The photodynamic therapeutic activities and optical limiting properties of metalated asymmetric porphyrins and corroles
- Authors: Burgess, Kristen Paige
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Photochemotherapy , Anti-infective agents , Nonlinear optics , Z-scan technique , Active oxygen , Time-dependent density functional theory , Chemical synthesis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424490 , vital:72158
- Description: Cancer is a devastating disease that is a leading cause of death worldwide. Despite the available cancer treatments, there is a significant need to improve the therapeutic approach towards this disease. Photodynamic therapy (PDT) is an alternative approach for treating cancer, which requires a photosensitiser, molecular oxygen and light. Although some porphyrin-based derivatives have been approved by the United States Food and Drug Administration (FDA) and other similar agencies elsewhere for photodynamic therapy, their relatively poor photophysicochemical properties mean that there is an ongoing need for new photosensitiser dyes. Singlet oxygen photosensitiser dyes can also be used to treat bacteria that develop antimicrobial resistance in the context of photodynamic antimicrobial chemotherapy (PACT). The main aim of this study was to synthesise and characterise a series of porphyrin dyes with 4-quinolinyl, thien-2-yl and 4-bromo-thien-2-yl meso-aryl groups and their Sn(IV) and In(III) complexes, as well as their corrole analogues. Corroles are contracted macrocycles that have interesting optical properties. The corroles selected for study were found to be difficult to synthesise and purify and had unfavourable photophysicochemical properties and were thus omitted from the PDT and PACT biological applications within this thesis. High- and low-symmetry A4 and ABAB type meso-tetraarylporphyrins porphyrins were synthesised to improve the photophysicochemical properties of the photosensitisers; the utility of these dyes as photosensitisers was studied against the MCF-7 breast cancer cell line for PDT and against Staphylococcus aureus and Escherichia coli for PACT. The thienyl-2-yl rings were introduced to red shift the lowest energy Q band towards the phototherapeutic window, while quaternisation of the nitrogen and sulfur atoms of the 4-quinolinyl and thien-2-yl rings to introduce a cationic nature was explored to improve the bioavailability of the drugs and uptake into the target cell walls for improved efficacy. Heavy Sn(IV) and In(III) central metal ions were introduced to enhance the singlet oxygen quantum yields and limit aggregation through axial ligation. The bromine atoms of the 4-bromo-thien-2-yl meso-aryl rings were also introduced to enhance the singlet oxygen quantum yields of the dyes. Furthermore, the utility of the porphyrin and corrole molecules for optical limiting properties to limit laser radiation to protect optical devices, including eyes, was explored by the z-scan technique. One of the dyes studied, Sn(IV) tetrathien-2-ylporphyrin, that exhibited the most favourable reverse saturable absorbance (RSA) response was embedded into a poly(bisphenol carbonate A) polymer thin film to further explore its suitability for practical applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Burgess, Kristen Paige
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Photochemotherapy , Anti-infective agents , Nonlinear optics , Z-scan technique , Active oxygen , Time-dependent density functional theory , Chemical synthesis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/424490 , vital:72158
- Description: Cancer is a devastating disease that is a leading cause of death worldwide. Despite the available cancer treatments, there is a significant need to improve the therapeutic approach towards this disease. Photodynamic therapy (PDT) is an alternative approach for treating cancer, which requires a photosensitiser, molecular oxygen and light. Although some porphyrin-based derivatives have been approved by the United States Food and Drug Administration (FDA) and other similar agencies elsewhere for photodynamic therapy, their relatively poor photophysicochemical properties mean that there is an ongoing need for new photosensitiser dyes. Singlet oxygen photosensitiser dyes can also be used to treat bacteria that develop antimicrobial resistance in the context of photodynamic antimicrobial chemotherapy (PACT). The main aim of this study was to synthesise and characterise a series of porphyrin dyes with 4-quinolinyl, thien-2-yl and 4-bromo-thien-2-yl meso-aryl groups and their Sn(IV) and In(III) complexes, as well as their corrole analogues. Corroles are contracted macrocycles that have interesting optical properties. The corroles selected for study were found to be difficult to synthesise and purify and had unfavourable photophysicochemical properties and were thus omitted from the PDT and PACT biological applications within this thesis. High- and low-symmetry A4 and ABAB type meso-tetraarylporphyrins porphyrins were synthesised to improve the photophysicochemical properties of the photosensitisers; the utility of these dyes as photosensitisers was studied against the MCF-7 breast cancer cell line for PDT and against Staphylococcus aureus and Escherichia coli for PACT. The thienyl-2-yl rings were introduced to red shift the lowest energy Q band towards the phototherapeutic window, while quaternisation of the nitrogen and sulfur atoms of the 4-quinolinyl and