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Nanomaterial’s applications have expanded greatly in the last few decades due to their interesting properties. Example of nanomaterials are metal nanoparticles NP. NP have interesting physical and optical properties that make them different and more useful than their bulk counterpart. Some of these properties are the large surface area to mass ratio and their ability to absorb light. NP have been applied in the health, environment, and catalysis fields The main focus of this thesis will be on the applications of nanomaterials in medicine and catalysis. In the first part of the thesis, coated polydispersed and polymorphic silver nanostructures AgNS were synthesized using seed mediated method. The synthesized AgNS were characterized using SEM, TEM, and UV-VIS. The stability of these AgNS were determined by measuring the shift in the plasmon band over time and by measuring their zeta potential. Moreover, the bactericidal properties of coated AgNS were tested on gram negative bacteria such as Escherichia coli and Pseudomonas aeruginosa and gram positive bacteria such as Methicillin- Resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus. The second part of the thesis discusses the field of nanocatalysis where different supported metal nanoparticles on TiO2 were synthesized and characterized by TEM, diffuse reflectance DR, XPS and ICP. The activity of the synthesized catalysts was tested for Ullmann C-C cross coupling reaction. The use of the photoresponisve Pd@TiO2 under the combination of UVA 368 and visible light 465nm irradiation offered the highest selectivity toward the cross coupling product.

L’émergence des bactéries résistantes aux béta-lactamines et aux carbapénèmes, a abouti à la réintroduction de la colistine comme agent de dernier recours pour traiter les infections dues à ces germes. Cependant, les résistances chromosomique et plus récemment plasmidique à la colistine ont apparu. Ce problème de bactéries multi-résistantes a par la suite déclenché la publication d’articles alarmants sur les dangers de ces germes. Pour répondre à la dramatisation médiatique liée à ce problème, mon projet de thèse vise à proposer des stratégies thérapeutiques pour traiter les infections dues aux bactéries multi-résistantes. Dans un premier temps, nous avons testé l’activité d’un large panel comprenant des anciens antibiotiques contre les bactéries résistantes aux carbapénèmes et d’autres résistantes à la colistine. Plusieurs familles d’antibiotiques ont été efficaces contre ces 2 types de bactéries résistantes.Dans un deuxième temps, nous avons évalué l’activité d’antibiotiques combinés en vue de détecter une synergie d’action. Deux combinaisons synergiques ont été retenues : colistine + sulfadiazine et colistine + acide fusidique. Ces associations d’antibiotiques ont démontré un effet bactéricide sur une collection de bactéries Gram négatives résistantes à la colistine, et ceci indépendamment du mécanisme de résistance. / The emergence of beta-lactam and carbapenem resistant bacteria, resulted in the reintroduction of colistin as an agent of last resort to treat infections caused by these bacteria. However, chromosomal resistances and more recently plasmidic to colistin appeared. This problem of multidrug-resistant bacteria subsequently triggered the publication of alarming articles on the dangers of these germs. To answer the media dramatization related to this problem, my thesis project aims to propose therapeutic strategies to treat infections due to multiresistant bacteria.Initially, we tested the activity of a large panel including old antibiotics against carbapenem resistant bacteria and others resistant to colistin. Several families of antibiotics have been effective against these two types of resistant bacteria.In a second step, we evaluated the activity of combined antibiotics in order to detect a synergistic action. Two synergistic combinations were retained: colistin + sulfadiazine and colistin + fusidic acid. These combinations of antibiotics have shown a bactericidal effect on a collection of Gram-negative colistin-resistant bacteria, independent of the resistance mechanism.

Antimicrobial (cationic) proteins play an important role in innate imunity. Such proteins can possess antibacterial, antiendotoxic or fungicidal abilities. The rising resistence of microbes to common antibiotics evokes acute need of studying more endogenous proteins to reveal new potential antibiotics. Ticks, the blood-feeding ectoparasites with effectual defense system, present an endless source of newly described and unknown antimicrobial peptides/proteins with significant theurapeutic potential. This study represents identification of histidine-rich proteins detected in Ixodes ricinus and Ixodes scapularis, that are related to recently described new family of proteins isolated from Rhipicephalus microplus (protein microplusin) and Amblyomma hebraeum (protein heraein). Analysis and characterization of newly identified histidine rich proteins, study of their antimicrobial and protease inhibitory effect are the main goals of this study.

