WHO has reported that antibiotic resistance is the third major cause of human death all over the globe. Recent study, has focused on the development of new antibacterial resistance drugs. Herein, we tried to synthesis a series of polymers that can mimic the HDPs. HDPs can target the bacterial cell membrane and they have less chances to develop bacterial resistance. We synthesized the amphiphilic polycarbonates that are highly selective to Gram-positive bacteria, including multidrug resistant pathogens. The membrane disruption activity of these polymers was proved by fluorescence and TEM studies and the drug resistance study showed that the polymers don’t develop bacterial resistance. In order to further design the molecules that can target a broad spectrum of bacteria, we have designed a series of lipidated dendrimers that can target the Gram-positive and Gram-negative bacteria. These dendrimers mimic the HDPs and target the bacterial cell membrane. Dendrimers are reported to inhibit the formation of bacterial biofilm which makes them promising for their future development of antibiotic agents. Apart from the synthesis of polymers and dendrimers as antibacterial agents, we have designed a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold and small dimeric cyclic guanidine derivatives. These molecules display good potency against a panel of multidrug-resistant Gram-positive and Gram-negative bacterial strains. Meanwhile, they also effectively inhibit the biofilm formation. Mechanistic studies suggest that these compounds kill bacteria by compromising bacterial membranes, a mechanism analogous to that of host-defense peptides (HDPs). Lastly, we also demonstrate that these molecules have excellent in vivo activity against MRSA in a rat model. This class of compounds could lead to an appealing class of antibiotic agents combating drug-resistant bacterial strains.

The emergence of antibiotic resistant bacteria has prompted the research into novel kinds of antibacterial small molecules and polymers. Nature has solved this issue with the use of cationic antimicrobial peptides, which act as nonspecific antibiotics against invading species. Herein, we have tried to mimic this general mechanism in a biocompatible and biodegradable polymer micelle based on the polymerization of naturally occurring amino acids lysine and phenylalanine linked to a PEG tether. This amphiphilic structure allows for the spontaneous collapse into stable nanoparticles in solution, which contains a hydrophilic outer layer and a hydrophobic core. Our polymers have shown activity against clinically relevant strains including Methicillin Resistant S. epidermidis, B. subtilis, K. pneumoniae, and P. aeruginosa. To further the application of our biopolymers, we have used them as drug delivery vehicles as well. First, we have used an anionic analogue based on glutamic acid to encapsulate a super hydrophobic drug Tanshinone IIA, and use it against a hepatoma bearing mouse model. Second, we have used a cationic analogue to form a complex with miRNA-139 and use it against a hepatoma bearing mouse model as well. In both cases, our PEG poly(amino acids)s have shown promising efficacy in drastically reducing the tumor size compared to the control only. Taken together, our results show that our nanoparticles have the potential to be versatile biomaterials as antibacterials as well as drug delivery vehicles in vivo.

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Ph.D. (Chemistry) / This study addressed the incorporation of nanotechnology-based materials, either through incorporating nanomaterials or by introducing nanostructures onto the membrane matrix, to form nano-enabled polymeric membranes with high specific flux and better anti-fouling profile. The aim of the study was to integrate nanotechnology and membrane science in order to improve the performance of water filtration membranes by alleviating some of the specific shortcomings of water treatment membranes......

Bacterial infections have posed a serious threat to the public health due to the significant rise of the infections caused by antibiotic-resistant bacteria. There has been considerable interest in the development of antimicrobial agents which mimic the natural HDPs, and among them biodegradable polymers are newly discovered drug candidates with ease of synthesis and low manufacture cost compared to synthetic host defense peptides. Herein, we present the synthesis of biocompatible and biodegradable polymers including polycarbonate polymers, unimolecular micelle hyperbranched polymers and dendrimers that mimic the antibacterial mechanism of HDPs by compromising bacterial cell membranes. The developed amphiphilic polycarbonates are highly selective to Gram-positive bacteria, including multidrug-resistant pathogens and the unimolecular micelle hyperbranched polymers showed promising broad-spectrum activity. However, lipidated amphiphilic dendrimers with low molecular weight display potent and selective antimicrobial activity against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. In addition to antibacterial activity against planktonic bacteria, these dendrimers were also shown to inhibit bacterial biofilms effectively. These class of polymers may lead to a useful generation of antibiotic agents with practical applications.