thien-2-yl rings to introduce a cationic nature was explored to improve the bioavailability of the drugs and uptake into the target cell walls for improved efficacy. Heavy Sn(IV) and In(III) central metal ions were introduced to enhance the singlet oxygen quantum yields and limit aggregation through axial ligation. The bromine atoms of the 4-bromo-thien-2-yl meso-aryl rings were also introduced to enhance the singlet oxygen quantum yields of the dyes. Furthermore, the utility of the porphyrin and corrole molecules for optical limiting properties to limit laser radiation to protect optical devices, including eyes, was explored by the z-scan technique. One of the dyes studied, Sn(IV) tetrathien-2-ylporphyrin, that exhibited the most favourable reverse saturable absorbance (RSA) response was embedded into a poly(bisphenol carbonate A) polymer thin film to further explore its suitability for practical applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
Phthalocyanine-nanoparticle conjugates supported on inorganic nanofibers as photocatalysts for the treatment of biological and organic pollutants as well as for hydrogen generation
- Authors: Mapukata, Sivuyisiwe
- Date: 2021-10-29
- Subjects: Phthalocyanines , Nanofibers , Nanoparticles , Zinc , Hydrogen , Organic water pollutants , Water Purification , Electrospinning , Photocatalysis , Photodegradation , Anti-infective agents
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192831 , vital:45268 , 10.21504/10962/192831
- Description: This thesis reports on the synthesis, photophysicochemical and photocatalytic properties of various zinc phthalocyanines (Pcs). For enhanced properties and catalyst support, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. For increased catalyst surface area and catalyst reusability, the Pcs and some of their conjugates were also supported on electrospun inorganic nanofibers i.e. SiO2, hematite (abbreviated Hem and has formula α-Fe2O3), ZnO and TiO2 nanofibers. The effect that the number of charges on a Pc has on its antimicrobial activities was evaluated by comparing the photoactivities of neutral, octacationic and hexadecacationic Pcs against S. aureus, E. coli and C. albicans. The extent of enhancement of their antimicrobial activities upon conjugation (through chemisorption) to Ag NPs was also studied in solution and when supported on SiO2 nanofibers. The results showed that the hexadecacationic complex 3 possessed the best antimicrobial activity against all three microorganisms, in solution and when supported on the SiO2 nanofibers. Covalent conjugation of Pcs with carboxylic acid moieties (complexes 4-6) to amine functionalised NPs (Cys-Ag, NH2-Fe3O4 and Cys-Fe3O4@Ag) resulted in enhanced singlet oxygen generation and thus antibacterial efficiencies. Comparison of the photodegradation efficiencies of semiconductor nanofibers (hematite, ZnO and TiO2) when bare and when modified with a Pc (complex 6) were evaluated. Modification of the nanofibers with the Pc resulted in enhanced photoactivities for the nanofibers with the hematite nanofibers being the best. Modification of the hematite nanofibers with two different Pcs i.e. monosubstituted (complex 5) and an asymmetrical tetrasubstituted Pc (complex 6) showed that complex 6 better enhanced the activity of the nanofibers. Evaluation of the hydrogen generation efficiencies of the bare and modified TiO2 nanofibers calcined at different temperatures demonstrated that the anatase nanofibers calcined at 500 oC possessed the best catalytic efficiency. The efficiency of the TiO2 nanofibers was enhanced in the presence of the Co and Pd NPs as well as a Pc (complex 7), with the extent of enhancement being the greatest for the nanofibers modified with the Pd NPs. The reported findings therefore demonstrate the versatility of applications of Pcs for different water purification techniques when supported on different nanomaterials. , Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Mapukata, Sivuyisiwe
- Date: 2021-10-29
- Subjects: Phthalocyanines , Nanofibers , Nanoparticles , Zinc , Hydrogen , Organic water pollutants , Water Purification , Electrospinning , Photocatalysis , Photodegradation , Anti-infective agents
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192831 , vital:45268 , 10.21504/10962/192831
- Description: This thesis reports on the synthesis, photophysicochemical and photocatalytic properties of various zinc phthalocyanines (Pcs). For enhanced properties and catalyst support, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. For increased catalyst surface area and catalyst reusability, the Pcs and some of their conjugates were also supported on electrospun inorganic nanofibers i.e. SiO2, hematite (abbreviated Hem and has formula α-Fe2O3), ZnO and TiO2 nanofibers. The effect that the number of charges on a Pc has on its antimicrobial activities was evaluated by comparing the photoactivities of neutral, octacationic and hexadecacationic Pcs against S. aureus, E. coli and C. albicans. The extent of enhancement of their antimicrobial activities upon conjugation (through chemisorption) to Ag NPs was also studied in solution and when supported on SiO2 nanofibers. The results showed that the hexadecacationic complex 3 possessed the best antimicrobial activity against all three microorganisms, in solution and when supported on the SiO2 nanofibers. Covalent conjugation of Pcs with carboxylic acid moieties (complexes 4-6) to amine functionalised NPs (Cys-Ag, NH2-Fe3O4 