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Hafizah Chenia
University of KwaZulu-Natal, Microbiology, Faculty Member
The biosynthesis of silver nanoparticles (AgNPs) from Diospyros villosa leaves and stem bark extracts is described. The stem bark AgNPs of D. villosa synthesized at 80 °C (S80) showed good scavenging activity with a lower IC50 value of... more
The biosynthesis of silver nanoparticles (AgNPs) from Diospyros villosa leaves and stem bark extracts is described. The stem bark AgNPs of D. villosa synthesized at 80 °C (S80) showed good scavenging activity with a lower IC50 value of 8.75 µg·mL−1 compared to ascorbic acid (9.58 µg·mL−1). The total phenol content of the S80 AgNPs was measured and found to be 10.22 ± 0.14 mg.g−1 gallic acid equivalence (GAE). Bacterial growth inhibition (% GI) and violacein inhibition (% VI) of 10.08% and 58.83%, respectively, was observed against C.subtsugae CV017 with leaf AgNPs synthesized at 80 °C (L80) at 80 μg·mL−1. Stem bark AgNPs synthesized at room temperature (SRT) also indicated % GI of 13.83% and % VI of 65.97% against C. subtsugae CV017 at 160 μg·mL−1. Leaf AgNPs of D. villosa synthesized at room temperature (LRT), showed % GI of 29.07% and % VI of 56.53%, respectively, against C. violaceum ATCC 12472 at 320 μg·mL−1. The L80 and SRT at 160 μg·mL−1 and LRT at 320 μg·mL−1 may be considere...
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IntroductionThere is a growing demand for effective technologies for the delivery of antigen to antigen-presenting cells (APCs) and their immune-activation for the success of DNA vaccines. Therefore, dendritic cell (DC)-targeting T7... more
IntroductionThere is a growing demand for effective technologies for the delivery of antigen to antigen-presenting cells (APCs) and their immune-activation for the success of DNA vaccines. Therefore, dendritic cell (DC)-targeting T7 phages were used as a vehicle to deliver DNA vaccine.MethodsIn this study, a eukaryotic expression plasmid pEGFP-C1-HA2-AS containing the HA2 gene derived from the avian H5N1 virus and an anchor sequence (AS) gene required for the T7 phage packaging process was developed. To verify the feasibility of phage delivery, the plasmid encapsulated in DC-targeting phage capsid through the recognition of AS was evaluated both in vitro and in vivo. The pEGFP-C1-HA2-AS plasmid could evade digestion by DNase I by becoming encapsulated into the phage particles and efficiently expressed the HA2 antigen in DCs with the benefit of DC-targeting phages.ResultsFor chickens immunized with the DC-targeting phage 74 delivered DNA vaccine, the levels of IgY and IgA antibodies,...
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Dendritic cells (DCs) are the antigen-presenting cells that initiate and direct adaptive immune responses, and thus are critically important in vaccine design. Although DC-targeting vaccines have attracted attention, relevant studies on... more
Dendritic cells (DCs) are the antigen-presenting cells that initiate and direct adaptive immune responses, and thus are critically important in vaccine design. Although DC-targeting vaccines have attracted attention, relevant studies on chicken are rare. A high diversity T7 phage display nanobody library was constructed for bio-panning of intact chicken bone marrow DCs to find DC-specific binding nanobodies. After three rounds of screening, 46 unique sequence phage clones were identified from 125 randomly selected phage clones. Several DC-binding phage clones were selected using the specificity assay. Phage-54, -74, -16 and -121 bound not only with chicken DCs, but also with duck and goose DCs. In vitro, confocal microscopy observation demonstrated that phage-54 and phage-74 efficiently adsorbed onto DCs within 15 min compared to T7-wt. The pull-down assay, however, did not detect any of the previously reported proteins for chicken DCs that could have interacted with the nanobodies ...
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Additional file 1: Table S1. Primer sequences for PCR amplification of ESBL and pAmpC genes. Table S2. Antimicrobial susceptibility for ESBL-positive E. coli blood isolates (n = 17). Table S3. Antimicrobial susceptibility for... more
Additional file 1: Table S1. Primer sequences for PCR amplification of ESBL and pAmpC genes. Table S2. Antimicrobial susceptibility for ESBL-positive E. coli blood isolates (n = 17). Table S3. Antimicrobial susceptibility for ESBL-positive E. coli urine isolates (n = 58). Figure S1. Cluster analysis of ESBL-positive E. coli (n = 75) isolates based on ERIC-PCR fingerprinting patterns using Jacquard index and UPGMA clustering. The scale at the top left represents percentage similarity. Isolate columns: identification with origins in brackets: O = outpatient, P = paediatrics, M = medicine, S = surgery, U = urine and B = blood. Presence (+) or absence (−) of blaCTX-M and sequence type are also indicated for each strain.
