The antibacterial potency of the extracts of the seed of Garcinia kola (bitter kola) was investigated in this study against a panel of referenced, environmental and clinical bacterial strains. The killing rates of the active extract as well as their potential for combination antibacterial therapy with standard antibiotics were also elucidated using standard procedures. The aqueous and acetone extracts of the seed were screened for activity against 27 bacterial isolates. The aqueous extract exhibited activity mainly against Gram positive organisms with Minimum inhibitory concentration (MIC) values ranging from 5 mgml-1 – 20 mgml-1, while the acetone extract showed activity against both Gram negative and Gram positive organisms with MIC values ranging from 10 mgml-1 - 0.156 mgml-1. The acetone extract also showed rapid bactericidal activity against Staphylococcus aureus ATCC 6538 with a 3.097 Log10 reduction in counts within 4 hours at 0.3125 mgml-1 and a 1.582 Log10 reduction against Proteus vulgaris CSIR 0030 at 5 mgml-1 after 1 hour. In addition, the aqueous, methanol and acetone extracts of the seeds also exhibited activity against four clinical strains of Staphylococcus isolated from wound sepsis specimens. The MIC values for the aqueous extract were 10 mgml-1 for all the isolates while the acetone and methanol extracts had lower values ranging from 0.3125 - 0.625 mgml-1. The acetone extract was strongly bactericidal against Staphylococcus aureus OKOH3 resulting in a 2.70 Log10 reduction in counts at 1.25 mgml-1 within 4 hours of exposure and a complete elimination of the organism after 8 hours. The bactericidal vi activity of the same extract against Staphylococcus aureus OKOH1 was weak, achieving only a 2.92 Log10 reduction in counts at 1.25 mgml-1 (4× MIC) in 24 hours. In the test for interactions between the acetone extract of the seeds and antibiotics, synergistic interactions were observed largely against Gram positive organisms using the FIC indices, (indices of 0.52 - 0.875) with combinations against Gram negatives yielding largely antagonistic interactions (indices of 2.0 to 5.0). Synergy (≥ 1000 times or ≥ 3 Log10 potentiation of the bactericidal activity) against both Gram negative and Gram positive organisms was detected by time kill assays mainly involving the antibiotics tetracycline, chloramphenicol, amoxycillin and penicillin G. Combinations involving erythromycin and ciprofloxacin consistently gave antagonistic or indifferent interactions. We conclude that the acetone extract of Garcinia kola seeds possess strong bactericidal activities against both Gram positive and Gram negative organisms and can be therapeutically useful in the treatment of bacterial infections including the problematic staphylococcal wound infections. In addition, the acetone extract can be a potential source of broad spectrum resistance modifying compounds that can potentially improve the performance of antibiotics in the treatment of drug resistant infections.

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The transition from unicellular to multicellular life is captivating because free-living individuals become complex, coordinated assemblages that display unique properties and behaviors. It is a transformative step in biology that optimizes survival and resource utilization, especially in fluctuating environments. In microbiology, this multicellular organization assumes an intriguing form known as biofilms. Bacterial biofilms, assemblages of cells encased in a self-produced matrix, are sophisticated structures that provide protection from environmental challenges. The emerging understanding of biofilms reveals that bacteria within them do not exist as passive, isolated entities. Instead, they display spatial organization, physiological differentiation, and even metabolic interactions such as cross-feeding. The pathogenic bacterium Pseudomonas aeruginosa, which is a common cause of biofilm-based infections and a popular model organism, has been shown to form metabolic subpopulations and differentially regulate gene expression across depth in biofilms. However, one open question is the nature of this cellular arrangement in P. aeruginosa biofilms, the mechanisms governing it, and its physiological ramifications. My thesis addresses the overarching question: Does cellular arrangement in P. aeruginosa biofilms influence nutrient distribution, metabolic activity, antibiotic tolerance, and metabolic cross feeding? Through the use of paraffin embedding, thin-sectioning, and confocal microscopy, I delve deep into the biofilm, particularly in the z-direction, byproducing high-resolution images that provide insights into the three-dimensional structure and dynamics of these bacterial communities. The first chapter, serving as the foundation of this exploration, provides an introduction of the principles of multicellularity. It draws attention to the hallmarks of multicellularity, encompassing metabolic cross-feeding, protective advantages, and labor specialization while also shedding light on its challenges. In the context of multicellularity, biofilms are introduced, emphasizing the formation of bacterial biofilms, their environmental and medical implications, and specifically highlighting the importance of P. aeruginosa biofilms for understanding microanatomy and physiology. Chapter 2 presents the crux of our exploration, underlining how cellular arrangement directly impacts metabolic activity and antibiotic tolerance in P. aeruginosa biofilms. A striking observation was the presence of vertical, clonal striations, suggesting the presence of an organized architecture within mature biofilms. Mutants with disordered cell arrangements, particularly in O-antigen attachment, showed altered patterns of nutrient distribution and metabolic activity in addition to distinct patterns of antibiotic- induced cell death. Such findings build on prior knowledge by illuminating the intricate relationships between biofilm anatomy, metabolic differentiation, and drug tolerance. Chapter 3 introduces the use of light-sheet microscopy for live imaging of pellicle biofilms, which offers a real-time window into biofilm development and cellular dynamics. In Chapter 4, the narrative takes a broader perspective, focusing on the influence of various carbon sources on cellular arrangement. It introduces the presence of metabolic cross-feeding among different biofilm subpopulations and hints at the potential relationship between cell arrangement and heterogeneous metabolic activity patterns. The work in this thesis reveals that the arrangement of cells within P. aeruginosa biofilms determines metabolic outcomes, antibiotic responses, and potential cross- feeding interactions. In a world where biofilm-related infections account for an alarming 80% of persistent bacterial infections, understanding biofilm microanatomy has implications for therapeutic strategies and possibly reshaping our battle against antibiotic tolerance. A more detailed picture of the relationship between cell arrangement, physiological differentiation, and metabolic cooperation within biofilms has the potential to provide inroads toward new approaches to combating these recalcitrant structures.

