYP142A2 bound cholesterol, 4-cholesten-3-one, and antifungal azole drugs.

ChoG is the main inducible extracellular cholesterol oxidase of Rhodococcus sp. strain CECT3014.

Cholesterol catabolism has been reported in different bacteria and particularly in several Rhodococcus species, but the genetic of this complex pathway is not yet very well defined. In this work we report the isolation and sequencing of a 9.8 kb DNA fragment of Rhodococcus sp.

Tripodal polyphosphine ligands as inductors of chelate ring-opening processes in mononuclear palladium(II) and platinum(II) compounds. The X-ray crystal structure of two derivatives containing dangling phosphorus.

The reaction of NP(3) (tris[2-(diphenylphosphino)ethyl]amine and PP(3) (tris[2-(diphenylphosphino)ethyl]phosphine) with the five-coordinate complexes [PdCl(NP(3))]Cl (1) and [MX(PP(3))]X [M = Pd: X = Cl(2), Br(3), I(4); M = Pt: X = Cl(5), Br(6), I(7)], respectively, followed by (31)P{(1)H}NMR when X = Cl, led to the formation of unprecedented four-coordinate halides in a 1 : 2 metal to ligand ratio, [M(AP(3))(2)]X(2) [A = N, M = Pd: X = Cl(8); A = P, M = Pd: X = Cl(9), Br(10), I(11); A = P, M = Pt: X = Cl(12), Br(13), I (14)], containing reactive dangling phosphorus. Given the non characterised precursors [M(ONO(2))(PP(3))](NO(3))], the interaction between the heteronuclear species [MAg(NO(3))(3)(PP(3))] [M = Pd(15), Pt(16)] and PP(3) was explored. It was found that the addition of 1 equivalent of phosphine afforded [MAg(NO(3))(PP(3))(2)](NO(3))(2) [M = Pd(15*), Pt(16*)] containing Ag(I) bound to two dangling phosphorus while the reaction with 2 equivalents led to the complexes [M(PP(3))(2)](NO(3))(2) [M = Pd (17), Pt (18)] in coexistence with [Ag(2)(mu-PP(3))(2)](NO(3))(2).

Morphological, physiological, and molecular characterization of a newly isolated steroid-degrading actinomycete, identified as rhodococcus ruber strain Chol-4.

The aerobic degradation of cholesterol, testosterone, androsterone, progesterone, and further steroid compounds as sole carbon source has been observed in the newly isolated bacterial Gram-positive strain Chol-4. The 16S rRNA gene sequence shares the greatest similarity with members of the genus Rhodococcus, with the closest shared nucleotide identities of 98-99% with Rhodococcus ruber (DSM 43338(T)) and Rhodococcus aetherivorans (DSM 44752(T)). Phylogenetic analysis of Rhodococcus 16S rRNA gene sequences consistently places strain Chol-4 in a clade shared with those both type strains within the Rhodococcus rhodochrous subclade.

Gordonia cholesterolivorans sp. nov., a cholesterol-degrading actinomycete isolated from sewage sludge.

The taxonomic position of the cholesterol-degrading strain Chol-3(T), isolated from a sewage sludge sample, was clarified using a polyphasic taxonomic approach. Phylogenetic analysis of its 16S rRNA gene sequence, whole-cell fatty acid profile and mycolic acid composition revealed that this isolate is a member of the genus Gordonia with the species Gordonia sihwensis, G. hydrophobica and G.

Novel chelate ring-opening induced by silver(I) of five-coordinate palladium(II) and platinum(II) complexes containing tripodal polyphosphines.

The ionic complexes [Pd(NP 3)X]X [NP 3 = tris[2-(diphenylphosphino)ethyl]amine, X = Cl (1), Br(2)] and [M(PP 3)X]X [PP 3 = tris[2-(diphenylphosphino)ethyl]phosphine, M = Pd, X = Cl (3), Br(4); M = Pt, X = Cl (5), Br (6)] contain square pyramidal (1, 2) and trigonal bipyramidal (3- 6) cations with three fused chelate rings to M and one M-X bond. By addition of AgX salts (X = Cl, Br, NO 3) an unexpected ring-opening reaction occurs with formation of the heteronuclear species PdAg(NP 3)X 3 [X = Cl (7), Br (8)], MAg(PP 3)X 3 [M = Pd, X = Cl (9), Br (10), NO 3 (13);M = Pt, X = Cl (11), Br (12), NO 3 (14)]. The complexes have been characterized in the solid state and solution.

Preparation and structural characterization of ionic five-coordinate palladium(II) and platinum(II) complexes of the ligand tris[2-(diphenylphosphino)ethyl]phosphine. Insertion of SnCl(2) into M-Cl bonds (M = Pd, Pt) and hydroformylation activity of the Pt-SnCl(3) systems.

The five-coordinate palladium(II) and platinum(II) complexes [M(PP(3))Cl]Cl [M = Pd (1), Pt (2)] (PP(3) = tris[2-(diphenylphosphino)ethyl]phosphine) were prepared by interaction of aqueous solutions of MCl(4)(2-) salts with PP(3) in CHCl(3). Complexes 1 and 2 undergo facile chloro substitution reactions with KCN in 1:1 and 1:2 ratios to afford complexes [M(PP(3))(CN)]Cl [M = Pt (3)] and [M(PP(3))(CN)](CN) [M = Pd (4), Pt (5)] possessing M-C bonds, both in solution and in the solid state. The reaction of 1 and 2 with SnCl(2) in CDCl(3) occurs with insertion of SnCl(2) into M-Cl bonds leading to the formation of [M(PP(3))(SnCl(3))](SnCl(3)) [M = Pd (6), M = Pt (7)].