Synthesis, Structural Characterization, Catalytic, Biological and α-Glucosidase Inhibitory Studies of Metal Complexes with Flavone Derivatives

Heterocyclic compounds, in particular oxygen-containing heterocyclic compounds, are of special interest to medicinal chemists because of their unusual biological properties. In the present study, the highly conjugated nitrogen heterocyclic scaffold comprised of flavone derivative with metal acetates to form metal chelates of the type [MIIL(OAc)2], flavone analogues (L); M=Co2+, Zn2+, Cu2+ and Ni2+. The above title compounds were characterized using composition analysis o fCHN and spectroscopic techniques. Based on spectroscopic and analytical measurements confirmed that square planar arrangements for the Co2+, Zn2+, Cu2+ and Ni2+ complexes. Antimicrobial efficacy of prepared complexes were assessed against A.flavus, A.niger, B.subtilis, E. coli, C. albicans and S.aureus. The anti-mycobacterial (H37Rv) efficacy of flavone analogues and its complexes were screened using MABA approach and compared with standard. The acetylcholinesterase (AChE) inhibitory effect of the ligand was examined to find out the therapeutic efficiency of compound in the treatment of neurodegenerative disorders. The synthesized ligand exhibited selective inhibition (AChE & BuChe) values (IC50:0.20(flavone analogue), 2.41 (Rivastigmine) and 3.01 µM (Galantamine), respectively. Further, the in vitro ant-inflammatory efficiency of metal chelates were performed with the help of egg albumin method. The α-glucosidase inhibition activity was also carried out for the prepared metal complexes.

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Novel Zinc(II) Complexes of Heterocyclic Ligands as Antimicrobial Agents: Synthesis, Characterisation, and Antimicrobial Studies

Bioinorganic Chemistry and Applications ◽

10.1155/2014/276598 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 15

Author(s):

Ramesh S. Yamgar ◽

Y. Nivid ◽

Satish Nalawade ◽

Mustapha Mandewale ◽

R. G. Atram ◽

...

Keyword(s):

Antimicrobial Activity ◽

Schiff Base ◽

Metal Complexes ◽

Antimicrobial Agents ◽

Spectroscopic Techniques ◽

Schiff Base Ligands ◽

E Coli ◽

Gram Positive Bacteria ◽

Antimicrobial Studies

The synthesis and antimicrobial activity of novel Zn(II) metal complexes derived from three novel heterocyclic Schiff base ligands 8-[(Z)-{[3-(N-methylamino)propyl]imino}methyl]-7-hydroxy-4-methyl-2H-chromen-2-one, 2-[(E)-{[4-(1H-1,2,4-triazol-1-ylmethyl)phenyl]imino}methyl]phenol, and (4S)-4-{4-[(E)-(2-hydroxybenzylidene)amino]benzyl}-1,3-oxazolidin-2-one have been described. These Schiff base ligands and metal complexes are characterised by spectroscopic techniques. According to these data, we propose an octahedral geometry to all the metal complexes. Antimicrobial activity of the Schiff base ligand and its metal complexes was studied against Gram negative bacteria:E. coliandPseudomonas fluorescens, Gram positive bacteria:Staphylococcus aureus,and also against fungi, that is,C. albicansandA. niger. Some of the metal complexes show significant antifungal activity (MIC < 0.2 μg/mL). The “in vitro” data has identified [Zn(NMAPIMHMC)2]·2H2O, [Zn(TMPIMP)2]·2H2O, and [Zn(HBABO)2]·2H2O as potential therapeutic antifungal agents againstC. albicansandA. niger.