Antimicrobial resistance and antimicrobial misuse are of global concern but affect more the resource-constrained settings. Limited research has been done in Peru in order to address these topics. We interviewed 256 physicians of two hospitals of Lima in order to assess the knowledge, attitudes, and practices about antimicrobial resistance and antimicrobials use. Most of them agreed that antimicrobial resistance is a problem worldwide and within Peru, but only 20% correctly estimated the level of resistance of Klebsiella pneumoniae to third generation cephalosporins. We also developed a network of nine hospitals in Lima to perform a resistance surveillance of key isolates causing bacteremia. We found during a one-year period that Staphylococcus aureus was the most frequently Gram positive isolated (22%). K. pneumoniae and Escherichia coli were the most frequent Gram-negative bacilli, >75% of both produced extended-spectrum β-lactamases (ESBLs). ESBL-producers microorganisms had also higher level of co-resistance to ciprofloxacin and gentamicin. Finally, to explore the antimicrobial resistance and molecular characteristics of methicillin-resistant S. aureus, we analyzed isolates from patients and healthcare workers (HCWs). Fifty percent of 338 blood isolates were methicillin-resistant (MRSA); one predominant multidrug-resistant MRSA strain was found in all hospitals (ST 5 spa t149-SCCmec I-, the Cordobes-Chilean clone. MRSA nasal carriage rate of 8.7%, was found among HCWs. The two most common clones circulating among HCWs were also the two predominant among patients with bacteremia. There is a need to implement cost-effective infection control policies to reduce the transmission of multidrug resistant microorganisms in these settings. / La résistance aux antibiotiques et leur utilisation inappropriée constituent un problème majeur de santé publique qui affecte particulièrement les pays à revenus faibles et intermédiaires. Les données concernant cette problématique sont très limitées au Pérou. Nous avons interrogé 256 médecins de deux hôpitaux à Lima afin d’évaluer leurs connaissances et leurs pratiques vis-à-vis de l’utilisation des antibiotiques et de la résistance aux antibiotiques. La plupart des médecins étaient conscientisés à la problématique de la multirésistance chez les entérobactéries, mais seulement 20% d’entre eux estimaient correctement le taux résistance de Klebsiella pneumoniae aux céphalosporines à large spectre au sein de leurs institutions. Au cours de ce travail, un réseau entre neuf hôpitaux de Lima a été implémenté afin de suivre la résistance aux antimicrobiens des souches isolées d’hémocultures. Au cours des années 2008-2009, le Staphylococcus aureus était la bactérie Gram-positive la plus fréquente (22%) ;K. pneumoniae et Escherichia coli représentaient les bactéries Gram-négatives les plus souvent isolées d’hémocultures. Parmi ces dernières entérobactéries, 75% produisaient des β-lactamases à spectre étendu (BLSE) avec un taux élevé de co- résistance à la ciprofloxacine et à la gentamicine. Les souches de S. aureus isolées d’hémocultures chez les patients hospitalisés et de dépistage chez les professionnels de santé (PS) ont été caractérisées pour leur profil de résistance aux antibiotiques et génotypées par biologie moléculaire. La moitié des 338 souches isolées d’hémocultures étaient résistantes à la méticilline (« MRSA ») et appartenaient à un clone prédominant disséminés dans ces différents hôpitaux, appelé le ST 5- spa t149-SCCmec I, ou le clone Cordobes-Chilien. Le taux de portage nasal de MRSA parmi les PS était à 8,7% ;les deux génotypes les plus fréquemment observés chez les PS appartenaient aux mêmes clones que ceux retrouvés majoritairement chez les patients hospitalisés. Cette observation suggère une transmission horizontale. L’implémentation de politiques de contrôle de l'infection est primordiale dans les établissements de santé au Pérou afin de réduire la transmission de micro-organismes multi-résistants. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

Magister Scientiae - MSc / Extracts from the root bark, stem bark, and leaves of R. natalensis were screened for antibacterial activity against standard bacterial strains; Staphylococcus aureas, Escherichia coli and Pseudomonas aureginosa, and fungi; Candida albicans, Trichophyton mentagrophytes or Microsporum gyseum. Chromatographic techniques were utilized to isolate pure compounds. This study validates and documents, in a systematic way, the antimicrobial properties of the R. natalensis used for many years by many people of the world. It also provides valuable information for further phytochemical isolation and characterization studies of active compounds, necessary for the development of new drugs. The extractions were carried out using broad spectrum of solvents (hexane, dichloromethane, ethyl acetate, and methanol). Fractionation was done using standard chromatographic techniques. A total of seven (7) compounds were isolated from R. natalensis. Three of the isolates were characterized and their structures were unambiguously established by detailed spectroscopic analysis that involved high resolution mass spectrometry, 1D and 2D-NMR spectral data experiments 1H, 13C, DEPT, COSY, HMBC, and NOESY. These compounds are: 3-(1-(2,4-dihydroxyphenyl)-3,3-bis(4- hydroxyphenyl)-1-oxopropan-2-yl)-7-methoxy- 4H-chromone-4-one (39), Rhuschromone, a novel compound isolated for the first time, 2’,4’-dihydroxychalcone-(4-O-5’’’)-4’’,2’’’,4’’’- trihydroxychalcone (40) and 3-((Z)-heptadec-13-enyl) benzene- 1,2-diol (41), an urushiol. Compound 39 recorded the highest activity zone of inhibition (21mm) against S. aureas, which was found to be 50% as active the chloramphenicol standard used. The traditional use of the extracts in infections and inflammatory conditions is rationalized based on the content of theisolated compounds, and it has been proposed that the total crude extract, with its contents of so many bioactive compounds, could be formulated for use in many infections, microbial or fungal. Furthermore, not all of the species studied to date have been fully characterized for potential bioactivities. Thus, there remains a significant research gap spanning the range from lead chemical discovery through process development and optimization in order to better understand the full bioactive potential of many of these plants. / South Africa

