Imidazo[4,5-<Emphasis Type="Italic">a</Emphasis>]quinindolines as highly effective antibacterial agents

Resistance to antimicrobial agents is a concern that exists globally and has a considerable impact on human and animal health, so that the discovery of new antibacterial compounds has become increasingly more important in combating infectious disease. In this paper, imidazo[4,5-a]quinindolines are introduced as new antibacterial agents against Gram-positive and Gram-negative bacteria. These pentacyclic compounds are synthesized by the reaction of N-alkyl-5-nitrobenzimidazoles with 2-(1-alkyl-1H-3-indolyl)acetonitrile under basic conditions in excellent yields. The structures of newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectral data. The antibacterial activities of the synthesized compounds were screened against standard strains of two Gram-positive and two Gram-negative bacteria using the broth microdilution method. Most of the compounds studied showed promising activities against both types of bacteria.     

Formation of poly(3-hydroxyalkanoates) by phototrophic and chemolithotrophic bacteria

The formation of poly(3-hydroxyalkanoic acid), PHA, by various strains of chemolithotrophic and phototrophic bacteria has been examined. Chemolithotrophic bacteria were grown aerobically under nitrogen-limiting conditions on various aliphatic organic acids. Phototrophic bacteria were grown anaerobically in the light on a nitrogen-rich medium and were subsequently transferred to a nitrogen-free medium containing acetate, propionate, valerate, heptanoate or octanoate as carbon source. All 41 strains investigated in this study were able to synthesize and accumulate PHA. All 11 strains of chemolithotrophic bacteria and all 15 strains belonging to the non-sulfur purple bacteria synthesized a polymer, which contained 3-hydroxy-valerate (3HV) beside 3-hydroxybutyrate (3HB), if the cells were cultivated in the presence of propionate, valerate or heptanoate. Many non-sulfur purple bacteria synthesized copolyesters of 3HB and 3HV even with acetate as carbon source. In contrast, most sulfur purple bacteria did not incorporate 3HV at all. Among 15 strains tested, only Chromatium vinosum strain 1611, C. purpuratum strain BN5500 and Lamprocystis roseopersicina strain 3112 were able to synthesize polyesters containing 3HV with propionate, valerate or heptanoate as carbon source.     

细菌群体感应信号分子与抑制剂研究进展

具有群体感应系统的细菌通过相互交换一种自动诱导（autoinducer）信号分子来实现彼此问的信息交流。当信号分子积累到一定浓度时会改变细菌特定基因的表达,如生物膜的形成、生物发光行为、毒性基因的表达、孢子的形成等。近年来,人们发现了多种天然或者人工合成的群体感应抑制剂,可以干扰群感系统的信息回路。本文系统地阐述了细菌群体感应信息系统的划分、自体诱导分子及其抑制剂的研究进展。     

Dynamics of production of extracellular polysaccharides by nodule bacteria

The dynamics of the accumulation of the extracellular polysaccharides synthesized by nodule bacteria and the possibility of their assimilation by these bacteria as a source of carbon was studied. When nodule bacteria were cultured for 20 days in a medium containing glucose, an increase in the titer of the bacteria and the accumulation of extracellular polysaccharides was observed in the first three days. After this the titer of the nodule bacteria decreased with a decrease in the glucose in the medium, but the amount of extracellular polysaccharide synthesized did not increase. These data suggest that extracellular polysaccharides are not assimilated by nodule bacteria as a source of carbon and evidently are protective substances for the cells.     

Benzoxazinone — kanamycin derivative: a new fluorescent probe for flow cytometry analysis of bacteria (Agrobacterium tumefaciens)

Abstract A new polycation fluorescent dye (BVC-kinamycin-conjugate) has been synthesized and used to detect alive bacteria by flow cytometry. This fluorescent chromophore has the noteworthy property of being excited at the same wavelength as fluoresceinylated conjugates (488 nm) and to show a much longer emission wavelength (616 nm) than fluoresceinylated derivates (520 nm); furthermore its fluorescence intensity is not quenched at low pH in contrast with fluorescein. In such conditions, bacteria can easily be detected with cytofluorimeter equipped with a single excitation wavelength beam. The binding of fluoresceinylated lectins and antibodies onto a strain of Agrobacterium tumefaciens has been studied by this method.     