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Three new complexes, [(η<sup>6</sup>-C<sub>6</sub>H<sub>6</sub>)RuCl(C<sub>5</sub>H<sub>4</sub>N-2-CH=N-Ar)]PF<sub>6</sub> (Ar = phenylmethylene... more
Three new complexes, [(η<sup>6</sup>-C<sub>6</sub>H<sub>6</sub>)RuCl(C<sub>5</sub>H<sub>4</sub>N-2-CH=N-Ar)]PF<sub>6</sub> (Ar = phenylmethylene (<b>1</b>), (4-methoxyphenyl)methylene (<b>2</b>), phenylhydrazone (<b>3</b>)), are prepared by reacting [(η<sup>6</sup>-C<sub>6</sub>H<sub>6</sub>)Ru(μ-Cl)Cl]<sub>2</sub> with N,Nʹ-bidentate ligands in a 1%3A2 ratio. Full characterization of the complexes was accomplished using <sup>1</sup>H and <sup>13</sup>C NMR, elemental and thermal analyses, UV-Vis and IR spectroscopy and single crystal X-ray structures. Single crystal structures confirmed a pseudo-octahedral three-legged, piano-stool geometry around Ru(II), with the ligand coordinated to the ruthenium(II) through two N atoms. The cytotoxicity of the mononuclear complexes was established against the human ov...
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely... more
An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
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Research Interests: Microbiology, Environmental microbiology, Medical Microbiology, Biology, Mozambique, and 14 moreMolecular Microbiology, Medicine, Food Microbiology, Antibiotic Resistance, Colonization, Students, Klebsiella, Enterobacteriaceae, Clinical Sciences, Antibiotics, Ciprofloxacin, ESBL, E Coli, and Ceftazidime
Extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) represent a significant public health concern globally and are recognized by the World Health Organization as pathogens of critical priority. However, the prevalence of... more
Extended spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) represent a significant public health concern globally and are recognized by the World Health Organization as pathogens of critical priority. However, the prevalence of ESBL-PE in food animals and humans across the farm-to-plate continuum is yet to be elucidated in Sub-Saharan countries including Cameroon and South Africa. This work sought to determine the risk factors, carriage, antimicrobial resistance profiles and genetic relatedness of extended spectrum β-lactamase producing Enterobacteriaceae (ESBL-PE) amid pigs and abattoir workers in Cameroon and South Africa. ESBL-PE from pooled samples of 432 pigs and nasal and hand swabs of 82 humans were confirmed with VITEK 2 system. Genomic fingerprinting was performed by ERIC-PCR. Logistic regression (univariate and multivariate) analyses were carried out to identify risk factors for human ESBL-PE carriage using a questionnaire survey amongst abattoir workers. ESBL-PE...
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Senegalia nigrescens is used in traditional medicine for the treatment of dysentery and convulsions. This study was aimed at identifying bioactive compounds from S. nigrescens and carrying out in vitro and in silico anti-quorum sensing... more
Senegalia nigrescens is used in traditional medicine for the treatment of dysentery and convulsions. This study was aimed at identifying bioactive compounds from S. nigrescens and carrying out in vitro and in silico anti-quorum sensing studies on the compounds. Extracts of S. nigrescens were chromatographed repeatedly. The isolated compounds were characterised using NMR spectroscopy and mass spectrometry. The anti-quorum sensing potential of S. nigrescens crude extracts and selected phytochemicals was quantified using Chromobacterium violaceum quorum sensing-controlled violacein inhibition assays. Qualitative modulation of quorum sensing activity and signal synthesis was investigated using agar diffusion double ring assays and C. violaceum. Molecular docking was conducted to explore the binding conformations of ent-kaurene diterpenes and flavonoids into the binding sites of quorum sensing regulator proteins, CviR and CviR'. Phytochemical investigation of S. nigrescens resulted i...