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Flavone-Rich Fractions and Extracts from Oroxylum indicum and Their Antibacterial Activities against Clinically Isolated Zoonotic Bacteria and Free Radical Scavenging Effects

Molecules ◽

10.3390/molecules26061773 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1773

Author(s):

Patchima Sithisarn ◽

Piyanuch Rojsanga ◽

Pongtip Sithisarn

Keyword(s):

Antibacterial Activities ◽

Inhibitory Effect ◽

Total Flavonoid ◽

Total Phenolic ◽

Antibacterial Effects ◽

E Coli ◽

Young Fruit ◽

Oroxylum Indicum ◽

Zoonotic Bacteria

Oroxylum indicum extracts from the seeds collected from Lampang and Pattani provinces in Thailand, and young fruits and flowers exhibited in vitro display antioxidant and antibacterial activities against clinically isolated zoonotic bacteria including Staphylococcus intermedius, Streptococcus suis, Pseudomonas aeruginosa, β-hemolytic Escherichia coli and Staphylococcus aureus. The orange crystals and yellow precipitates were obtained from the preparation processes of the seed extracts. The orange-red crystals from the seeds collected from Lampang province exhibited strong in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging effects (EC50 value = 25.99 ± 3.30 μg/mL) and antibacterial effects on S. intermedius and β-hemolytic E. coli while the yellow precipitate from the same source exhibited only antioxidant activity. Quantitative analysis of phytochemicals in O. indicum samples by spectrophotometric and HPLC techniques showed that they contained different amounts of total phenolic, total flavonoid and three major flavones; baicalin, baicalein and chrysin contents. Young fruit extract, which contained low amounts of flavone contents, still promoted antibacterial effects against the tested bacteria with IC50 values lower than 1 mg/mL and MIC values between 4 to 10 mg/mL in S. intermedius, S. aureus and S suis while higher IC50 and MIC values against P. aeruginosa and β-hemolytic E. coli were found. From scanning electron microscopy, the extract of the young fruit of O. indicum promoted morphological changes in the bacterial cells by disrupting the bacterial cell walls, inducing leakage of the cellular content, and generating the abnormal accumulation of cells. The mechanism of action of the extract for this antibacterial effect may be the disruption of the cell membrane and abnormal cell aggregations. Regression analysis of the results suggests the correlation between total phenolic and total flavonoid contents and antioxidant and antibacterial effects. Baicalin was found to have a high correlation with an inhibitory effect against β-hemolytic E. coli while three unidentified peaks, which could be flavones, showed high correlations with an inhibitory effect against S. intermedius, S. suis, P. aeruginosa and S. aureus.

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The "in vitro" antifungal activity evaluation of propolis G12 ethanol extract on Cryptococcus neoformans

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46652007000200005 ◽

2007 ◽

Vol 49 (2) ◽

pp. 93-95 ◽

Cited By ~ 17

Author(s):

Fabrício Freitas Fernandes ◽

Amanda Latercia Tranches Dias ◽

Cíntia Lacerda Ramos ◽

Masaharu Ikegaki ◽

Antonio Martins de Siqueira ◽

...

Keyword(s):

Antifungal Activity ◽

Cryptococcus Neoformans ◽

Ethanol Extract ◽

Inhibitory Effect ◽

Biological Properties ◽

Standard Strain ◽

Antiviral Activities ◽

Prolonged Antibiotic Therapy ◽

In Vitro Antifungal Activity

Cryptococcosis is a worldwide disease caused by the etiological agent Cryptococcus neoformans. It affects mainly immunocompromised humans. It is relatively rare in animals only affecting those that have received prolonged antibiotic therapy. The propolis is a resin that can present several biological properties, including antibacterial, antifungal and antiviral activities. The standard strain C. neoformans ATTC 90112 was used to the antifungal evaluation. The tests were realized with propolis ethanol extract (PEE) G12 in concentrations from 0.1 to 1.6 mg mL-1. The evaluation of MIC and MFC were done according to DUARTE (2002)5. The inhibitory effect of PEE G12 on the fungal growing was seen at the concentration of 0.2 mg mL-1 and 1.6 mg mL-1 was considered a fungicidal one.