Role of temperate phage in bacterial dissociation

The analysis of literary and own data testifies that the dissociants may appear in bacteria population from spontaneous mutations and transfer of genetic material (conjugation, transformation, transduction). The phage conversion and different DNA reorganizations within a cell where prophage plays an active role, probably introduce the largest contribution into the dissociative transitions of variants which occur with high frequency (about 10(-2)-10(-4). The dissociation of various bacteria has been studied with different degree. The role of temperate phage has been shown in splitting of bacteria into variants in the genera Mycobacterium, Corynebacterium, some Bacillus, Clostridium, Staphylococcus, some enterobacteria, Yersinia, Vibrio Pseudomonas, Rhizobium, Nostoc; the participation of prophage in dissociation of bacteria of the genera Xanthomonas, Erwinia, Bacteroides is proposed. A method for obtaining the nondissociating S-variants for stability of biologically active substances synthesized by cells has been suggested.     

Properties of cell wall peptidoglycan synthesized by amino acid deprived re1A mutants of Escherichia coli

Cell wall peptidoglycan synthesis in Escherichia coli is under stringent control. During amino acid deprivation, peptidoglycan synthesis is inhibited in re1A+ bacteria but not in re1A mutants. The relaxed synthesis of peptidoglycan by amino acid deprived re1A bacteria was inhibited by several beta-lactam antibiotics at concentrations which inhibited cell elongation in growing cultures suggesting that the transpeptidase activity of penicillin-binding protein (PBP-1B) was involved in this process. Structural studies on the peptidoglycan also indicated the involvement of transpeptidation in relaxed peptidoglycan synthesis. The peptidoglycan synthesized during amino acid deprivation was cross-linked to the existing cell wall peptidoglycan, and the degree of cross-linkage was the same as that of peptidoglycan synthesized by growing control cells. The relaxed synthesis of peptidoglycan was also inhibited by moenomycin, an inhibitor of the in vitro transglycosylase activities of PBPs, but the interpretation of this result depends on whether the transglycosylases are the sole targets of moenomycin in vivo. Most of the peptidoglycan lipoprotein synthesized by histidine-deprived re1A+ bacteria was in the free form as previously reported, possibly because of the restriction in peptidoglycan synthesis. In support of this proposal, most of the lipoprotein synthesized during histidine deprivation of re1A mutants was found to be covalently linked to peptidoglycan. Nevertheless, the peptidoglycan synthesized by amino acid deprived re1A bacteria was apparently deficient in bound lipoprotein as compared with peptidoglycan synthesized by normal growing control bacteria suggesting that the rate of lipoprotein synthesis during amino acid deprivation may be limiting.     

Rapid biosynthesis of PVP coated silver nanoparticles by <Emphasis Type="Italic">Kocuria rosea</Emphasis> and their antimicrobial activity

The need for more effective antimicrobial agent and propitious application of nanotechnology in therapeutics and diagnostics has prompted the research on ecofriendly synthesis of silver nanoparticles. The objective of present study was to investigate the antibacterial and antifungal activity of biologically synthesized silver nanoparticles. The silver nanoparticles were synthesized by extracellular method, using soil bacteria Kocuria rosea. The synthesized silver nanoparticles were characterized by UV-Visible spectroscopy, X-ray diffractometry (XRD), transmission electron microscopy (TEM) and fourier transformation infrared spectroscopy (FTIR). On the basis of TEM analysis, the synthesized nanoparticles were found to be spherical with an average size of 30–50 nm. The biologically synthesized silver nanoparticles showed significant antimicrobial activity against pathogens.     

Synthesis and antibacterial activity of 3-keto-6-O-carbamoyl-11,12-cyclic thiocarbamate erythromycin A derivatives

A series of 3-keto-6-O-carbamoyl-11,12-cyclic thiocarbamate erythromycin A derivatives has been synthesized. The best compounds in this series possess potent in vitro antibacterial activity against erythromycin-susceptible and erythromycin-resistant bacteria.     