Research Interests: Chemistry, Complementary and Alternative Medicine, Plant Biology, Ethnopharmacology, Medicinal Plants, and 15 moreFlavonoids, Medicine, Phytotherapy, Phytochemical, Acacia, Plant extracts, Quercetin, Protein Conformation, In Silico, Protein Binding, Chromobacterium, Chromobacterium violaceum, binding sites, Lupeol, and Pharmacology and pharmaceutical sciences
New complexes [(η6-p-cymene)Ru(C5H4N-2-CH=N–Ar)X]PF6 [X = Br (1), I (2); Ar = 4-fluorophenyl (a), 4-chlorophenyl (b), 4-bromophenyl (c), 4-iodophenyl (d), 2,5-dichlorophenyl (e)] were prepared, as well as 3a–3e (X = Cl) and the new... more
New complexes [(η6-p-cymene)Ru(C5H4N-2-CH=N–Ar)X]PF6 [X = Br (1), I (2); Ar = 4-fluorophenyl (a), 4-chlorophenyl (b), 4-bromophenyl (c), 4-iodophenyl (d), 2,5-dichlorophenyl (e)] were prepared, as well as 3a–3e (X = Cl) and the new complexes [(η6-arene)RuCl(N-N)]PF6 (arene = C6H5OCH2CH2OH, N-N = 2,2′-bipyridine (4), 2,6-(dimethylphenyl)-pyridin-2-yl-methylene amine (5), 2,6-(diisopropylphenyl)-pyridin-2-yl-methylene amine (6); arene = p-cymene, N-N = 4-(aminophenyl)-pyridin-2-yl-methylene amine (7)]. X-ray diffraction studies were performed for 1a, 1b, 1c, 1d, 2b, 5, and 7. Cytotoxicities of 1a–1d and 2 were established versus human cancer cells epithelial colorectal adenocarcinoma (Caco-2) (IC50: 35.8–631.0 μM), breast adenocarcinoma (MCF7) (IC50: 36.3–128.8.0 μM), and hepatocellular carcinoma (HepG2) (IC50: 60.6–439.8 μM), 3a–3e were tested against HepG2 and Caco-2, and 4–7 were tested against Caco-2. 1–7 were tested against non-cancerous human epithelial kidney cells. 1 and 2 were more selective towards tumor cells than the anticancer drug 5-fluorouracil (5-FU), but 3a–3e (X = Cl) were not selective. 1 and 2 had good activity against MCF7, some with lower IC50 than 5-FU. Complexes with X = Br or I had moderate activity against Caco-2 and HepG2, but those with Cl were inactive. Antibacterial activities of 1a, 2b, 3a, and 7 were tested against antibacterial susceptible and resistant Gram-negative and -positive bacteria. 1a, 2b, and 3a showed activity against methicillin-resistant S. aureus (MIC = 31–2000 μg·mL–1).
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Antibacterial compounds and metals co-select for antimicrobial resistance when bacteria harbour resistance genes towards both types of compounds, facilitating the proliferation and evolution of antimicrobial and heavy metal resistance.... more
Antibacterial compounds and metals co-select for antimicrobial resistance when bacteria harbour resistance genes towards both types of compounds, facilitating the proliferation and evolution of antimicrobial and heavy metal resistance. Antimicrobial and heavy metal resistance indices of 42 Gram-negative bacteria from a tilapia aquaculture system were determined to identify possible correlations between these phenotypes. Agar dilution assays were carried out to determine susceptibility to cadmium, copper, lead, mercury, chromate and zinc, while susceptibility to 21 antimicrobial agents was investigated by disk diffusion assays. Presence of merA, the mercury resistance gene, was determined by dot-blot hybridizations and PCR. Association of mercury resistance with integrons and transposon Tn21 was also investigated by PCR. Isolates displayed a high frequency of antimicrobial (erythromycin: 100%; ampicillin: 85%; trimethoprim: 78%) and heavy metal (Zn2+: 95%; Cd2+: 91%) resistance. No correlation was established between heavy metal and multiple antibiotic resistance indices. Significant positive correlations were observed between heavy metal resistance profiles, indices, Cu2+ and Cr3+ resistance with erythromycin resistance. Significant positive correlations were observed between merA (24%)/Tn21 (24%) presence and heavy metal resistance profiles and indices; however, significant negative correlations were obtained between integron-associated qacE∆1 (43%) and sulI (26%) gene presence and heavy metal resistance indices. Heavy metal and antimicrobial agents co-select for resistance, with fish-associated, resistant bacteria demonstrating simultaneous heavy metal resistance. Thus, care should be taken when using anti-fouling heavy metals as feed additives in aquaculture facilities.