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Synthesis of Some Polysubstituted Nicotinonitriles and Derived Pyrido[2,3-d]pyrimidines asIn VitroCytotoxic and Antimicrobial Candidates

Journal of Chemistry ◽

10.1155/2016/2135893 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Hassan M. Faidallah ◽

Sherif A. F. Rostom ◽

Khalid A. Khan

Keyword(s):

Cell Line ◽

Colon Carcinoma ◽

Human Tumor ◽

Human Colon ◽

Pyrimidine Ring ◽

Inhibitory Effect ◽

Breast Adenocarcinoma ◽

Human Tumor Cell Lines ◽

E Coli

The synthesis of polysubstituted pyridines, in addition to some derived pyrido[2,3-d]pyrimidine ring systems supported with chemotherapeutically active functionalities, is described. They were evaluated for theirin vitrocytotoxic effects against three different human tumor cell lines (human colon carcinoma HT29, hepatocellular carcinoma Hep-G2, and Caucasian breast adenocarcinoma MCF7). Nine compounds displayed variable cytotoxic potential, among which alkylthio analogs33,34, and37emerged as the most active members, being almost twice as active as doxorubicin against the colon carcinoma HT29 cell line. In addition, the same three analogs showed a clear differential cytotoxic profile as they exhibited a marginal inhibitory effect on the growth of the normal nontransformed human foreskin fibroblast Hs27 cell line. Meanwhile, nineteen compounds were able to exhibit significant antibacterial activity against both Gram-positive and Gram-negative bacteria, together with moderate antifungal activities. The pyrido[2,3-d]pyrimidine-2(1H)-thione30together with its alkylthio derivatives33and34stemmed as the most active antimicrobial members being equipotent to ampicillin againstS. aureus,E. coli,andP. aeruginosa,together with a noticeable antifungal activity againstC. albicans.Compounds33and34could be considered as a promising template for possible dual antimicrobial-anticancer candidates.

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In-vitro Assessment of Biological Properties of Lipids Isolated from Gonads of Stomopneustes variolaris

Proceedings International ◽

10.33263/proceedings21.066066 ◽

2020 ◽

Vol 2 (1) ◽

pp. 66

Keyword(s):

Biological Effects ◽

Lipid Fraction ◽

Radical Scavenging ◽

Biological Properties ◽

Total Phenolic ◽

Klebsiella Pneumonia ◽

Spectroscopic Techniques ◽

Lipid Fractions ◽

Anti Fungal

Lipid fractions of gonads present in sea urchins serves as a source of bioactive agents with potent pharmaceutical properties. The present study reports the in-vitro biological effects of lipids isolated from gonads of sea urchin: Stomopneustes variolaris collected from the East coast of India. The extracted lipids were characterized by spectroscopic techniques such as GCMS and FTIR and tested for in-vitro biological effects. GCMS analysis of the lipid extract detected high levels of hexa triacontane (17.023 %), tetratetracontane (15.913%), and octacosane (15.628%) and low concentrations of oleic acid (2.206%) and sulfurous acid, pentadecy 2-propyl ester (1.744%). FTIR analysis identified rich composition of functional groups present in the lipids such as 3418.93 cm-1 (hydroxyl), 2921.08cm-1 and 2854.81 cm-1 (alkane), 2660.69 cm-1 (carboxylic acid), 1596.11 cm-1 (amine), 1291.76 cm-1 (aromatic amine). The lipid fraction evaluated by agar diffusion assay measured in terms of zone of inhibition showed bactericidal effects against gram-positive bacteria: Streptococcus aureus (30 mm); Pseudomonas aeruginosa (28.5 mm) and gram-negative bacteria: Escherichia coli (29.5 mm); Klebsiella pneumonia (27.5 mm) and Vibrio cholera (28 mm) respectively. The lipid fraction also showed an effective anti-fungal effect against C.albicans (25 mm). Further, the lipid fractions showed good radical scavenging effect against total phenolic, flavonoid content (15.12 mg GAE/g and 32.72 mg QE/g), and hydrogen peroxide radicals (IC50- 48.28mg/ml) confirming its anti-oxidant potential. Based on the observed results, it was identified that the lipid fraction of gonads of Stomopneustes variolaris demonstrated various biological effects such as bactericidal, anti-fungal and radical scavenging activities which could have a great scope in the formulation of biopharmaceutical agents.