Protein secretion in bacteria.

Most secretory proteins are synthesized as precursors with an amino-terminal signal peptide. Genetic identification of proteins essential for signal peptide dependent translocation to the Escherichia coli periplasm has led to the biochemical dissection of the secretion pathway. Additional mechanisms exist in Gram-negative bacteria for protein secretion to the extracellular environment.     

Inhibition of protein synthesis by aminoglycoside antibiotics in polyamine-requiring bacteria

The effect of streptomycin and other aminoglycosides on protein synthesis has been studied using various streptomycin-sensitive strains unable to synthesize polyamines. We have confirmed and extended our previous results showing that the strong inhibition of translation caused by the antibiotic in polyamine-supplemented bacteria was markedly reduced in polyamine-starved cells. The analysis of polypeptides synthesized in the absence and presence of streptomycin in bacteria grown with and without putrescine has shown that the antibiotic provoked the accumulation of low molecular weight peptides partially bound to ribosomes in polyamine-unstarved cells. On the contrary, the drug did not induce major alterations in the patterns of proteins obtained from polyamine-depleted bacteria. The addition of the antibiotic did not evoke any change of proteolytic activity.     

Synthesis of the α,ω-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway

Biotin synthesis requires the C7 α,ω-dicarboxylic acid, pimelic acid. Although pimelic acid was known to be primarily synthesized by a head to tail incorporation of acetate units, the synthetic mechanism was unknown. It has recently been demonstrated that in most bacteria the biotin pimelate moiety is synthesized by a modified fatty acid synthetic pathway in which the biotin synthetic intermediates are O-methyl esters disguised to resemble the canonical intermediates of the fatty acid synthetic pathway. Upon completion of the pimelate moiety, the methyl ester is cleaved. A very restricted set of bacteria have a different pathway in which the pimelate moiety is formed by cleavage of fatty acid synthetic intermediates by BioI, a member of the cytochrome P450 family.     

Crystal structure of a polyphosphate kinase and its implications for polyphosphate synthesis

Polyphosphate (polyP), a linear polymer of hundreds of orthophosphate residues, exists in all tested cells in nature, from pathogenic bacteria to mammals. In bacteria, polyP has a crucial role in stress responses and stationary-phase survival. Polyphosphate kinase (PPK) is the principal enzyme that catalyses the synthesis of polyP in bacteria. It has been shown that PPK is required for bacterial motility, biofilm formation and the production of virulence factors. PPK inhibitors may thus provide a unique therapeutic opportunity against antibiotic-resistant pathogens. Here, we report crystal structures of full-length Escherichia coli PPK and its complex with AMPPNP (beta-gamma-imidoadenosine 5-phosphate). PPK forms an interlocked dimer, with each 80 kDa monomer containing four structural domains. The PPK active site is located in a tunnel, which contains a unique ATP-binding pocket and may accommodate the translocation of synthesized polyP. The PPK structure has laid the foundation for understanding the initiation of polyP synthesis by PPK.     

Expression of protein IIIa of human adenovirus type 2 in Escherichia coli

We have constructed a plasmid encoding the protein IIIa gene of human adenovirus type 2. The gene was expressed under the control of the hybrid tac (trp-lac) promoter; the protein was synthesized at levels up to 5% of newly synthesized protein after IPTG induction. The protein IIIa produced in Escherichia coli has an apparent Mr on sodium dodecyl sulfate-polyacrylamide gels of 67 kDa, and was revealed with anti-adenovirus serum in Western blotting. The protein IIIa produced in bacteria was phosphorylated in the presence of [gamma-32P]ATP.     

Synthesis and antibacterial activity of 3-O-acyl-6-O-carbamoyl erythromycin A derivatives

A series of 3-O-acyl-6-O-carbamoyl erythromycin A derivatives has been synthesized. Several functional groups were identified as the optimal C3-substituents, and the best compounds in this series possess potent in vitro antibacterial activity against erythromycin-susceptible and erythromycin-resistant bacteria.     