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Abstract Three new complexes, [(η6-C6H6)RuCl(C5H4N-2-CH=N-Ar)]PF6 (Ar = phenylmethylene (1), (4-methoxyphenyl)methylene (2), and phenylhydrazone (3)), were prepared by reacting [(η6-C6H6)Ru(μ-Cl)Cl]2 with N,N′-bidentate ligands in a 1 : 2... more
Abstract Three new complexes, [(η6-C6H6)RuCl(C5H4N-2-CH=N-Ar)]PF6 (Ar = phenylmethylene (1), (4-methoxyphenyl)methylene (2), and phenylhydrazone (3)), were prepared by reacting [(η6-C6H6)Ru(μ-Cl)Cl]2 with N,N′-bidentate ligands in a 1 : 2 ratio. Full characterization of the complexes was accomplished using 1H and 13C NMR, elemental and thermal analyses, UV–vis and IR spectroscopy and single crystal X-ray structures. Single crystal structures confirmed a pseudo-octahedral three-legged, piano-stool geometry around Ru(II), with the ligand coordinated to the ruthenium(II) through two N atoms. The cytotoxicity of the mononuclear complexes was established against three human cancer cell lines and selectivity was also tested against non-cancerous human epithelial kidney (HEK 293) cells. The compounds were selective toward the tumor cells in contrast to the known anti-cancer drug 5-fluoro uracil which was not selective between the tumor cells and non-tumor cells. All the compounds showed moderate activity against MCF7 (human breast adenocarcinoma), but showed low antiproliferative activity against Caco-2 and HepG2. Also, antimicrobial activities of the complexes were tested against a panel of antimicrobial-susceptible and -resistant Gram-negative and Gram-positive bacteria. Of special interest is the anti-mycobacterial activity of all three synthesized complexes against Mycobacterium smegmatis, and bactericidal activity against resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus ATCC 43300.
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Research Interests: Chemistry, Natural Products, Biofilms, Biology, Flavonoids, and 15 moreMedicine, Biological Sciences, Escherichia coli, Phytochemical, Key words, Ficus, Antimicrobial, Clinical Sciences, CHEMICAL SCIENCES, Antibacterial activity, Plant extracts, Microbial Sensitivity Tests, Moraceae, Lupeol, and Medical and Health Sciences
Four eudesmanolide sesquiterpene lactones (1-4) were isolated from the aerial parts of Vernonia blumeoides used in Nigerian ethnomedicine for the treatment of diarrhea and malaria. Compound 1 demonstrated limited but interesting... more
Four eudesmanolide sesquiterpene lactones (1-4) were isolated from the aerial parts of Vernonia blumeoides used in Nigerian ethnomedicine for the treatment of diarrhea and malaria. Compound 1 demonstrated limited but interesting antibacterial activity against Bacillus, Staphylococcus and Streptococcus species. The crystal structure of 1 allowed the absolute configuration of the stereocentres in the molecule to be assigned.
Research Interests: Chemistry, Phytochemistry, Malaria, Nigeria, Medicine, and 12 moreMacromolecular X-Ray Crystallography, Diarrhea, Biological Sciences, Bacillus, Sesquiterpenes, CHEMICAL SCIENCES, Anti-Bacterial Agents, Microbial Sensitivity Tests, Molecular Conformation, Lactones, Molecular Structure, and Medical and Health Sciences
Bacteriophage T7 gene 17.5 coding for the only known holin is one of the components of its lysis system, but the holin activity in T7 is more complex than a single gene, and evidence points to the existence of additional T7 genes with... more
Bacteriophage T7 gene 17.5 coding for the only known holin is one of the components of its lysis system, but the holin activity in T7 is more complex than a single gene, and evidence points to the existence of additional T7 genes with holin activity. In this study, a T7 phage with a gene 17.5 deletion (T7-△holin) was rescued and its biological characteristics and effect on cell lysis were determined. Furthermore, the genomic evolution of mutant phage T7-△holin during serial passage was assessed by whole-genome sequencing analysis. It was observed that deletion of gene 17.5 from phage T7 delays lysis time and enlarges the phage burst size; however, this biological characteristic recovered to normal lysis levels during serial passage. Scanning electron microscopy showed that the two opposite ends of E. coli BL21 cells swell post-T7-△holin infection rather than drilling holes on cell membrane when compared with T7 wild-type infection. No visible progeny phage particle accumulation was ...
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Calvina E. L. Estaleva Hospital Central de Maputo Tomas F. Zimba Hospital Central de Maputo John Osei Sekyere University of KwaZulu-Natal College of Health Sciences Usha Govinden University of KwaZulu-Natal College of Health Sciences Ha... more
Calvina E. L. Estaleva Hospital Central de Maputo Tomas F. Zimba Hospital Central de Maputo John Osei Sekyere University of KwaZulu-Natal College of Health Sciences Usha Govinden University of KwaZulu-Natal College of Health Sciences Ha zah Y. Chenia University of KwaZulu-Natal College of Health Sciences Gunnar S. Simonsen Universitetssykehuset Nord-Norge Bjørg Haldorsen Universitetssykehuset Nord-Norge Sabiha Y. Essack University of KwaZulu-Natal College of Health Sciences Arn nn Sundsfjord ( arn nn.sundsfjord@uit.no ) UiT Norges arktiske universitet https://orcid.org/0000-0002-3728-2270
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Flavobacterium johnsoniae-like isolates play a major role in disease of farmed fish in South Africa [1]. F. johnsoniae-like isolates are known to form biofilms [2], which allows for a saprophytic mode of existence [3] and persistence in... more
Flavobacterium johnsoniae-like isolates play a major role in disease of farmed fish in South Africa [1]. F. johnsoniae-like isolates are known to form biofilms [2], which allows for a saprophytic mode of existence [3] and persistence in aquaculture systems. The persistance of the pathogenic Flavobacterium spp. in aquaculture tanks results in recurrent disease outbreaks causing high mortality and large economic losses. The pathogenicity and persistence of F. johnsoniae-like isolates associated with outbreaks of fish disease in South Africa is linked to their biofilm-forming ability, which facilitates their survival in aquaculture systems [2]. By understanding the stages of biofilm formation, mechanisms involved in biofilm formation and biofilm physiology, different strategies may be applied to eliminate biofilms. These strategies include the use of matrix-degrading enzymes, quorum-sensing inhibitors, phage inducers, bacteriophages, sugars, etc [4]. In order to effectively remove thes...