M.Tech. (Chemistry) / This work focused on the in-situ decoration of polyethersulfone (PES) nanofiber mats with silver nanoparticles (AgNPs) using an electrospinning technique. The biocidal and organic properties of the Ag decorated nanofibers were evaluated. Electrospinning of Ag decorated nanofibers was also carried out on a mixed matrix membrane support composed of nitrogen doped carbon nanotube (N-CNTs) and PES to fabricate a unique bi-faceted membrane. PES was dissolved in a solution containing silver nitrate (AgNO3) and N,Ndimethylacetamide (DMAc). The polymer solution was dissolved at 80ºC for 3 h under reflux until a yellow homogeneous solution was obtained which indicated the in-situ formation of AgNPs. The polymer solution was cooled and stored to remove air-bubbles. An ultraviolet - visible (UV – Vis) spectrometer was used to confirm the presence of AgNPs, while a Malvern nanosizer was used to estimate the size distribution of the AgNPs in the PES polymer matrix. The solution was electrospun on an aluminium (foil) collecting plate. Biocidal properties of the material were evaluated using Gram-positive (G+) Staphylococcus aureus (S. aureus) and ram-negative (G-) Escherichia coli (E. coli) by the zone inhibition method. The silver decorated polyethersulfone nanofibers showed good antibacterial activity against both G+ S. aureus and G- E. coli.

La prévention de la prolifération microbienne et de la formation de biofilms est une problématique qui touche tous les secteurs industriels. En particulier, le stockage d’hydrocarbures n’échappe pas à ce problème. Les revêtements des réservoirs de carburant sont ainsi recouverts de chrome (VI) afin d’augmenter l’adhérence du revêtement sur la surface métallique et d’offrir une protection efficace contre la corrosion électrochimique, et la corrosion microbienne induite par le développement microbien. Le chrome (VI) est toutefois très toxique, et fait partie des substances devant être retirées du marché par la réglementation européenne REACH. L’un des enjeux du projet SMILE, dans lequel s’inscrit cette thèse, vise à remplacer le chrome (VI) par des composés moins toxiques, mais tout aussi efficaces dans la prévention de la corrosion microbienne. Les travaux entrepris au cours de cette thèse avaient pour objectif l’élaboration de nano-particules polymères aux propriétés antimicrobiennes, leur incorporation dans un revêtement modèle, l’évaluation des propriétés antimicrobiennes des nano-particules seules et du système complet.Le deuxième chapitre est ainsi consacré à la synthèse et à l’évaluation des propriétés antimicrobiennes de biocides de type aminosucre, issus de ressources renouvelables. Dans le troisième chapitre est présentée la synthèse d’une première catégorie de nano-particules, agissant sur les micro-organismes par contact direct. Pour le second type de particules, présenté dans le quatrième chapitre, les nano-particules ont été conçues de manière à pouvoir libérer un biocide sous stimulus enzymatique microbien. L’incorporation, dans un revêtement modèle, des deux types de nano-particules précédemment préparés, a fait l’objet du chapitre cinq. Enfin, dans le dernier chapitre, les propriétés antimicrobiennes des deux familles de nano-particules ont été évaluées sur des souches fongiques du kérosène. / The prevention of microbial proliferation and biofilms formation affects every industrial field. In particular, the storage of hydrocarbons is highly concerned by this problem. The coatings of kerosene tanks contain chromium (VI) to increase the adhesion of the coating on the metallic surface and provide protection against electrochemical corrosion, as well as microbial corrosion induced by the development of microorganisms. Chromium (VI) is however very toxic, and is on the list of chemicals that have to be withdrawn from circulation by the european regulation REACH. The goal of the SMILE project, in which this thesis lies within, is to replace chromium (VI) by less toxic compounds that would be able to prevent microbial corrosion. The work undertaken during this thesis aimed at preparing antimicrobial polymeric nanoparticles, blending them in a coating and evaluating their antimicrobial properties, alone and in the coating.The second chapter is thus dedicated to the synthesis and evaluation of antimicrobial properties of aminosugar biocides, made from renewable ressources. In the third chapter is presented the synthesis of a first type of nanoparticles, that act on microorganisms by direct contact. For the second type of particles, presented in the fourth chapter, the nanoparticles have been designed so as to release a biocide under microbial enzymatic stimulus. The blending in a model coating of these two kinds of nanoparticles is described in the fifth chapter. In the last chapter, the antimicrobial properties of these two families of nanoparticles were evaluated against fungal strains known to proliferate in a kerosene medium.

