High Antibiotic Activity Research Articles

Structural Characterization and Bacteriostatic and Cytotoxicity to 3T3 Cells Study of Oligobiguanidine (Polyhexamethylene Biguanidine Hydrochloride) and its 3-Glycidoxypropyltrimethoxysilane Derivatives

In this paper, polyhexamethylene biguanidine hydrochloride (PHMB) oligomers were prepared by polycondensation of hexamethylenediamine, hydrochloric acid and 1,6-hexamethylenebis(dicyanamide); the organosilicon derivatives of PHMB oligomers (PHMB-Si) were prepared in solution through the reaction of PHMB and 3-Glycidoxypropyltrimethoxysilane (GLYMO). The analyses of FT-IR, 1H and 13C-NMR, elemental analysis, and TGA showed that the PHMB-Si was synthesized successfully. The relationship between antibiotic activity and viscosity-average molecular weight of PHMB; the relationship between antibiotic activity and the content of organosilicon in PHMB-Si were investigated. The experimental results revealed that the antibacterial activity of PHMB yielded the maximum at the viscosity-average molecular weight of 9000. The higher ratio of GLMYO in PHMB-Si, the higher antibiotic activity of PHMB-Si was. The minimal bactericidal concentration (MBC) of PHMB was 10 ppm, and the MBC of PHMB-Si was 5 ppm. The results showed there was an obvious synergy of PHMB-Si in bacteriostatic activity than PHMB.

Activity of extracellular compounds of Pseudomonas sp. against Xanthomonas axonopodis in vitro and bacterial leaf blight in eucalyptus

Bacterial leaf blight caused by Xanthomonas axonopodis is a major problem in the production of eucalyptus seedlings. The pathogen causes leaf lesions that reduce the photosynthetic area and limit plant growth. The objective of this study was to evaluate the antibiotic activity of secondary metabolic compounds of a Pseudomonas sp. against X. axonopodis, following extraction with dichloromethane and fractionation by vacuum liquid chromatography. The antibiotic activity of an ethyl acetate phase (F3 fraction) was determined by agar diffusion tests and bioautography. The minimum inhibitory concentration of F3 fraction and the action of F3 on the cell morphology of X. axonopodis was determined by scanning electron microscopy. Electron microscopy revealed changes in exopolysaccharides and morphology of treated cells. When eucalyptus seedlings were sprayed with the F3 fraction before or after inoculation with X. axonopodis in a greenhouse experiment the number of leaf lesions was respectively 93.9% and 89.7% lower than in untreated control plants. High antibiotic activity of the F3 fraction against X. axonopodis and leaf blight suggests that it has potential to control the disease in eucalyptus seedlings.

Comparative bioactivity of dhaman grass root extracts in different polar solvents against plant and human pathogens

Background: Cenchrus ciliaris L. (Poaceae) is a very suitable and highly nutritive grass for environmental conditions of the desert; yet, no antimicrobial work has been done on this grass. Aim: To estimate in vitro the antibiotic activity of root extracts of C. ciliaris in various polar solvents to use the grass as a possible source for new antimicrobial compounds against important plant and human pathogens. Settings and Design: The antibiotic activity of C. ciliaris root extracts were evaluated against a few medically important pathogens including Gram-negative bacteria Proteus mirabilis, Klebsiella pneumoniae, Agrobacterium tumefaciens, and the fungi, Aspergillus niger. Materials and Methods: Dried, powdered, and weighted root material was successively extracted with different polar solvents [hexane, petroleum ether, toluene, benzene, isopropyl alcohol, chloroform, ethyl acetate, acetone, ethanol, glacial acetic acid (GAA), and water] using a Soxhlet assembly. Antibiotic activity was performed by using disc diffusion assay followed by determination of minimum inhibitory concentrations by broth dilution method, against sensitive bacteria (with good inhibition zone). Most of the extracts, at higher concentrations, showed varying degrees of inhibitory activity against selected bacteria. Statistical Analysis: Mean value and standard deviation were calculated for the test bacteria and fungi. Data were analysed by one-way analysis of variance (ANOVA) and P values were considered significant at P<0.05. Results and Conclusions: Results revealed that the highest antibiotic activity was exhibited by the water and GAA extracts against P. mirabilis, followed by isopropyl alcohol extract against K. pneumoniae and A. tumefaciens. Water extract was observed to be the most active extract with maximum zone of inhibition against A. tumefaciens (plant pathogen) as compared to all other extracts. Key words: Antibiotic activity, Cenchrus grass, minimum inhibitory concentration, one of inhibition