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Biological Study of Transition Metal Complexes with Adenine Ligand

Proceedings ◽

10.3390/ecsoc-23-06601 ◽

2019 ◽

Vol 41 (1) ◽

pp. 77 ◽

Cited By ~ 1

Author(s):

Hamad M. I. Hasan ◽

Aaza I. Yahiya ◽

Safaa S. Hassan ◽

Mabrouk M. Salama

Keyword(s):

Metal Complexes ◽

Molar Conductance ◽

Molar Ratio ◽

Biological Study ◽

Ratio Method ◽

Spectroscopic Techniques ◽

Stoichiometric Ratio ◽

Metal Contents ◽

Molar Ratio Method

Adenine complexes were prepared with some of the first series transition metals in a stoichiometric ratio of 1: 2 (Mn+: L), where Mn+ = Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ ions. The Complexes were characterized by the physicochemical and spectroscopic techniques as electric conductivity, metal contents, IR, UV–Visible, and molar conductance techniques. The stoichiometric ratios of the synthesized complexes were confirmed by using molar ratio method. The dissociation constant of adenine ligand was determined spectrophotometrically. Solvent effect on the electronic spectra of the adenine ligand was examined using solvents with different polarities. The biological activity of adenine ligand and its metal complexes were tested in vitro against some selected species of fungi and bacteria. The results showed a satisfactory spectrum against the tested organisms.

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Full Capacity of Recombinant Escherichia coliHeat-Stable Enterotoxin Fusion Proteins for Extracellular Secretion, Antigenicity, Disulfide Bond Formation, and Activity

Infection and Immunity ◽

10.1128/iai.68.7.4064-4074.2000 ◽

2000 ◽

Vol 68 (7) ◽

pp. 4064-4074 ◽

Cited By ~ 16

Author(s):

Isabelle Batisson ◽

Maurice Der Vartanian ◽

Brigitte Gaillard-Martinie ◽

Michel Contrepois

Keyword(s):

Disulfide Bonds ◽

Secretory Pathway ◽

Biological Properties ◽

Leader Peptide ◽

Dependent Manner ◽

Reporter Protein ◽

E Coli ◽

Heat Stable

ABSTRACT We have successfully used the major subunit ClpG ofEscherichia coli CS31A fimbriae as an antigenic and immunogenic exposure-delivery vector for various heterologous peptides varying in nature and length. However, the ability of ClpG as a carrier to maintain in vitro and in vivo the native biological properties of passenger peptide has not yet been reported. To address this possibility, we genetically fused peptides containing all or part of the E. coli human heat-stable enterotoxin (STh) sequence to the amino or carboxyl ends of ClpG. Using antibodies to the ClpG and STh portions for detecting the hybrids; AMS (4-acetamido-4′-maleimidylstilbene-2,2′-disulfonate), a potent free thiol-trapping reagent, for determining the redox state of STh in the fusion; and the suckling mouse assay for enterotoxicity, we demonstrated that all ClpG-STh proteins were secreted in vitro and in vivo outside the E. coli cells in a heat-stable active oxidized (disulfide-bonded) form. Indeed, in contrast to many earlier studies, blocking the natural NH2 or COOH extremities of STh had, in all cases, no drastic effect on cell release and toxin activity. Only antigenicity of STh C-terminally extended with ClpG was strongly affected in a conformation-dependent manner. These results suggest that the STh activity was not altered by the chimeric structure, and therefore that, like the natural toxin, STh in the fusion had a spatial structure flexible enough to be compatible with secretion and enterotoxicity (folding and STh receptor recognition). Our study also indicates that disulfide bonds were essential for enterotoxicity but not for release, that spontaneous oxidation by molecular oxygen occurred in vitro in the medium, and that the E. coli cell-bound toxin activity in vivo resulted from an effective export processing of hybrids and not cell lysis. None of the ClpG-STh subunits formed hybrid CS31A-STh fimbriae at the cell surface ofE. coli, and a strong decrease in the toxin activity was observed in the absence of CS31A helper proteins. In fact, chimeras translocated across the outer membrane as a free folded monomer once they were guided into the periplasm by the ClpG leader peptide through the CS31A-dependent secretory pathway. In summary, ClpG appears highly attractive as a carrier reporter protein for basic and applied research through the engineering of E. coli for culture supernatant delivery of an active cysteine-containing protein, such as the heat-stable enterotoxin.