and Cys-Fe3O4@Ag) resulted in enhanced singlet oxygen generation and thus antibacterial efficiencies. Comparison of the photodegradation efficiencies of semiconductor nanofibers (hematite, ZnO and TiO2) when bare and when modified with a Pc (complex 6) were evaluated. Modification of the nanofibers with the Pc resulted in enhanced photoactivities for the nanofibers with the hematite nanofibers being the best. Modification of the hematite nanofibers with two different Pcs i.e. monosubstituted (complex 5) and an asymmetrical tetrasubstituted Pc (complex 6) showed that complex 6 better enhanced the activity of the nanofibers. Evaluation of the hydrogen generation efficiencies of the bare and modified TiO2 nanofibers calcined at different temperatures demonstrated that the anatase nanofibers calcined at 500 oC possessed the best catalytic efficiency. The efficiency of the TiO2 nanofibers was enhanced in the presence of the Co and Pd NPs as well as a Pc (complex 7), with the extent of enhancement being the greatest for the nanofibers modified with the Pd NPs. The reported findings therefore demonstrate the versatility of applications of Pcs for different water purification techniques when supported on different nanomaterials. , Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
The de novo biosynthesis of biotin is required for the optimal growth of Salmonella enterica serovar Typhimurium in the intracellular environment
- Authors: McLaughlin, Claire
- Date: 2021-10-29
- Subjects: Salmonella , Biotin , Biosynthesis , Salmonella typhimurium , Antibacterial agents , Anti-infective agents , Pathogenic bacteria , Salmonella food poisoning
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192097 , vital:45195
- Description: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a foodborne pathogen infecting humans and animals, contributing to significant morbidity and mortality worldwide each year. The increase in antibiotic-resistant S. Typhimurium infections in recent years has highlighted the need for new antibacterial drugs and drug targets. S. Typhimurium can acquire biotin through de novo biosynthesis or via transport from its extracellular environment. The importance of the vitamin for bacterial survival, coupled with the absence of the biotin biosynthetic pathway in humans, makes the biotin biosynthetic enzymes attractive targets for drug discovery. The study's primary aim was to determine the relative importance of the biotin biosynthesis and transport pathways for the in vitro and ex vivo growth and survival of S. Typhimurium, with the goal of validating the pathways as valid targets for antimicrobial drug development. In order to achieve this aim, we generated S. Typhimurium mutant strains harbouring deletions in either the biotin biosynthetic gene, bioB, or putative high-affinity biotin transporter, yigM (ΔbioB and ΔyigM, respectively), as well as a double mutant in which the two mutations were combined (ΔbioB ΔyigM). Since the simultaneous disruption of biotin biosynthesis and transport in the double mutant may form a synthetic lethal combination, preventing further analysis of the strain, we also constructed a conditional mutant in which the promoter of the yigM gene was replaced by the arabinose-regulatable, PBAD promoter in the ΔbioB background (ΔbioB PBAD::yigM). Since the expression of the YigM in this strain is arabinose-regulatable, its role as a biotin transporter can be evaluated by altering the arabinose concentration in the growth media. Once the mutant strains were isolated and verified genetically, their growth and that of their genetically complemented counterparts were analysed in liquid and/or solid M9 minimal medium in the absence of biotin. Consistent with previous observations, the ΔbioB auxotrophic mutant's growth was severely compromised in minimal media in the absence of biotin. The growth of the strain could, however, be restored by supplementation with exogenous biotin or expression of the wild type bioB gene from an episomal plasmid. The ability of biotin to reverse the growth defect of the ΔbioB mutant strain was, however, dependent on the presence of a functional YigM, since biotin supplementation did not affect the growth of the ΔbioB ΔyigM double mutant strain. The introduction of a second copy of the yigM gene in the ΔbioB ΔyigM background, however, restored the growth of the strain in the presence, but not absence, of biotin. The dependence of the double mutant on both YigM and biotin for growth supports the idea that the protein functions as the sole or primary biotin transporter in S. Typhimurium, as it has recently been shown for E. coli (Ringsletter, 2010; Finkenwirth et al, 2013). The essentiality of YigM for biotin transport was subsequently verified by two independent means. Firstly, the growth of the ΔbioB PBAD::yigM promoter-replacement mutant was strictly dependent on the inclusion of arabinose in biotin-supplemented M9 minimal media supplemented, indicating that the expression of YigM from the PBAD promoter is essential for biotin transport. Secondly, following treatment with a known small-molecule inhibitor of the biotin biosynthesis, MAC-13772, exogenous biotin was capable of restoring the growth defect of the YigM+ wild type S. Typhimurium strain, but not the YigM− ΔyigM mutant. Taken together, these findings confirm that YigM serves as the biotin transporter for S. Typhimurium and that the corresponding ΔyigM mutant is, as a result, defective for biotin