ChemInform Abstract: One‐Pot Enantioselective Synthesis of Functionalized Pyranocoumarins and 2‐Amino‐4H‐chromenes: Discovery of a Type of Potent Antibacterial Agent.

AbstractThe chromene derivative (XVII) shows high antibiotic activity against Staphylococcus aureus.

Polycationic Gramicidin S Analogues with Both High Antibiotic Activity and Very Low Hemolytic Activity

The substitution of each constituent amino acid residue of gramicidin S (GS), cyclo(-Val(1,1')-Orn(2,2')-Leu(3,3')-D-Phe(4,4')-Pro(5,5')-)(2) with Lys residue indicated that each side chain structure of the constituent amino acid residues affect largely the antibiotic activity and hemolytic activity of GS. Further, the substitution of D-Phe(4,4') and Pro(5,5') residues with basic amino acid residues as a Lys residue results the high antibiotic activity and the very low hemolytic activity. Thus, we have found novel positions on the scaffold of GS at D-Phe(4,4') and Pro(5,5') residues whose modification will significantly increase the therapeutic index.

Fatty acyl-gramicidin S derivatives with both high antibiotic activity and low hemolytic activity

In the present study, novel eight GS derivatives having the octanoyl-(Lys)(n)- moieties, cyclo{-Val-Orn-Leu-d-Phe-Pro(4β-NH-X)-Val-Orn-Leu-d-Phe-Pro-} {X=-H (1), and -(Lys)(n)-CO(CH(2))(6)CH(3)n=0 (2), 1 (3), 2 (4), and 3 (5)} and cyclo{-Val-Orn-Leu-d-Phe-Pro(4α-NH-X)-Val-Orn-Leu-d-Phe-Pro-} {X=-H (6), and -(Lys)(n)-CO(CH(2))(6)CH(3)n=1 (7), and 2 (8)} were synthesized. Among them, 4, 5 and 8 result the high antibiotic activity against both Gram-positive and Gram-negative microorganisms tested. In addition, 4 and 5 showed very low hemolytic activity compared with that of GS. Thus, the introduction of the excess amino groups and the fatty acyl moiety to the γ-NH(2) group of Pro(5) residue in GS molecule lowered the unwanted hemolytic activity and enhanced the desired antibiotic activity.

Lytic activity of the virion-associated peptidoglycan hydrolase HydH5 of Staphylococcus aureusbacteriophage vB_SauS-phiIPLA88

BackgroundStaphylococcus aureus is a food-borne pathogen and the most common cause of infections in hospitalized patients. The increase in the resistance of this pathogen to antibacterials has made necessary the development of new anti-staphylococcal agents. In this context, bacteriophage lytic enzymes such as endolysins and structural peptidoglycan (PG) hydrolases have received considerable attention as possible antimicrobials against gram-positive bacteria.ResultsS. aureus bacteriophage vB_SauS-phiIPLA88 (phiIPLA88) contains a virion-associated muralytic enzyme (HydH5) encoded by orf58, which is located in the morphogenetic module. Comparative bioinformatic analysis revealed that HydH5 significantly resembled other peptidoglycan hydrolases encoded by staphylococcal phages. The protein consists of 634 amino acid residues. Two putative lytic domains were identified: an N-terminal CHAP (cysteine, histidine-dependent amidohydrolase/peptidase) domain (135 amino acid residues), and a C-terminal LYZ2 (lysozyme subfamily 2) domain (147 amino acid residues). These domains were also found when a predicted three-dimensional structure of HydH5 was made which provided the basis for deletion analysis. The complete HydH5 protein and truncated proteins containing only each catalytic domain were overproduced in E. coli and purified from inclusion bodies by subsequent refolding. Truncated and full-length HydH5 proteins were all able to bind and lyse S. aureus Sa9 cells as shown by binding assays, zymogram analyses and CFU reduction analysis. HydH5 demonstrated high antibiotic activity against early exponential cells, at 45°C and in the absence of divalent cations (Ca2+, Mg2+, Mn2+). Thermostability assays showed that HydH5 retained 72% of its activity after 5 min at 100°C.ConclusionsThe virion-associated PG hydrolase HydH5 has lytic activity against S. aureus, which makes it attractive as antimicrobial for food biopreservation and anti-staphylococcal therapy.