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Thesis (DPhil)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: In this dissertation, I grapple with the problem of global drug resistance and moral responsibility which, as far as I am aware, has so far not been presented as a topic of ethical inquiry. It represents a conundrum involving three major factors: microbial adaptation and change, human social factors and environmental changes. Drug resistance is a phenomenon in which certain microorganisms, when exposed to antimicrobial agents, may acquire the beneficial trait of drug resistance which ensures a better potential for their survival. The acquired trait of drug resistance I argue renders such microorganisms 'supra-natural '. Supra-natural is a term I coin for entities that have been imposed upon nature by human design; they do not follow the natural evolutionary processes of adaptation and change. Drug resistance is classified as an emerging infectious disease. Human social factors and environmental change (particularly population growth, density and consumerist practices) enhance the rise of emerging infectious diseases. Through such increasing destructive practices, stress is placed on the environment. Environmental stress facilitates the rise of new and old infectious diseases and the spread of drug resistant supra-natural microorganisms. Thus, our ability to treat successfully illnesses and injuries in humans, animals and plants is increasingly impaired. Morally, we are responsible for the problem of global drug resistance. Drug resistant microorganisms exist in nature and concerning this, we can do nothing. At best, we can only try to control the problem using prudential measures. The problem of global drug resistance represents both a biomedical ethical and an environmental ethical issue. Is there a way out of the human-nature debate? Through Bryan Norton's enlightened anthropocentrism, I identify the ways in which his thesis may be applied to the problem of human and environmental concerns and show its applicability in broadening the parameters of biomedical ethics education to include environmental concerns. / AFRIKAANSE OPSOMMING: In hierdie proefskrif bespreek ek die probleem van die verskynsel dat mikroorganismes op 'n globale skaal weerstand begin bied teen mediese middels (globale middel-weerstandigheid) en die morele verantwoordelikheid wat dit oproep - 'n probleem wat, na my beste wete, nog nooit aangebied is as 'n tema van etiesfilosofiese ondersoek nie. Dit verteenwoordig 'n kompleks van drie belangrike oorwegings: mikrobiese aanpassings en veranderinge, menslike sosiale faktore, en omgewingsveranderinge. Middel-weerstandigheid is 'n verskynsel waarin sekere mikro-organismes, wanneer hulle blootgestel word aan antimikrobiese agente, die (vir hulself) voordelige kenmerk kan bekom van weerstandigheid teen die middel; iets wat 'n beter potensiaal vir hul eie oorlewing verseker. Hierdie bekomde kenmerk (middel-weerstandigheid) maak, volgens my argument, sulke mikro-organismes 'supra-natuurlik'. Supra-natuurlik is 'n term wat ek munt vir entiteite wat aan die natuur blootgestel is as gevolg van menslike ontwerp; hulle volg nie die natuurlike evolusionêre prosesse van adaptasie en verandering nie. Middel-weerstandigheid word geklassifiseer as 'n opkomende aansteeklike siekte. Menslike sosiale faktore en omgewingsveranderinge (veral bevolkingsgroei, -digtheid and verbruikerspraktyke ) vergroot die opkoms van aansteeklike siektes. Deur sodanige toenemende destruktiewe praktyke word stres geplaas op die omgewing. Omgewingstres fasiliteer die opkoms van nuwe en ou aansteeklike siektes asook die verspreiding van weerstandige supra-natuurlike mikro-organismes. Ons vermoë om siektes en beserings van mense suksesvol te behandel, word gevolglik toenemend ondermyn. Moreel gesproke is ons verantwoordelik vir die probleem van globale middelweerstandigheid. Middel-weerstandige mikro-organismes bestaan in die natuur, en aan daardie feit as sodanig kan ons niks doen nie. Ons kan, ten beste, probeer om die probleem te beheer deur middel van verstandige maatreëls. Die probleem van globale middel-weerstandigheid verteenwoordig sowel 'n biomedies-etiese as 'n omgewingsetiese kwessie. Is daar 'n uitweg uit die mens-natuur debat? Ek identifiseer, met 'n beroep op Bryan Norton se swak antroposentrisme, maniere waarop sy tese toegepas sou kon word op die probleem van menslike en omgewingsoorgwegings Ek wys ook op die toepaslikheid daarvan vir die verbreding van die parameters van biomediese etiek-opvoeding ten einde omgewingsoorwegings deel van 19.te maak.