transport. Having confirmed the genotypes and phenotypes of the ΔbioB, ΔyigM, and ΔbioB ΔyigM mutants, we next analysed the importance of the biotin biosynthesis and transport pathways for the growth and survival of S. Typhimurium within the intracellular environment. To this end, we determined the proliferation of each of the mutant strains following infection of HeLa epithelial and RAW264.7 macrophage-like cell lines. Our results revealed that the de novo biosynthesis of biotin is required for the optimal growth of S. Typhimurium following infection of both epithelial and macrophage-like cell lines. Disruption of biotin transport, by contrast, had no significant effect on the intracellular proliferation of S. Typhimurium when a functional pathway for the biosynthesis of biotin was present. The simultaneous disruption of biotin biosynthesis and transport, however, resulted in significant attenuation of S. Typhimurium in epithelial cells, while bacterial survival in macrophages decreased to below the limit of detection. Overall, our results suggest the S. Typhimurium relies primarily on biotin produced by the de novo biosynthesis pathway to support its growth in the intracellular environment. While YigM-mediated biotin transport is essential for sustaining the viability of intracellular S. Typhimurium in the absence of de novo biosynthesis, it appears to play a relatively minor role in the acquisition of biotin during growth in the nutrient-limited Salmonella containing vacuole. Our findings suggest that inhibiting biotin biosynthesis may be a viable strategy for combating systemic infections caused by Salmonella, as has been recently proposed for other medically important bacterial pathogens (Carfrae et al., 2020). , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: McLaughlin, Claire
- Date: 2021-10-29
- Subjects: Salmonella , Biotin , Biosynthesis , Salmonella typhimurium , Antibacterial agents , Anti-infective agents , Pathogenic bacteria , Salmonella food poisoning
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192097 , vital:45195
- Description: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a foodborne pathogen infecting humans and animals, contributing to significant morbidity and mortality worldwide each year. The increase in antibiotic-resistant S. Typhimurium infections in recent years has highlighted the need for new antibacterial drugs and drug targets. S. Typhimurium can acquire biotin through de novo biosynthesis or via transport from its extracellular environment. The importance of the vitamin for bacterial survival, coupled with the absence of the biotin biosynthetic pathway in humans, makes the biotin biosynthetic enzymes attractive targets for drug discovery. The study's primary aim was to determine the relative importance of the biotin biosynthesis and transport pathways for the in vitro and ex vivo growth and survival of S. Typhimurium, with the goal of validating the pathways as valid targets for antimicrobial drug development. In order to achieve this aim, we generated S. Typhimurium mutant strains harbouring deletions in either the biotin biosynthetic gene, bioB, or putative high-affinity biotin transporter, yigM (ΔbioB and ΔyigM, respectively), as well as a double mutant in which the two mutations were combined (ΔbioB ΔyigM). Since the simultaneous disruption of biotin biosynthesis and transport in the double mutant may form a synthetic lethal combination, preventing further analysis of the strain, we also constructed a conditional mutant in which the promoter of the yigM gene was replaced by the arabinose-regulatable, PBAD promoter in the ΔbioB background (ΔbioB PBAD::yigM). Since the expression of the YigM in this strain is arabinose-regulatable, its role as a biotin transporter can be evaluated by altering the arabinose concentration in the growth media. Once the mutant strains were isolated and verified genetically, their growth and that of their genetically complemented counterparts were analysed in liquid and/or solid M9 minimal medium in the absence of biotin. Consistent with previous observations, the ΔbioB auxotrophic mutant's growth was severely compromised in minimal media in the absence of biotin. The growth of the strain could, however, be restored by supplementation with exogenous biotin or expression of the wild type bioB gene from an episomal plasmid. The ability of biotin to reverse the growth defect of the ΔbioB mutant strain was, however, dependent on the presence of a functional YigM, since biotin supplementation did not affect the growth of the ΔbioB ΔyigM double mutant strain. The introduction of a second copy of the yigM gene in the ΔbioB ΔyigM background, however, restored the growth of the strain in the presence, but not absence, of biotin. The dependence of the double mutant on both YigM and biotin for growth supports the idea that the protein functions as the sole or primary biotin transporter in S. Typhimurium, as it has recently been shown for E. coli (Ringsletter, 2010; Finkenwirth et al, 2013). The essentiality of YigM for biotin transport was subsequently verified by two independent means. Firstly, the growth of the ΔbioB PBAD::yigM promoter-replacement mutant was strictly dependent on the inclusion of arabinose in biotin-supplemented M9 minimal media supplemented, indicating that the expression of YigM from the PBAD promoter is essential for biotin transport. Secondly, following treatment with a known small-molecule inhibitor of the biotin