Synthetic and pharmacological studies on some transition metal chelates involving N-pyrimidino benzamide-2-carboxylic acid as ligand

N-pyrimidino benzamide-2-carboxylic acid (NPBCA) and its Cu(II), Ni(II), Co(II), Zn(II), and Mn(II) chelates have been synthesized and characterized by using elemental analyses, molar conductance, molecular weight determination, magnetic moment, infrared, and electronic spectra. Antifungal activity of the synthesized compounds has been screened on common fungi, viz., Aspergillus niger, Aspergillus nidulense, and Candida albicans at 28 degrees C and antibacterial activity has been observed on gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria at 37 degrees C. Anti-inflammatory and ulcerogenic potential of the synthesized compounds have been discussed.     

Synthesis and antibacterial activity of 4'-O-heteroarylcarbamoyl derivatives of macrolide

A series of novel 4'-position modified macrolide derivatives has been synthesized via a facile procedure. Their in vitro antibacterial activities against constitutively erythromycin-resistant strains were evaluated. Among the derivatives tested, compound 8a which has 11,12-carbamate and 4'-O-heteroarylcarbamoyl groups was found to have potent activity against most resistant bacteria.     

Synthesis and evaluation of Ciprofloxacin derivatives as diagnostic tools for bacterial infection by Staphylococcus aureus

Development of target-specific diagnostic radiopharmaceuticals has always been a challenging task. For this purpose, design and development of the imaging-friendly variant of a potent antibiotic could aid in treatment planning and follow-up of patients with hard-to-diagnose bacterial infections. Fluoroquinolone analogues were synthesized taking the lead from Ciprofloxacin (the broad spectrum antibiotic) molecule. The idea of modifying fluoroquinolones, and subsequently labeling them, was to preserve their capacity to bind bacteria and thereby enable the compound to specifically target those microorganisms. Three compounds were thus synthesized as derivatives of Ciprofloxacin. The fluoroquinolone analogues were labeled with (99m)Tc by using (99m)Tc pertechnetate with high labeling efficiency for all the formulations. The complexes formed by chelation of (99m)Tc with our synthesized fluoroquinolone analogues showed good in vitro serum stability. The blood clearance study performed in New Zealand White rabbits exhibited a curve indicating the initial fast phase in which radiocomplexed drugs cleared from blood very quickly followed by a slow phase. The in vivo evaluation showed that fluoroquinolone-based radiopharmaceuticals bind to the bacteria present at the site of infection, which results in the retention of the agent at sites of active bacterial infection. The biodistribution data and the scintigrams demonstrated that Staphylococcus aureus bacteria in animal infection models took up the radiopharmaceutical formulations, confirming our hypothesis that (99m)Tc fluoroquinolone derivatives might be useful as diagnostic agents for targeted delivery in bacterial infections.     

Synthesis and evaluation of methyl ether derivatives of the vancomycin, teicoplanin, and ristocetin aglycon methyl esters

A series of methyl ether derivatives of the vancomycin, teicoplanin, and ristocetin aglycon methyl esters was synthesized and their antimicrobial activity was established. These derivatives exhibit increased activity against VanB resistant strains of bacteria equipotent with that observed with sensitive bacteria.     

Structural and microbial studies of some transition metal complexes

N-pyridinobenzamide-2-carboxylic acid has been synthesized. Its binary and ternary (using 8-hydroxy-quinoline as the other ligand) Cu(II), Ni(II), Co(II), and Zn(II) complexes have been synthesized and characterized by their elemental analysis, molecular weight determination, molar conductance, infrared and electronic spectral data, and magnetic measurements. Antibacterial activity of these ligands and their metal complexes has been determined on gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria at 37 degrees C, and antifungal activity has been determined on common fungi viz. Aspergillus niger, Aspergillus nidulense, and Candida albicans at 28 degrees C. A considerable increase in the biocidal activity of these ligands on being coordinated with metal ions has been reported.