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Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat

Cells ◽

10.3390/cells8030251 ◽

2019 ◽

Vol 8 (3) ◽

pp. 251 ◽

Cited By ~ 2

Author(s):

Bernadette Lázár ◽

Gábor Brenner ◽

András Makkos ◽

Mihály Balogh ◽

Szilvia László ◽

...

Keyword(s):

Selective Inhibition ◽

Mucosal Damage ◽

Inhibitory Effect ◽

Intestinal Dysbiosis ◽

Bowel Diseases ◽

Direct Inhibitory Effect ◽

Cox 2 ◽

Small Intestinal

Intestinal dysbiosis is linked to numerous gastrointestinal disorders, including inflammatory bowel diseases. It is a question of debate if coxibs, selective inhibitors of cyclooxygenase (COX)-2, cause dysbiosis. Therefore, in the present study, we aimed to determine the effect of long-term (four weeks) selective inhibition of COX-2 on the small intestinal microbiota in the rat. In order to avoid mucosal damage due to topical effects and inflammation-driven microbial alterations, rofecoxib, a nonacidic compound, was used. The direct inhibitory effect of rofecoxib on the growth of bacteria was ruled out in vitro. The mucosa-sparing effect of rofecoxib was confirmed by macroscopic and histological analysis, as well as by measuring the intestinal levels of cytokines and tight junction proteins. Deep sequencing of bacterial 16S rRNA revealed that chronic rofecoxib treatment had no significant influence on the composition and diversity of jejunal microbiota. In conclusion, this is the first demonstration that long-term selective inhibition of COX-2 by rofecoxib does not cause small intestinal dysbiosis in rats. Moreover, inhibition of COX-2 activity is not likely to be responsible per se for microbial alterations caused by some coxibs, but other drug-specific properties may contribute to it.

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Lactobacillus inhibitor production against Escherichia coli and coaggregation ability with uropathogens

Canadian Journal of Microbiology ◽

10.1139/m88-063 ◽

1988 ◽

Vol 34 (3) ◽

pp. 344-351 ◽

Cited By ~ 159

Author(s):

Gregor Reid ◽

Jacqueline A. McGroarty ◽

Rosanne Angotti ◽

Roger L. Cook

Keyword(s):

Escherichia Coli ◽

Defense Mechanism ◽

Inhibitory Effect ◽

Second Phase ◽

Vitro Assay ◽

E Coli ◽

Host Defense Mechanism ◽

Important Host ◽

Two Phases

Previous investigations have shown that certain strains of lactobacilli can competitively exclude uropathogens from attaching to uroepithelial cells and from causing urinary tract infection in animals. The finding of an inhibitory effect produced by Lactobacillus casei ssp. rhamnosus GR-1 against the growth of uropathogens was investigated further using two Escherichia coli indicator strains Hu 734 and ATCC 25922. There were two phases to the inhibitor studies. The first one using an agar sandwich technique showed that the inhibitor activity was heat stable and inhibitory to the E. coli. The second phase showed that MRS broth provided optimum lactobacilli growth and inhibitor production. In addition, the inhibition was present under conditions buffering for acid and pH. The data indicated that the inhibitory effect was not due to bacteriophages or hydrogen peroxide. Strain GR-1 was found to coaggregate with E. coli ATCC 25922 in urine, a phenomenon that has not previously been reported for urogenital bacteria. An in vitro assay system was developed to study the coaggregation of various lactobacilli and uropathogens. The results demonstrated that highest coaggregation scores occurred after 4 h incubation at 37 °C with lactobacilli and two type-1 fimbriated E. coli strains. Of the nine lactobacilli strains tested, each was found to coaggregate with 2 or more of the 13 uropathogens. The dominance of inhibitor-producing lactobacilli on the urogenital epithelium and the ability of these organisms to interact closely with uropathogens would constitute an important host defense mechanism against infection.