biosynthesis, MAC-13772, exogenous biotin was capable of restoring the growth defect of the YigM+ wild type S. Typhimurium strain, but not the YigM− ΔyigM mutant. Taken together, these findings confirm that YigM serves as the biotin transporter for S. Typhimurium and that the corresponding ΔyigM mutant is, as a result, defective for biotin transport. Having confirmed the genotypes and phenotypes of the ΔbioB, ΔyigM, and ΔbioB ΔyigM mutants, we next analysed the importance of the biotin biosynthesis and transport pathways for the growth and survival of S. Typhimurium within the intracellular environment. To this end, we determined the proliferation of each of the mutant strains following infection of HeLa epithelial and RAW264.7 macrophage-like cell lines. Our results revealed that the de novo biosynthesis of biotin is required for the optimal growth of S. Typhimurium following infection of both epithelial and macrophage-like cell lines. Disruption of biotin transport, by contrast, had no significant effect on the intracellular proliferation of S. Typhimurium when a functional pathway for the biosynthesis of biotin was present. The simultaneous disruption of biotin biosynthesis and transport, however, resulted in significant attenuation of S. Typhimurium in epithelial cells, while bacterial survival in macrophages decreased to below the limit of detection. Overall, our results suggest the S. Typhimurium relies primarily on biotin produced by the de novo biosynthesis pathway to support its growth in the intracellular environment. While YigM-mediated biotin transport is essential for sustaining the viability of intracellular S. Typhimurium in the absence of de novo biosynthesis, it appears to play a relatively minor role in the acquisition of biotin during growth in the nutrient-limited Salmonella containing vacuole. Our findings suggest that inhibiting biotin biosynthesis may be a viable strategy for combating systemic infections caused by Salmonella, as has been recently proposed for other medically important bacterial pathogens (Carfrae et al., 2020). , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Date Issued: 2021-10-29
Molecular characterization and antimicrobial resistance profiling of Salmonella species isolated from final effluent discharged from the Fort Hare Dairy Farm in Raymond Mhlaba Local Municipality
- Thinyane, Pindile https://orcid.org/0000-0001-8236-9407
- Authors: Thinyane, Pindile https://orcid.org/0000-0001-8236-9407
- Date: 2021-10
- Subjects: Salmonella typhimurium , Anti-infective agents , Multidrug resistance
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10353/22666 , vital:52618
- Description: The exposure of livestock to antimicrobials for treatment, prophylaxis, or development advancement can select for antimicrobial resistant organisms that can be transmitted to humans. Salmonella as a significant zoonotic microorganism can go about as a likely supply of antimicrobial resistant determinants. Salmonella is a zoonotic pathogen that causes food and waterborne infections. It affects wild and domestic animals, and humans, by causing a number of infections including Salmonellosis. Salmonella species infect humans through the consumption of contaminated meat, like beef, chicken, pork etc. This study aimed to determine the molecular characterization and antimicrobial resistance profile of Salmonella species isolated from effluent discharged from the Fort Hare Dairy Farm in Raymond Mhlaba Local Municipality. Polymerase chain reaction (PCR) was used for the molecular confirmation of the presumptive Salmonella isolates targeting both ompC gene and typh gene. Standard disc diffusion method was used for the antimicrobial susceptibility testing (AST) as recommended by the Clinical and Laboratory Standards Institute. The confirmed Salmonella isolates were tested against 12 test antimicrobial agents and were screened for antimicrobial resistance genes (ARGs) including blaTEM and amp for beta-lactams, and tetC for tetracycline. The research showed that the effluent discharge from this farm is contaminated with Salmonella. Presumptive Salmonella densities were ranging between 1,7 ×102 to 6,1×102 CFU/100ml, out of 83 presumptive isolates recovered, 61 were molecularly confirmed Salmonella typhimurium. The most prevalent Salmonella species found in this study was Salmonella typhimurium, which was more abundant in the final effluent discharges than in the water samples. This may be due to the contamination from farm animal faeces. The susceptibility against 12 different antibiotics by the recovered Salmonella typhimurium were examined, and Salmonella typhimurium isolates was notably resistant to azithromycin, ampicillin, amoxiclav, but less resistance were seen on doripenem , meropenem and ciprofloxacin but none of the isolates were resistant to norfloxacin. Antibiotic results obtained from this research suggest that Quinolones (Norfloxicin, Ciprofloxacin and Nalidixic acid), and Carbapenems (Meropenem and Doripenem.) were the most effective antibiotics against Salmonella. Forty-eight percent of isolates were found to be resistant to more than 3 antibiotics from different families thus considering them to be multidrug resistant. Resistant determinants ampC, blaTEM and tetC were detected on resistant isolates. Misuse and overuse of antibiotics on animal producing farms put human lives at risk as it promotes the emergency of multidrug resistant bacteria. Findings of this study revealed that animal producing farm pose a threat to the community as they harbour and promote the emergence of multidrug resistant Salmonella typhimurium. , Thesis (MSc) -- Faculty of Science and Agriculture, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Thinyane, Pindile https://orcid.org/0000-0001-8236-9407