Novel Cycloundecapeptides Related to Gramicidin S with Both High Antibiotic Activity and Low Hemolytic Activity

To find candidates with high antimicrobial and low hemolytic activities, many gramicidin S (GS) analogs of various ring sizes have been designed and synthesized. However, syntheses of antimicrobially active analogues of GS having a disordered symmetry structure from C(2) have almost never been reported, because the stable, amphiphilic β-sheet structure of GS with C(2) symmetry is considered essential for its strong antibacterial activity. In the present studies, novel thirteen cycloundecapeptides 1-13 related to GS were synthesized and examined. Among them, cyclo(-Va1(1)-Orn(2)-Leu(3)-D-Phe(4)-X(5)-Pro(6)-Val(7)-Orn(8)-Leu(9)-D-Phe(10)-Pro(11)-) (X=Lys (10), Orn (11), Arg (12) and Lys(Lys) (13)) resulted in high antibiotic activity against both Gram-positive and Gram-negative microorganisms tested. In addition, 11 showed low toxicity against sheep blood cells compared with that of GS. Further, circular dichroism (CD) spectra of 10-13 had a curve similar to each other, suggesting that the conformations of these analogues in methanol are similar to each other. However, CD spectra of 10-13 were different from that of GS in the 190-210 nm region. These results suggest that the presences of one added amino acid residue at position 5 of 10-13 might be partially effective through a structural change in the biological activity of 10-13. In addition, the structural modifications at position 5 lower the undesirable hemolytic activity and enhance the desirable antibiotic activity.

Novel gratisin derivatives with high antimicrobial activity and low hemolytic activity

The substitution of each constituent amino acid residue of gratisin (GR) with Ala residue indicated that each side chain structure of the constituent amino acid residues affect largely the antibiotic and hemolytic activities of GR. Among them, the substitution of Pro residues at positions 5 and 5′ with a cationic amino acid residues (Lys and Arg) results the high antibiotic activity and the low toxicity against human blood cells. Thus, we have found a novel position on the scaffold of GR at Pro5,5′ residues whose modification will significantly lower the unwanted hemolytic activity and enhance the desired antibiotic activity.

New Antifungal Bacteriocin-Synthesizing Strains of &lt;i&gt;Lactococcus lactis&lt;/i&gt; ssp. &lt;i&gt;lactis&lt;/i&gt; as the Perspective Biopreservatives for Protection of Raw Smoked Sausages