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Evaluation of mesoporous silica nanoparticles-based nanoantibiotics and capsaicin on E. coli and S. aureus biofilms

10.5194/biofilms9-133 ◽

2020 ◽

Author(s):

Anna Slita ◽

Prakirth Govardhanam ◽

Ida Opstad ◽

Didem Sen Karaman ◽

Jessica Rosenholm

Keyword(s):

Mesoporous Silica ◽

Silica Nanoparticles ◽

High Throughput ◽

Mesoporous Silica Nanoparticles ◽

Inhibitory Effect ◽

E Coli ◽

Resazurin Assay ◽

Antibiotic Drug ◽

High Throughput Assay

Introduction Since antibiotics were discovered, bacteria have demonstrated the ability to develop resistance by many different mechanisms. According to WHO reports from 2014, there has been an alarming increase in the antibiotic resistant bacterial strains in most parts of the world1. Our previous results showed that a nanoantibiotic (NAB) design created in our laboratory2, composed of a cerium oxide core, mesoporous silica shell loaded with capsaicin, and a chitosan coating, are effective against planktonic E. coli. However, most of the pathogenic bacteria form biofilms during infections. That is why the next stage of studying NAB is to determine whether they are effective against biofilms of different species. Moreover, the results of NAB efficiency against planktonic E. coli did not clearly show the contribution of the antibiotic drug component of NAB &#8211; capsaicin. Hence, the first step of the current study is to determine whether and to what degree, mesoporous silica nanoparticles (MSN) &#8211; serving as NAB model in this case - penetrate biofilms as a function of particle shape and surface coating; as well as finding the efficient concentration of capsaicin against E. coli and S. aureus &#160;to optimize the NAB dosing against biofilms. &#160; Aim To check in vitro penetration of MSN on S. aureus biofilm and antibacterial activity of NAB and pure capsaicin on E. coli and S. aureus biofilms. Methods To investigate NAB efficiency on biofilms MBEC-high-throughput assay3 was performed. Equal biofilms formed on peg-lids were incubated with different concentrations of NAB and capsaicin. After different time point biofilms were sonicated and plated on agar plated to perform CFU counting. To determine the efficient concentration of capsaicin, biofilms were formed in 12 well plates and then incubated with different concentrations of capsaicin. To visualize inhibitory effect, plating for CFU counting and Resazurin assay were applied. To evaluate the penetration of particles, labeled and non-labeled particles were added to fully grown St. aureus biofilms, incubated and visualized with confocal microscopy and structured illumination microscopy. &#160; Results <ol> <li>Through two different microscopy techniques penetration of particles into biofilm and their localization next to bacteria cells were observed.</li> <li>In MBEC-high-throughput assay no inhibitory effect of NAB against E. coli biofilms was detected in comparison with untreated bacteria.</li> <li>Resazurin assay and CFU counting method allowed us to determine the most efficient concentration of capsaicin against E. coli and St. aureus biofilms.</li> </ol> &#160; Conclusion <ol> <li>Use of MSN and NAB in particular to deliver active antibacterial agents inside the biofilm is justified.</li> <li>We cannot claim that NAB does not demonstrate any activity against E. coli biofilms, though we can suggest that the peg-lid set up is not sufficient for the NAB design. Further experiments are required.</li> <li>The next step is to test different concentrations of NAB against biofilms with more appropriate methods than MBEC-high-throughput assay. These results will allow us to make conclusions about the benefits of NAB in comparison with pure capsaicin.</li> </ol> &#160; References <ol> <li>Govardhanam, N.P. (2017). Development of nanoantibiotics and evaluation via in vitro and in vivo imaging. University of Turku, Finland.</li> <li>Ventola, C. Lee.&#160;Pharmacy and Therapeutics&#160;40.4: 277, 2015</li> <li>Harrison, J. et al., BMC microbiology 5(1), 53, 2005.</li> </ol>

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