- Date: 2021-10
- Subjects: Salmonella typhimurium , Anti-infective agents , Multidrug resistance
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10353/22666 , vital:52618
- Description: The exposure of livestock to antimicrobials for treatment, prophylaxis, or development advancement can select for antimicrobial resistant organisms that can be transmitted to humans. Salmonella as a significant zoonotic microorganism can go about as a likely supply of antimicrobial resistant determinants. Salmonella is a zoonotic pathogen that causes food and waterborne infections. It affects wild and domestic animals, and humans, by causing a number of infections including Salmonellosis. Salmonella species infect humans through the consumption of contaminated meat, like beef, chicken, pork etc. This study aimed to determine the molecular characterization and antimicrobial resistance profile of Salmonella species isolated from effluent discharged from the Fort Hare Dairy Farm in Raymond Mhlaba Local Municipality. Polymerase chain reaction (PCR) was used for the molecular confirmation of the presumptive Salmonella isolates targeting both ompC gene and typh gene. Standard disc diffusion method was used for the antimicrobial susceptibility testing (AST) as recommended by the Clinical and Laboratory Standards Institute. The confirmed Salmonella isolates were tested against 12 test antimicrobial agents and were screened for antimicrobial resistance genes (ARGs) including blaTEM and amp for beta-lactams, and tetC for tetracycline. The research showed that the effluent discharge from this farm is contaminated with Salmonella. Presumptive Salmonella densities were ranging between 1,7 ×102 to 6,1×102 CFU/100ml, out of 83 presumptive isolates recovered, 61 were molecularly confirmed Salmonella typhimurium. The most prevalent Salmonella species found in this study was Salmonella typhimurium, which was more abundant in the final effluent discharges than in the water samples. This may be due to the contamination from farm animal faeces. The susceptibility against 12 different antibiotics by the recovered Salmonella typhimurium were examined, and Salmonella typhimurium isolates was notably resistant to azithromycin, ampicillin, amoxiclav, but less resistance were seen on doripenem , meropenem and ciprofloxacin but none of the isolates were resistant to norfloxacin. Antibiotic results obtained from this research suggest that Quinolones (Norfloxicin, Ciprofloxacin and Nalidixic acid), and Carbapenems (Meropenem and Doripenem.) were the most effective antibiotics against Salmonella. Forty-eight percent of isolates were found to be resistant to more than 3 antibiotics from different families thus considering them to be multidrug resistant. Resistant determinants ampC, blaTEM and tetC were detected on resistant isolates. Misuse and overuse of antibiotics on animal producing farms put human lives at risk as it promotes the emergency of multidrug resistant bacteria. Findings of this study revealed that animal producing farm pose a threat to the community as they harbour and promote the emergence of multidrug resistant Salmonella typhimurium. , Thesis (MSc) -- Faculty of Science and Agriculture, 2021
- Full Text:
- Date Issued: 2021-10
Azadipyrromethenes for applications in photodynamic antimicrobial chemotherapy, photodynamic therapy and optical limiting
- Authors: Dubazana, Nadine
- Date: 2020
- Subjects: Dyes and dyeing -- Chemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Staphylococcus aureus , Nonlinear optics , Azadipyrromethenes , BODIPY
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166150 , vital:41333
- Description: Azadipyrromethenes, azaBODIPYs and zinc azadipyrromethene complexes were prepared and characterised to examine the effect on their photophysical properties of incorporating phenyl groups at the 1,3,5,7-positions with electron-donating and withdrawing groups at the para-positions. To enhance their ability to generate singlet oxygen, appropriate structural modifications were made through the addition of a Zn(II) ion or halogenation at the 2,6 positions. In vitro photodynamic therapy (PDT) studies targeting MCF-7 human breast cancer cells were carried out. To evaluate and understand the effectiveness of the dyes as photosensitisers, cellular uptake, phototoxicity and the half-maximal inhibitory concentration (IC50) values were analysed. Photodynamic antimicrobial chemotherapy (PACT) studies were also carried out to study the effectiveness of the dyes against Staphylococcus aureus (S. aureus). Dyes with donor-π-acceptor (D-π-A) properties were synthesised and tested against the second harmonic of the Nd:YAG laser in optical limiting (OL) studies. The second-order hyperpolarisability, third-order susceptibility and nonlinear absorption coefficient values were determined. The results suggest that 1,3,5,7-azaBODIPY dyes may be less suitable for use in this context than analogous D-π-A 3,5-distyrylBODIPY dyes. Molecular modelling was carried out to identify the structure-property relationships of the synthesised dyes by analysing trends in the energies of the frontier molecular orbitals (MOs) and spectroscopic properties.