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No description available.

Thesis (M.Sc.(Medical Sciences)) -- University of Limpopo, 2022 / Background: Wound infections continue to be problematic in clinical practice where empiric treatment of infections is a routine, with non-healing wounds being a burden to the health care system. A gap has been noted between antimicrobial resistance and demographic factors as an existing relationship. This necessitates an investigation of patterns of isolates and susceptibility profiles of microorganisms in wounds to modify the preventative and therapeutic strategies against the resistant strains leading to the stall of wound healing, which could aid in empiric treatment. Objective: The aim of this study was to determine the antimicrobial patterns and their associated demographic determinants in bacteria isolated from patients with non healing wounds at Pietersburg and Mankweng Hospitals, Limpopo Province. Methods: The study was conducted using antimicrobial susceptibility data collected from National Health Laboratory Service through Academic Affairs and Research Management System for the period 2016-2020. A total of 797 Antimicrobial Susceptibility Test results were analysed using Statistical Package for Social Sciences version 27.0. The susceptibility rates for the bacterial isolates by age and gender were calculated. The mean percentages for sensitivity and resistance were also calculated. Pearson’s Chi-square test was used to compare age and gender with drug susceptibility. A p-value of ≤ 0.05 was considered significant. Results: Of the 797 patient Antimicrobial Susceptibility Test results, 372 (46.7%) were males and 425 (53.3%) females, with mean age of 31.42 ± 21.75 years. The most common isolates were, Klebsiella pneumoniae (23%), Pseudomonas aeruginosa (21.7%), Escherichia coli (16%) and Proteus mirabilis (13.5%). Highest percentage of resistance to any antibiotic was amoxicillin, ampicillin (85.15%) then trimethoprim sulfamethoxazole (60.85%), amoxicillin ampicillin (49.1%), tigecycline (46.35%), cefepime (32.7%), gentamycin (25.4%), ciprofloxacin (22.5%), colistin (17.6%), and meropenem (12.3%). Furthermore, the general view of the study is no statistically clinical significance on the effect of age and gender on bacterial resistance although statistical significance was noted on age the resistance Acinetobacter baumannii vi (p=0.018), and gender on K. pneumoniae (p=0.015), P. mirabilis (p=0.024). Major resistance to A. baumannii, K. pneumoniae and P. mirabilis were from female patients. Conclusions: The most effective antibiotics were meropenem, colistin, and ciprofloxacin. The highest number of isolates were K. pneumoniae, E. coli, P. aeruginosa, P. mirabilis and A. baumannii with the most effective antibiotics gentamycin, meropenem, ciprofloxacin, and cefepime. Although the general view of the study is that no statistically clinical significance was noted on the effect of age and gender on bacterial resistance, it is important to note the significant observation that there was an observed relation of age to amoxicillin-clavulanic acid and Ciprofloxacin and gender to amoxicillin ampicillin. As such, there is insufficient evidence that supports the effect of age and gender on antimicrobial susceptibility. The study suggests caution against the use of amoxicillin ampicillin in the treatment of wound infections as it confers low levels of efficacy and high resistance and ultimately the call to revise minimum inhibitory concentrations and critical concentrations of all less effective drugs to increase their efficacy. / National Research Foundation (NRF)