Four pentacyclic oleanane triterpenes (β-amyrin, methyl oleanolate, oleanolic acid and 3β-hydroxyolean-11-en-28,13β-olide) were isolated from the fruits of Carissa macrocarpawhilst the ursane triterpene, ursolic acid, was isolated from... more
Four pentacyclic oleanane triterpenes (β-amyrin, methyl oleanolate, oleanolic acid and 3β-hydroxyolean-11-en-28,13β-olide) were isolated from the fruits of Carissa macrocarpawhilst the ursane triterpene, ursolic acid, was isolated from the leaves. 3 β-hydroxyolean-11-en-28,13β-olide has only been found once previously (in the Lamiaceae) and its lactone ring, which contributes significantly to the expression of antibacterial activity in oleanane triterpenes, makes it an interesting molecule for synthetic and biological studies. The immune boosting properties of the triterpene rich edible fruits of C. macrocarpa are important, especially in South Africa, due to high incidences of Human immunodeficiency virus (HIV) and hepatitis in this country. Key words: Carissa macrocarpa, amatungula, oleanane triterpenes, ursolic acid.
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Abstract New osmium(II)-arene complexes [(η6-C6H6)OsCl(C5H4N-2-CH=N-C6H5X)](PF6) (X = p-flouro (1), p-chloro (2), p-methyl (3)) were synthesized by reaction of the corresponding bidentate N,N′-ligands with the osmium-arene precursor... more
Abstract New osmium(II)-arene complexes [(η6-C6H6)OsCl(C5H4N-2-CH=N-C6H5X)](PF6) (X = p-flouro (1), p-chloro (2), p-methyl (3)) were synthesized by reaction of the corresponding bidentate N,N′-ligands with the osmium-arene precursor [(η6-C6H6)Os(μ-Cl)Cl]2 in a 2:1 ratio. These complexes were characterized by UV–Vis, IR, 1H, 13C NMR spectroscopy, and elemental analysis and, for compound 1, a single crystal X-ray structure was also obtained. The complexes were investigated for antiproliferative activity in vitro against MCF-7 (human breast adenocarcinoma), Caco-2 (human epithelial colorectal adenocarcinoma), and HepG2 (human hepatocellular carcinoma) tumor cell lines. To test their selectivity, the non-tumor HEK293 (human embryonic kidney) cell line was used. The compounds were selective toward the tumor cell lines when compared to the known anticancer drug 5-fluorouracil which displayed low selectivity. The compounds were substantially more active against Caco-2 than 5-fluorouracil. They also showed moderate activity against the other two tumor cell lines. In addition, the antimicrobial activity of complex 2 was explored against a panel of antimicrobial-susceptible and -resistant Gram-negative and Gram-positive bacteria. Complex 2 showed anti-mycobacterial activity against Mycobacterium smegmatis and bactericidal activity against drug-resistant Enterococcus faecalis and methicillin-resistant Staphylococcus aureus ATCC 43300.
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The reaction of the ruthenium arene dimers [(η6-arene)Ru(μ-Cl)Cl]2 (where arene=benzene or p-cymene) with the ligands 4-benzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L1),... more
The reaction of the ruthenium arene dimers [(η6-arene)Ru(μ-Cl)Cl]2 (where arene=benzene or p-cymene) with the ligands 4-benzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L1), 2-methoxybenzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L2), 4-methylbenzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L3) and indole-3-carbaldehyde-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L4) in a 1:2 ratio gives the new complexes [(η6-arene)RuCl(L)]+ [arene=C6H6 (with L=L1(1), L2(3), L4(7), with PF6− as a counter ion, and L4 (6), with Cl− as a counter ion) or p-cymene with L=L1(2), L2(4), L3(5), L4(8) with PF6− as a counter ion]. All complexes were fully characterized using 1H and 13C NMR, elemental analyses, UV/Vis and IR spectroscopy. The single crystal X-ray structures of ligand L2 and complex 1 have been determined. The structure of 1 has the Ru atom coordinated with the arene group and to the N,N′-bidentate ligand and to the Cl atom. The arene group occupies the apex, while the ligan...