- Full Text:
- Date Issued: 2020
- Authors: Dubazana, Nadine
- Date: 2020
- Subjects: Dyes and dyeing -- Chemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Staphylococcus aureus , Nonlinear optics , Azadipyrromethenes , BODIPY
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166150 , vital:41333
- Description: Azadipyrromethenes, azaBODIPYs and zinc azadipyrromethene complexes were prepared and characterised to examine the effect on their photophysical properties of incorporating phenyl groups at the 1,3,5,7-positions with electron-donating and withdrawing groups at the para-positions. To enhance their ability to generate singlet oxygen, appropriate structural modifications were made through the addition of a Zn(II) ion or halogenation at the 2,6 positions. In vitro photodynamic therapy (PDT) studies targeting MCF-7 human breast cancer cells were carried out. To evaluate and understand the effectiveness of the dyes as photosensitisers, cellular uptake, phototoxicity and the half-maximal inhibitory concentration (IC50) values were analysed. Photodynamic antimicrobial chemotherapy (PACT) studies were also carried out to study the effectiveness of the dyes against Staphylococcus aureus (S. aureus). Dyes with donor-π-acceptor (D-π-A) properties were synthesised and tested against the second harmonic of the Nd:YAG laser in optical limiting (OL) studies. The second-order hyperpolarisability, third-order susceptibility and nonlinear absorption coefficient values were determined. The results suggest that 1,3,5,7-azaBODIPY dyes may be less suitable for use in this context than analogous D-π-A 3,5-distyrylBODIPY dyes. Molecular modelling was carried out to identify the structure-property relationships of the synthesised dyes by analysing trends in the energies of the frontier molecular orbitals (MOs) and spectroscopic properties.
- Full Text:
- Date Issued: 2020
Composition and fate of triclosan in the sludge from wastewater treatment in Grahamstown, South Africa and Tiaret, Algeria
- Authors: Ncube, Mbonisi
- Date: 2017
- Subjects: Sewage sludge , Sewage Purification South Africa Grahamstown , Sewage Purification Algeria Tiaret , Sewage sludge as fertilizer , Anti-infective agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65156 , vital:28697
- Description: Physicochemical properties such as pH, specific surface area (SSA), cationic exchange capacity (CEC), loss on ignition (LOI), pathogens, plant nutrients (nitrates, ammonium and phosphates), and heavy metals (manganese, copper, lead and cadmium) were determined for sewage sludge from Grahamstown and Tiaret. The values obtained were log transformed thereafter a t-test at 5 % level of significance was used to test for the difference in each parameter for both sludges. The pH of sludge was determined in 1:3 water, 16 water, 1:3 0.01 M calcium chloride and 1:3 1 M potassium chloride. The pH for Grahamstown and Tiaret sludge were in the ranges of 6.66-7.11 and 7.88-8.18 respectively. The SSA values for Grahamstown and Tiaret were 218 ± 108 and 261 ± 99.9 m2/g, and the CEC values were 119 ± 2.09 and 136 ± 6.03 mEq/100, respectively. The LOI values obtained were 1.33 ± 0.03 and 1.48 ± 0.11 % for Grahamstown and Tiaret, respectively. E. coll and heterotrophic bacteria were the pathogens determined, and were extracted from sludge using sterile saline and nutrient broth. The concentration of E. coll in Grahamstown and Tiaret sludge were 468 ± 7.63 and 7769 ± 1268 CFU/g d.w and for heterotrophic bacteria were 1.17x109 ± 7.42x108 and 1.43x109 ± 9.11 x108 CFU/g d.w. For Grahamstown sludge, the concentration of nitrates, ammonium and phosphates were 55.61 ± 55.20 mg/g d.w, 6.60 ± 2.36 mg/g d.w and 1.40 ± 0.30 mg/g d.w, respectively. For Tiaret sludge, the concentration of nitrates, ammonium and phosphates were 2.56 ± 2.90 mg/g d.w, 0.64 ± 0.45 mg/g d.w and 0.24 ± 0.19 mg/g d.w, respectively. The concentration of Mn, Cu, Pb and Cd in Grahamstown sludge were 423 ± 101, 353 ± 92, 40.2 ± 20 and 0.0 mg/kg d.w respectively, and for Tiaret sludge, the corresponding concentrations were 358± 295, 549±50, 1427± 1352 and 1.54 ± 0.61 mg/kg d.w. Sewage sludge was found to contain Triclosan, and solubility studies of the compound were conducted using sodium deoxycholate and sodium lithocholate. The apparent solubilities and rate constants indicated in brackets of TCS at 37 °C were 35.4 ± 1.21 mg/L (1.28 ± 0.36 Hr-) and 14.4 ± 0.34 mg/L (0.99 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. The apparent solubilities and rate constants indicated in brackets of TCS at 15 °C were 32.3 ± 0.88 mg/L (2.16 ± 0.80 Hr-) and 14.2 ± 0.39 mg/L (1.02 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. Triclosan was extracted from sludge using 1 g/L sodium deoxycholate and the determined concentration were 142 ± 33.5 gg/g d.w for Grahamstown sludge and 0-12 gg/g d.w for Tiaret sludge. Finally plant growth studies