This study was performed to compare the delivery of the antimicrobial gentamicin to the respiratory tract of adult horses following aerosol and intravenous administration. Nine adult horses were used in a crossover design. Aerosol administration of gentamicin was performed using a close fitting facemask and an ultrasonic nebulizer. Intravenous gentamicin was administered via a jugular venous catheter. Samples of pulmonary epithelial lining fluid were collected by bronchial lavage performed at 0.5, 4, 8 and 24 hours after gentamicin administration. All samples were analyzed for gentamicin concentration, and cytologic examination was performed on aliquots of bronchial lavage fluid from times 0.5, 8 and 24 hours. Comparisons were made using the Wilcoxon signed-rank test. The bronchial lavage fluid gentamicin concentration after aerosol administration was significantly greater (p<0.05) than after intravenous administration at 0.5, 4, and 8 hours. The bronchial lavage fluid total nucleated cell count increased significantly (p<0.05) from 0.5 to 24 hours following both routes of gentamicin administration, with the increase observed following aerosol administration being significantly greater (p<0.05) than that observed following intravenous administration. A significant increase in neutrophil count was detected between bronchial lavage fluid samples taken at 0.5 hours and 24 hours, regardless of route of gentamicin administration. We conclude that aerosol administration of gentamicin to the equine respiratory tract achieves bronchial lavage fluid gentamicin levels that are significantly higher than levels obtained following intravenous administration for at least the first 8 hours after administration, while inciting a mild inflammatory response. / Master of Science

Antimicrobial efficacy of recently approved lytic bacteriophage preparation Salmofresh™ against Salmonella was evaluated on chicken breast fillets as dip and surface application, which reduced Salmonella by 0.7-0.9 log CFU/g and 0.8-1 log CFU/g, respectively. Surface application of Salmofresh™ on Salmonella inoculated chicken breast followed by storage under modified atmosphere packaging (95% CO2/ 5% O2) reduced Salmonella by 1.2 log CFU/g. The combined application of Salmofresh™ with cetylpyridinium chloride (CPC) and lauric arginate (LAE) reduced Salmonella on chicken breast fillets by 1.2-1.4 log CFU/g and 0.9-1 log CFU/g, respectively. The sequential application of chemical antimicrobial (CPC, LAE, chlorine and peracetic acid) and Salmofresh™ in reducing Salmonella was tested in a chicken skin model. Dip treatment in peracetic acid (400ppm) followed by surface application of phage revealed the highest reduction of Salmonella up to 2.5 log CFU/cm2 on chicken skin.

An aerobic, Gram-negative, rod shaped and polarlagellated bacterium, designated strain MS586, was isolated from soybean rhizosphere in Mississippi. The taxonomic position of MS586 was determined using a polyphasic approach. Analysis of the housekeeping genes supported the novel position of MS586. The results were also supported by average nucleotide identity (ANI) values. Based on these data, it is proposed that strain MS586 represents a novel species, Pseudomonas mississippiensis, within the genus Pseudomonas. The type strain is MS586. Strain MS586 showed a broad-spectrum of antimicrobial activity against plant pathogenic bacteria and fungi that are economically important in agriculture. Preliminary studies using transposon-based mutagenesis showed that the gltB gene was associated with production of antifungal activity against the indicator fungus Geotrichum candidum. The research findings of strain MS586 have provided insights into its potential use as a biocontrol agent in plant disease management.

Paediatric community-acquired pneumonia (CAP) is common in North America. It is often treated with beta-lactam antimicrobials targeting S. pneumoniae, the most important cause of CAP in young children. Current guidelines recommend 10 days of therapy for paediatric CAP, regardless of severity; in contrast, mild CAP in adults is routinely treated with only 5 days of antimicrobials. There have been no definitive studies of 5-day vs. 10-day therapy for CAP in children. The objective of this thesis was to conduct a pilot RCT comparing 5 to 10 days of amoxicillin for the treatment of mild paediatric CAP and then design the multicentre follow-up trial. Children aged 6 months - 10 years with no significant past medical history presenting to the McMaster Children's Hospital emergency department with mild CAP were eligible for enrollment. All participants were randomized to either 10 days high-dose amoxicillin (90 mg/kg/day divided bid) or 5 days of high-dose amoxicillin + 5 days placebo. The primary outcome was clinical cure at day 14-18 post-enrollment. In total, 61 participants were recruited. The median participant age was 2.64 y. Only 60% of chest radiographs were reported by the radiologist as showing evidence of pneumonia. There were six treatment failures; one participant failed to defervesce on day 4, one participant had recurrent fevers leading to re-presentation to the emergency, and the other four participants did not meet clinical cure criteria but were essentially well at the time of follow-up. Study blinding has been maintained. The majority of previously healthy children with mild CAP who are well enough to be treated as outpatients appear to do well, regardless of duration of antimicrobial treatment. Feasibility and safety of the trial protocol have been demonstrated; the follow-up multicentre trial is slated to begin in mid-2015. / Thesis / Master of Science (MSc)