Problem statement: Screening for the effective bacteriocin-synthesizing strains of Lactococcus lactis as the perspective biopreservatives was performed. We used a raw milk and dairy products from different climatic regions as well as from powerful drinks of mixed lactic acid and alcoholic fermentation: kurunga, kumiss and Iranian “Dough”, that were widely used by local population to prevent diseases. Approach: The special interest was paid to isolates of lactococci with antagonistic activity. According to their morphological, cultural, physiological, biochemical properties and sequence of 16S rRNA gene they were identified as Lactococcus lactis ssp. lactis. Only nine from the selected 94 strains expressed a broad spectrum of activity against Gram-positive and Gramnegative bacteria including pathogens (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Salmonella gallinarum), moulds (Aspergillus, Fusarium, Penicillium genera), as well as yeasts (Rhodotorula, Candida). Results: It reveals the unique biological properties for isolated natural strains of Lactococcus lactis species. Most effective new bacteriocin-synthesizing strains 194 and K-205 were isolated from raw cow milk and kurunga from Buryatia. These strains had high antibiotic activity up to 3600 and 2700 IU mL-1 as compared to nisin and up to 2500-1700 IU mL-1 as compared to fungicidal antibiotic nistatin. In our experiments we used raw smoked sausages that were infected with fungi. The identification of this infection showed the presence of Eurotium repens de Bary on the sausages. Treatment of the raw smoked sausages with cultural broth of L.lactis ssp. lactis 194 and K-205 inhibited growth of these microorganisms. After treatment the sausages had longer shelf-life and was in accordance with basal production data (Russian State Standard Specification 16131-86). Conclusion: The results of this study indicated that the treatment with lactococci strains can prevent a contamination of raw smoked sausages by potential food-borne pathogens.

A DFT investigation of structure and spectroscopic properties of pyrazolo[4,3- e][1,2,4]triazine natural products

The controversial structural issue of a set of pyrazolo[4,3- e][1,2,4]triazine natural products with high antibiotic activity has been tackled with density functional theory calculations. The electronic structure of these nitrogen-rich drugs has been characterized by analyzing the 13C NMR chemical shifts and UV-visible absorption spectra that are most sensitive to stereoelectronic factors. In particular, the remarkably changeable pattern of the π → π ∗ excitations accounts for the palette of bright colours exhibited by these compounds.

Stereochemical Determination and Complex Biosynthetic Assembly of Etnangien, a Highly Potent RNA Polymerase Inhibitor from the Myxobacterium Sorangium cellulosum

A potent novel analogue of the natural macrolide antibiotic etnangien, a structurally unique RNA polymerase inhibitor from myxobacteria, is reported. It may be readily obtained from fermentation broths of Sorangium cellulosum and shows high antibiotic activity, comparable to that of etnangien. However, it is much more readily available than the notoriously labile authentic natural product itself. Importantly, it is stable under neutral conditions, allowing for elaborate NMR measurements for assignment of the 12 hydroxyl- and methyl-bearing stereogenic centers. The full absolute and relative stereochemistries of these complex polyketides were determined by a combination of extensive high-field NMR studies, including J-based configuration analysis, molecular modeling, and synthetic derivatization in combination with an innovative method based on biosynthetic studies of this polyketide which is also presented here. A first look into the solution conformation and 3D structure of these promising macrolide antibiotics is reported. Finally, the complete biosynthetic gene cluster was analyzed in detail, revealing a highly unusual and complex trans-AT type polyketide biosynthesis, which does not follow colinearity rules, most likely performs programmed iteration as well as module skipping, and exhibits HMG-CoA box-directed methylation.

Optimization of fermentation condition for antibiotic production by Xenorhabdus nematophila with response surface methodology

To evaluate the influence of environmental parameters on the production of antibiotics (xenocoumacins and nematophin) by Xenorhabdus nematophila and enhance the antibiotic activity. Response surface methodology (RSM) was employed to study the effects of five parameters (the initial pH, medium volume in flask, rotary speed, temperature and inoculation volume) on the production of antibiotics in flask cultures by X. nematophila YL001. A 2(5-1)-factorial central composite design was chosen to explain the combined effects of the five parameters and to design a minimum number of experiments. The experimental results and software-predicted values of production of antibiotics were comparable. The statistical analysis of the results showed that, in the range studied, medium volume in flask, rotary speed, temperature and inoculation volume had a significant effect (P < 0.05) on the production of antibiotics at their individual level, medium volume in flask and rotary speed showed a significant influence at interactive level and were most significant at individual level. The maximum antibiotic activity was achieved at the initial pH 7.64, medium volume in 250 ml flask 25 ml, rotary speed of 220 rev min(-1), temperature 27.8 degrees C and inoculation volume of 15.0%. Maximum antibiotic activity of 331.7 U ml(-1) was achieved under the optimized condition. As far as known, there are no reports of production of antibiotic from X. nematophila by engineering the condition of fermentation using RSM. The results strongly support the use of RSM for fermentation condition optimization. The optimization of the environmental parameters resulted not only in a 43.4% higher antibiotic activity than unoptimized conditions but also in a reduced amount of the experiments. The chosen method of optimization of fermentation condition was efficient, relatively simple and time and material saving. This study should contribute towards improving the antibiotics activity of X. nematophila. Integrated into a broader study of the impact of environmental factors on the production of antibiotic, this work should help to build more rational control strategy, possibly involving scale-up of production of antibiotics by X. nematophila.