were conducted on radish and garden cress plants using Grahamstown sludge at 0, 20, 40, 80 and 100 % treatments. Statistical analysis (t-test and Kruskal-Wallis) at 5 % level of significance was done to compare growth parameters between control and different sludge treatments. For radish plants, the values for plant height, root length, number of leaves, leaf length and dry mass were 28.4-80-7 mm, 4.3-44.7 mm, 3.3-17.0 mm, 2.3-4.0 leaves and 6.3-15.3 %, respectively. For garden cress, the values for plant height, root length, number of leaves, leaf length and dry mass were 13.7-25.0 mm, 7.7-20.3 mm, 5.7-8.3 leaves, 3.0-8.3 mm and 8.8-15.0 %, respectively. Twenty percent (20 %) sludge treatment gave the best results in radish and garden cress plants with respect to plant height, root length, number of leaves and dry mass. Triclosan concentration in radish and garden cress plants was below the detection limit of 32.4 gg/g d.w. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
- Authors: Ncube, Mbonisi
- Date: 2017
- Subjects: Sewage sludge , Sewage Purification South Africa Grahamstown , Sewage Purification Algeria Tiaret , Sewage sludge as fertilizer , Anti-infective agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65156 , vital:28697
- Description: Physicochemical properties such as pH, specific surface area (SSA), cationic exchange capacity (CEC), loss on ignition (LOI), pathogens, plant nutrients (nitrates, ammonium and phosphates), and heavy metals (manganese, copper, lead and cadmium) were determined for sewage sludge from Grahamstown and Tiaret. The values obtained were log transformed thereafter a t-test at 5 % level of significance was used to test for the difference in each parameter for both sludges. The pH of sludge was determined in 1:3 water, 16 water, 1:3 0.01 M calcium chloride and 1:3 1 M potassium chloride. The pH for Grahamstown and Tiaret sludge were in the ranges of 6.66-7.11 and 7.88-8.18 respectively. The SSA values for Grahamstown and Tiaret were 218 ± 108 and 261 ± 99.9 m2/g, and the CEC values were 119 ± 2.09 and 136 ± 6.03 mEq/100, respectively. The LOI values obtained were 1.33 ± 0.03 and 1.48 ± 0.11 % for Grahamstown and Tiaret, respectively. E. coll and heterotrophic bacteria were the pathogens determined, and were extracted from sludge using sterile saline and nutrient broth. The concentration of E. coll in Grahamstown and Tiaret sludge were 468 ± 7.63 and 7769 ± 1268 CFU/g d.w and for heterotrophic bacteria were 1.17x109 ± 7.42x108 and 1.43x109 ± 9.11 x108 CFU/g d.w. For Grahamstown sludge, the concentration of nitrates, ammonium and phosphates were 55.61 ± 55.20 mg/g d.w, 6.60 ± 2.36 mg/g d.w and 1.40 ± 0.30 mg/g d.w, respectively. For Tiaret sludge, the concentration of nitrates, ammonium and phosphates were 2.56 ± 2.90 mg/g d.w, 0.64 ± 0.45 mg/g d.w and 0.24 ± 0.19 mg/g d.w, respectively. The concentration of Mn, Cu, Pb and Cd in Grahamstown sludge were 423 ± 101, 353 ± 92, 40.2 ± 20 and 0.0 mg/kg d.w respectively, and for Tiaret sludge, the corresponding concentrations were 358± 295, 549±50, 1427± 1352 and 1.54 ± 0.61 mg/kg d.w. Sewage sludge was found to contain Triclosan, and solubility studies of the compound were conducted using sodium deoxycholate and sodium lithocholate. The apparent solubilities and rate constants indicated in brackets of TCS at 37 °C were 35.4 ± 1.21 mg/L (1.28 ± 0.36 Hr-) and 14.4 ± 0.34 mg/L (0.99 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. The apparent solubilities and rate constants indicated in brackets of TCS at 15 °C were 32.3 ± 0.88 mg/L (2.16 ± 0.80 Hr-) and 14.2 ± 0.39 mg/L (1.02 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. Triclosan was extracted from sludge using 1 g/L sodium deoxycholate and the determined concentration were 142 ± 33.5 gg/g d.w for Grahamstown sludge and 0-12 gg/g d.w for Tiaret sludge. Finally plant growth studies were conducted on radish and garden cress plants using Grahamstown sludge at 0, 20, 40, 80 and 100 % treatments. Statistical analysis (t-test and Kruskal-Wallis) at 5 % level of significance was done to compare growth parameters between control and different sludge treatments. For radish plants, the values for plant height, root length, number of leaves, leaf length and dry mass were 28.4-80-7 mm, 4.3-44.7 mm, 3.3-17.0 mm, 2.3-4.0 leaves and 6.3-15.3 %, respectively. For garden cress, the values for plant height, root length, number of leaves, leaf length and dry mass were 13.7-25.0 mm, 7.7-20.3 mm, 5.7-8.3 leaves, 3.0-8.3 mm and 8.8-15.0 %, respectively. Twenty percent (20 %) sludge treatment gave the best results in radish and garden cress plants with respect to plant height, root length, number of leaves and dry mass. Triclosan concentration in radish and garden cress plants was below the detection limit of 32.4 gg/g d.w. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Date Issued: 2017
- «
- ‹
- 1
- ›
- »