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Background Epidemiological data of cephalosporin-resistant Enterobacterales in Sub-Saharan Africa is still restricted, and in particular in Mozambique. The aim of this study was to detect and characterize extended-spectrum β-lactamase... more
Background Epidemiological data of cephalosporin-resistant Enterobacterales in Sub-Saharan Africa is still restricted, and in particular in Mozambique. The aim of this study was to detect and characterize extended-spectrum β-lactamase (ESBL) - and plasmid-mediated AmpC (pAmpC)-producing clinical strains of Escherichia coli at Maputo Central Hospital (MCH), a 1,000-bed reference hospital in Maputo, Mozambique. Methods A total of 230 clinical isolates of E. coli (n=230) from urine (n=199) and blood cultures (n=31) were collected at MCH during August-November 2015. Antimicrobial susceptibility testing was performed by the disc diffusion method and interpreted according to EUCAST guidelines. Isolates with reduced susceptibility to 3rd generation cephalosporins were examined further; phenotypically for an ESBL-/AmpC-phenotype by combined disc methods and genetically for ESBL- and pAmpC-encoding genes by PCR and partial amplicon sequencing as well as genetic relatedness by ERIC-PCR. Resul...
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The increased use of antibiotics in food animals has resulted in the selection of drug-resistant bacteria across the farm-to-fork continuum. This study aimed to investigate the molecular epidemiology of antibiotic-resistant Escherichia... more
The increased use of antibiotics in food animals has resulted in the selection of drug-resistant bacteria across the farm-to-fork continuum. This study aimed to investigate the molecular epidemiology of antibiotic-resistant Escherichia coli from intensively produced poultry in the uMgungundlovu District, KwaZulu-Natal, South Africa. Samples were collected weekly between August and September 2017 from hatching to final retail products. E. coli was isolated on eosin methylene blue agar, identified biochemically, and confirmed using polymerase chain reaction (PCR). Susceptibility to 19 antibiotics was ascertained by the Kirby–Bauer disc diffusion method. PCR was used to test for resistance genes. The clonal similarity was investigated using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR). In total, 266 E. coli isolates were obtained from all the samples, with 67.3% being non-susceptible to at least one antibiotic tested and 6.7% multidrug resistant....
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Providencia rettgeri is an opportunistic pathogen implicated in various clinical infections. Here, we report the genome sequence of a Providencia rettgeri strain isolated from hospital effluent in South Africa, which harbors the New Delhi... more
Providencia rettgeri is an opportunistic pathogen implicated in various clinical infections. Here, we report the genome sequence of a Providencia rettgeri strain isolated from hospital effluent in South Africa, which harbors the New Delhi metallo-β-lactamase (NDM) variant 18 gene (blaNDM-18). The 4,835,047-bp genome encodes a resistome and virulome that are of cardinal importance to Providencia infections.
Background: In recent years, the world has seen a surge in Enterobacteriaceae resistant to broad-spectrum beta-lactam antibiotics due to the production of extended-spectrum beta-lactamases (ESBLs) or plasmid-mediated AmpC (pAmpC) enzymes.... more
Background: In recent years, the world has seen a surge in Enterobacteriaceae resistant to broad-spectrum beta-lactam antibiotics due to the production of extended-spectrum beta-lactamases (ESBLs) or plasmid-mediated AmpC (pAmpC) enzymes. Data on the epidemiology of cephalosporin-resistant Enterobacteriaceae in Sub-Saharan Africa are still limited. Methods: Two hundred seventy-five non-repetitive stool samples were collected from Mozambican university students of both sexes. Samples were cultured on MacConkey agar with and without ceftriaxone (1 mg/L) for selection of third-generation cephalosporin-resistant isolates, which were subjected to antimicrobial susceptibility testing by disc diffusion, characterization of resistance genes by PCR and ERIC-PCR analysis for strain clonality.