Julichrome Q6 Glucuronide, a Monomeric Subunit of the Julimycin B-I Complex from a Terrestrial Streptomyces sp.

The terrestrial Streptomyces sp. isolate GW6225 afforded julichrome Q 6 glucuronide ( 9), the first monomeric member of the julimycin-B complex, and additionally the julichromes Q 1.2 ( 7a), Q 1.5 ( 7b), and Q 3.5 ( 8), which were fully characterized by 2D NMR spectra. Additional new microbial compounds were 4-acetylchrysophanol ( 6a) and N-phenyl-beta-naphthylamine ( 10). The isomeric N-phenyl-alpha-naphthylamine ( 11) was found in the marine Streptomyces sp. B8335 and was also characterized. The high antibiotic activity of Streptomyces sp. GW6225 extracts was probably due to the thiazolyl cyclopeptide nosiheptide.

Enhanced antibiotic activity of Xenorhabdus nematophila by medium optimization

Nutrition had highly influence on the antibiotic production by Xenorhabdus nematophila YL001. Glucose and peptone were identified as the best carbon and nitrogen sources that significantly affected antibiotic production using one-factor-at-a-time approach. Response surface methodology was applied to optimize the medium constituents (Glucose, peptone and minerals) for antibiotic production by X. nematophila YL001. Higher antibiotic activity (328.9 U/ml) was obtained after optimizing medium components. The optimal levels of medium components were (g/l): glucose 6.13, peptone 21.29, MgSO 4 · 7H 2O 1.50, (NH 4) 2SO 4 2.46, KH 2PO 4 0.86, K 2HPO 4 1.11 and Na 2SO 4 1.72. An overall 16% and 35% increase in antibiotic activity were obtained as compared with mean observed response (283.7 U/ml) at zero level of all variables and YSG medium.

Influence of C-terminal amidation on the antimicrobial and hemolytic activities of cationic α-helical peptides

Abstract The effect of C-terminal amidation on the antimicrobial and hemolytic activities of antimicrobial peptides was studied using three cationic peptides which form amphiphilic α-helices when bound to membranes. The natural antimicrobial peptide PGLa, the designer-made antibiotic MSI-103, and the cell-penetrating "model amphipathic peptide" (MAP) are all amidated in their original forms, and their biological activities were compared with the same sequences carrying a free C-terminus. It was found that, in general, a free COOH-terminus reduces both the antimicrobial activity and the hemolytic side effects of the peptides. The only exception was observed for MSI-103, whose antimicrobial activity was not decreased in the acid form. Having shown that the therapeutic index (TI) of this novel peptide is significantly higher than for the other tested peptides, with high antibiotic activity and little undesired effects, we suggest that it could be a useful starting point for further development of new peptide antibiotics.