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Bacterial resistance to antimicrobial drugs is a significant threat to humans and requires urgent intervention. There is, therefore, a clear need for the development of new types of antibacterial agents. We have thus synthesized the a,a... more
Bacterial resistance to antimicrobial drugs is a significant threat to humans and requires urgent intervention. There is, therefore, a clear need for the development of new types of antibacterial agents. We have thus synthesized the a,a 0-diaminoalkane-bridged diruthenium complex salts [Rp 2 NH 2 (CH 2) n NH 2 ]Y 2 (Rp ¼ CpRu(CO) 2 where Cp ¼ h 5 eC 5 H 5 ; n ¼ 2, 3, 4 and 6; Y ¼ BF 4 (1) or SO 3 CF 3 (2)) by the reaction of [RpNCCH 3 ]Y and NH 2 (CH 2) n NH 2 (n ¼ 2 (DAE) (3); n ¼ 3 (DAP) (4); n ¼ 4 (DAB) (5) and n ¼ 6 (DAH) (6 (BF) 4 , 7 (SO 3 CF 3)) at ambient temperature and pressure. These compounds are reported for the first time and have been fully characterized by infrared spectroscopy, 1 H and 13 C NMR spectroscopy, elemental analyses and melting points. The crystal structures of compounds 1 and 3 were obtained by single crystal X-ray crystallography. The two compounds crystallized in the mono-clinic crystal system in the P2 1 /n space group. Antimicrobial susceptibility tests were done for the new dinuclear complexes 3e7 as well as for mononuclear ruthenium complexes, [RpBA]BF 4 (8), [RpMBA]BF 4 (9), [RpMeOBA]BF 4 (10) and [RpAMBN]BF 4 (11) (BA¼ NH 2 CH 2 C 6 H 5 , MBA ¼ NH 2 CH(CH 3)C 6 H 5 , MeOBA ¼ NH 2 CH 2 C 6 H 4 OCH 3 and AMBN ¼ NH 2 CH 2 C 6 H 5) against selected drug-resistant and drug-susceptible Gram-positive and Gram-negative bacteria. Some of the dinuclear and mononuclear ruthenium complexes demonstrated good potential abilities to inhibit growth of the bacteria tested, with some showing better growth inhibition ability than well-known antibiotics such as ampicillin (AMP10). The ruthenium moiety CpRu(CO) 2 triggered or enhanced the ability of the coordinated ligands to inhibit bacterial growth. In vitro cytotoxicity of the complexes 8 and 10 was investigated through cell viability evaluation using human colorectal cancer (Caco-2) cells and the non-cancerous human em-bryonic kidney (HEK293) cells.
Fish infections caused by pathogenic Flavobacterium species are a major problem in the aquaculture industry worldwide, often leading to large economic losses. Thirty-two Flavobacterium spp. isolates, obtained from various diseased fish... more
Fish infections caused by pathogenic Flavobacterium species are a major problem in the aquaculture industry worldwide, often leading to large economic losses. Thirty-two Flavobacterium spp. isolates, obtained from various diseased fish species and biofilm growth, were charac-terised genetically using 16S rDNA PCR restriction fragment length polymorphism (RFLP), randomly amplified polymorphic DNA (RAPD) PCR, repetitive extragenic palindromic (REP) element PCR, plasmid profiling, whole cell protein (WCP) and outer membrane protein (OMP) analyses. Although the Flavobacterium spp. isolates displayed a high degree of genetic heterogeneity when differentiated by RAPD-PCR, REP-PCR and OMP fingerprinting techniques, isolates appeared very homogeneous by plasmid profiling and WCP analysis. No specific correlation was observed between the RAPD, REP and/or OMP profiles and fish host, site of isolation, geographic location or date of isolation of the Flavobacterium spp. isolates. Experimental infection of tilapia fish revealed variable levels of virulence and pathogenicity by isolates following handling stress and could not be linked to specific molecular types. This is the first reported isolation and characterisation of Flavo-bacterium johnsoniae-like spp. isolated from diseased fish in Southern Africa.
An increasing incidence of multidrug-resistant Aeromonas spp., which are both fish and emerging opportunistic human pathogens, has been observed worldwide. Quinolone–resistant Aeromonas spp. isolates are increasingly being observed in... more
An increasing incidence of multidrug-resistant Aeromonas spp., which are both fish and emerging opportunistic human pathogens, has been observed worldwide. Quinolone–resistant Aeromonas spp. isolates are increasingly being observed in clinical and environmental settings, and this has been attributed primarily to target gene alterations , efflux, and transferable quinolone resistance. Thirty-four Aeromonas spp., obtained from freshwater aquaculture systems, were screened for the presence of GyrA and ParC substitutions, efflux activity and the prevalence of plasmid-mediated quinolone resistance genes, qnr and aac-6′-Ib-cr. Although 44% of isolates were resistant to nalidixic acid, the majority were susceptible to ciprofloxacin and ofloxacin. The predominant GyrA substitution was Ser-83 → Val among Aeromonas veronii isolates whilst Aeromonas hydrophila isolates displayed a Ser-83 → Ile substitution, and Ser-80 → Ile substitutions were observed in ParC. Minimum inhibitory concentrations of fluoro(quinolones) were determined in the presence and absence of the efflux pump inhibitor, phenylalanine-arginine β-naphthylamide (PAβN). Addition of PAβN had no effect on the levels of fluoro(quinolone) resistance observed for these isolates. Although no aac-6′-Ib-cr variant genes were identified, qnrB and qnrS were detected for 41% and 24% of isolates, respectively, by Southern hybridization and confirmed by PCR and sequencing. Quin-olone resistance in these fish-associated Aeromonas isolates was related to mutations in the quinolone resistance determining regions of GyrA and ParC and presence of qnrB and qnrS. The presence of qnr alleles in Aeromonas spp. isolates may facilitate high-level fluoroquinolone resistance and potentially serve as reservoirs for the dissemination of qnr genes to other aquatic microbes.
The increasing incidence of multidrug-resistant Gram-negative bacterial pathogens has focused research on the suppression of bacterial virulence via quorum sensing inhibition strategies, rather than the conventional antimicrobial... more
The increasing incidence of multidrug-resistant Gram-negative bacterial pathogens has focused research on the suppression of bacterial virulence via quorum sensing inhibition strategies, rather than the conventional antimicrobial approach. The anti-virulence potential of eudesmanolide sesquiterpene lactones previously isolated from Vernonia blumeoides was assessed by inhibition of quorum sensing and in silico molecular docking. Inhibition of quorum sensing-controlled violacein production in Chromobacterium violaceum was quantified using violacein inhibition assays. Qualitative modulation of quorum sensing activity and signal synthesis was investigated using agar diffusion double ring assays and C. violaceum and Agrobacterium tumefaciens biosensor systems. Inhibition of violacein production was concentration dependent , with P90% inhibition being obtained with P2.4 mg ml À1 of crude extracts. Violacein inhibition was significant for the ethyl acetate extract with decreasing inhibition being observed with dichloromethane, hexane and methanol extracts. Violacein inhibition P80% was obtained with 0.071 mg ml À1 of blumeoidolide B in comparison with P3.6 mg ml À1 of blumeoidolide A. Agar diffusion double ring assays indicated that only the activity of the LuxI synthase homologue, CviI, was modulated by blumeoidolides A and B, and V. blumeoides crude extracts, suggesting that quorum sensing signal synthesis was down-regulated or competitively inhibited. Finally, molecular docking was conducted to explore the binding conformations of sesquiterpene lactones into the binding sites of quorum sensing regulator proteins, CviR and CviR 0. The computed binding energy data suggested that the blumeoidolides have a tendency to inhibit both CviR and CviR 0 with varying binding affinities. Vernonia eudesmanolide sesquiterpene lactones have the potential to be novel therapeutic agents, which might be important in reducing virulence and pathogenicity of drug-resistant bacteria in vivo.
Tetracycline-resistant bacteria are frequently isolated from aquaculture systems, where mobile resistance genes often transfer between bacteria associated with fish kept at high stocking densities. Bacterial isolates from an Oreochromis... more
Tetracycline-resistant bacteria are frequently isolated from aquaculture systems, where mobile resistance genes often transfer between bacteria associated with fish kept at high stocking densities. Bacterial isolates from an Oreochromis mossambicus (tilapia) aquaculture system (Stellenbosch, South Africa) were screened for their susceptibility to tetracycline. Genomic and plasmid DNA were used in PCR-RFLP assays employing six degenerate primer sets to identify the prevalence of nine tetracycline resistance genes. Isolates displaying a tet(A)-type tetracycline resistance gene were examined further for an association with transposon Tn1721. tet(A) was identified as the predominant tetracycline resistance determinant, followed by tet(B), -(E), and –(C) determinants. Isolates appeared to possess multiple tet genes simultaneously. Of the isolates presented with a tet(A) determinant, 73.9% appeared to be associated with Tn1721. No association between type of tetracycline resistance gene, ...
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Flavobacterium johnsoniae-like isolates are able to form biofilms and have been associated with disease outbreaks in fish. Surface colonization requires microbial adhesion strategies that are mediated by specific surface-associated... more
Flavobacterium johnsoniae-like isolates are able to form biofilms and have been associated with disease outbreaks in fish. Surface colonization requires microbial adhesion strategies that are mediated by specific surface-associated molecules. Blocking or inhibiting these molecules would facilitate the identification of adhesins involved in surface adherence and development of appropriate anti-adhesion strategies for F. johnsoniae-like isolates. Autoaggregation and adhesion assays were performed using F. johnsoniae-like isolates and Flavobacterium spp. type strains to determine the anti-adhesion effect of heat, proteinase K, glucose, galactose, mannose, and sodium metaperiodate. Majority of the isolates (~85%) displayed decreased autoaggregation following heat treatment, while ~80% and 100% of isolates demonstrated increased autoaggegation following proteinase K and sodium metaperiodate treatments. Although carbohydrate treatments increased autoaggregation indices, they were not sign...