Antimicrobial Leucocin Analogues with a Disulfide Bridge Replaced by a Carbocycle or by Noncovalent Interactions of Allyl Glycine Residues

The type IIa bacteriocins are antimicrobial peptides isolated from lactic acid bacteria that act as food preservation agents and have nanomolar activity against pathogens such as Listeria monocytogenes. Previous reports with mutant bacteriocins indicate that the conserved disulfide bridge between cysteine residues 9 and 14 in bacteriocins such as leucocin A (1) is critical for antibiotic properties, which are mediated by target membrane receptor proteins belonging to the mannose phosphotransferase (mpt) system. To examine whether the disulfide can be replaced by an olefin moiety, [9,14]-dicarba leucocin A (4) was made by on-resin ring closing metathesis of allyl glycine residues using a new protocol suitable for larger hydrophobic peptides. Carbocyclic analogue 4 still displays nanomolar activity but is about 10-fold less potent than 1. Surprisingly, the acyclic [9,14]-diallyl leucocin A (5) displays even higher antibiotic activity than 4 and is as effective as the parent, leucocin A (1). We attribute this activity to hydrophobic intermolecular interactions of the diallyl side chains of the acyclic bacteriocin 5 that assist realization of the correct conformation at the receptor active site. Such substitutions in other systems may allow linear acyclic peptides to mimic the biological activity of natural disulfide ring-containing parents.

Preparation and Antibiotic Activity of Monobactam Analogues of Nocardicins

ABSTRACT A series of diverse β-lactam analogues of nocardicins with interesting antimicrobial properties were prepared. Coupling of glucosamine to these compounds improved their water solubility. Aminoacid derivatives produced a stereoinduction on the quaternary enantiotopic carbon of the starting compound 1. Evaluation of their antimicrobial activity showed that the introduction of α-aminoacids to monobactams increased their activity. The importance of asymmetric carbon is exemplified by the higher antibiotic activity of L-α-aminoacids than the D-series. No significant difference was observed between fluorinated and non-fluorinated monobactams.

The Role of Bacteria of Digestive Tract of Quails in the Formation of Their Immunological Status

Investigations on the composition and antibiotic activities of bacteria of digestive tract of 4-month-old japan quails (Coturnix coturnix japonica) which were not vaccinated or vaccinated twice with Salmonella enteritidis Talovac 109 SE vaccine demonstrated that in digestive tracts of both vaccinated and unvaccinated quails the Enterobacteriaceae family bacteria remarkably dominated. The bacteria of digestive tract of quails are characterized by very high antibiotic activity (78, 26 % of unvaccinated quails bacteria and 91,66% of vaccinated ones exhibited antagonistic activities). Vaccination appears to increase the number of antibiotically active bacteria, extend the spectrum of their effect, and enlarge inhibition zone.

In vitro expression of beta-lactam-induced response by clinical gram-negative bacteria with the potential for inducible beta-lactamase production.

The aim of this study was to investigate the in vitro beta-lactam-induced response of clinical Gram-negative bacteria with the potential for inducible beta-lactamase production, in order to be able to discriminate diagnostically between inducible and constitutive beta-lactamase production. A total of 242 clinical Gram-negative isolates of species with inducible chromosomal beta-lactamase were subjected to a disc diffusion test involving agar dilution of the inducers. Cefoxitin (FOX) and imipenem (IPM) were used as inducers and the antibiotics ceftazidime, cefuroxim, cefazolin, amoxycillin and piperacillin as indicators. beta-lactamase induction was observed at concentrations as low as 0.06 mg/l FOX or 0.008 mg/l IPM. In our test, 2 types of antibiotic phenomenon often interfered with inductive effects. Firstly a minor antibiotic effect was seen as an increase in inhibition zones at increasing inducer concentration and, secondly, absence of growth was caused by too high antibiotic activity of the inducer. The induced decrease in zone diameters varied strongly (up to 22 mm). Expressions of resistance were combined in inducibility profiles. Compilation of these profiles allowed an explanation to be proposed for the multi(-beta-lactam)-resistance, i.e. that most isolates combine inducible beta-lactamase synthesis with one or more resistance-potentiating factors. Only a few isolates demonstrated non-inducible resistance, which was probably due to mutation-mediated de-repression of beta-lactamase synthesis. The test presented here may be well-suited to studying inducibility of beta-lactamase production in the diagnostic laboratory.