Thesis (M.S.)--Michigan State University. Dept. of Biochemistry and Molecular Biology, 2008. / Title from PDF t.p. (viewed on July 29, 2009) Includes bibliographical references (p. 78-81). Also issued in print.

Antibiotic resistance is increasing rapidly world wide. Resistance determinants have evolved long before antibiotics were used. Though horizontal gene transfer and mutation play a major role in the dissemination of antibiotic resistance genes their evolutionary origins remain obscure. A model system was used to investigate how they might arise in the first case. Plasmid borne erythromycin resistant clones were selected through marker rescue from genomic libraries of DNA from Gram positive organisms, maintained in E. coli. EryR determinants were recovered from nine libraries of 23 screened. Clone pMP1 (DNA from Mycobacterium parafortuitum) was the most resistant, with an MIC of 400 ìg/ml for erythromycin and 12 ìg/ml for azithromycin. Antibiotic resistance was not expressed in Rhodococcus erythropolis. Restriction maps were constructed for clones pMP1 and pMCX (DNA from Mycobacterium avium). Clone pMP1 was sub-cloned and the fragment carrying the EryR determinant (~2.4 kb) was sequenced. Analysis revealed 2 open reading frames (ORF1 and ORF2). ORF1 showed highest similarity to an FixB/FixA proteins and ORF2 showed similarity to a methyl transferase. Key words: antibiotic resistance,erythromycin, Gram positive DNA / Prof. E.R. Dabbs

Erythromycin is a macrolide antibiotic that inhibits not only mRNA translation but also 50S ribosomal subunit assembly in bacterial cells. An important mechanism of erythromycin resistance is the methylation of 23S rRNA by erm methyl transferase enzymes. A model for 50S ribosomal subunit formation suggests that the precursor particle which accumulates in erythromycin treated cells is the target for methyl transferase activity. Hybridization experiments identified the presence of 23S rRNA in the 50S precursor particle. The protein content of the 50S precursor particle was analyzed by MALDI-TOF mass spectrophotometry. These studies have identified 23 of 36 50S ribosomal proteins in the precursor. Methyltransferase assays demonstrated that the 50S precursor particle was a substrate for ermE methyltransferase. Competition experiments indicated that the enzyme could displace erythromycin from the 50S precursor particle and that the methyltransferase had a higher association constant for the precursor particle compared to that of erythromycin. Inhibition experiments showed that macrolide, lincosamide and streptogramin B compounds bound to the precursor particle with similar affinity and inhibited the ermE methyltransferase activity. These studies shed light on the interaction of ermE methyltransferase and erythromycin in this clinically important pathogen.

no / A total of 107 antibiotic-resistant propionibacteria were isolated from the face of 102 Egyptian acne patients, dermatology staff and controls. Erythromycin-clindamycin-resistant propionibacteria were chosen to detect erm(X) gene and it was detected in 29 of 107 (27%) strains. However, just 7 strains had IS1249I, 3 of them had also Tn5432. The erm(X) gene which is not carried on Tn5432 confers inducible resistance to telithromycin by erythromycin or clindamycin. The DNA sequences of the PCR amplification products of this new erm(X)-mediated antibiotic resistance showed >99% identity to the erm(X) gene isolated from a Corynebacterium jeikeium. Southern blotting analysis of the erm(X)-specific probe shows that there were two copies of this resistance gene integrated within the chromosomal DNA. This is the first report of erm(X) being carried by Propionibacterium acnes outside Europe. Whilst the gene is associated with Tn5432 in some strains, the data suggests other genetic element carrying erm(X). The high carriage of erm(X) may affect the efficacy of clindamycin and macrolides for acne treatment in Egypt. / Egyptian Ministry of Higher Education

Im Zusammenhang mit der Labmagenverlagerung zählen mangelnde Motilität und Entleerungsstörungen zu den häufigsten Problemen im postoperativen Zeitraum. In der vorliegenden Arbeit sollte geprüft werden, ob eine präoperative Erythromycingabe die Entleerung des Labmagens in den ersten 24 Stunden nach Reposition beeinflusst und so die klinische Rekonvaleszenz beschleunigt wird. Untersucht wurden 60 Milchkühe mit linksseitiger bzw.rechtsseitiger Labmagenverlagerung. Die abomasale Entleerungsrate der mit Erythromycin behandelten Tiere war signifikant höher als die der unbehandelten Tiere, sowohl in der Gruppe der linksseitig verlagerten als auch der rechtsseitig verlagerten Kühe.

Helicobacter pylori (hereinafter referred to as H. pylori) is a gram-negative bacteria which colonises the human stomach mucosa. Its role in the aethiopathogenesis of chronic gastritis, ulcer disorders of the gastroduodenum and MALT-lymphoma has been clearly demonstrated, and in connection with the occurrence of stomach cancer it has been indicated by the World Health Organisation (WHO) as a class I carcinogen. H. pylori infection can be detected from samples of stomach mucosa taken in an endoscopic examination (rapid urease test, microscopic examination, culture), or the non-invasive method can be used (13 C-Urea Breath Test or H. Pylori stool antigen test - HpSA). Effective therapy of H. pylori infection resides in the administration of a combination of antibiotics and a proton pump inhibitor. In recent years the resistance of bacterial strains to used antibiotics has been increasing on a worldwide scale, and we can also observe this trend in the case of H. pylori. If the level of resistance exceeds 20 % for clarithromycin and 40 % for metronidazole, these antibiotics are not recommended for the treatment of an infection caused by this bacteria. In a group of 61 patients at the Department of Internal Medicine at the University Hospital Motol who had undergone an endoscopic examination of the...

The fate and transformation of laboratory-prepared nano-ZnO, nano-Ag and nano-CeO2 in three aqueous solutions under different environmental conditions were investigated in this work. Over the past decades nanomaterials have been widely used in different technical fields and consumer goods. As a result, nanomaterials might enter the environmental media via different routes and then posed potential hazards to the environment and human health. Researches in this regard have received much attention worldwide. In this work it was found that the solubility of each nanomaterial was highly influenced by the solution pH, but not by the solution temperature. The maximal solubility for the tested nanomaterials was obtained at pH 3, namely about 100% for nano-ZnO and lower than 2% for both nano-Ag and nano-CeO2. The solution pH and ionic strength were found to affect the stability of nanoparticles in different aquatic environments. For the solution pH of higher than the isoelectric point of the concerned nanomaterial, the higher the solution pH is, the greater the degree of stabilization of nanoparticles would be. On the contrary, nanoparticles aggregated as the ionic strength of the solution exceeded its critical aggregation concentration (CAC). CAC for each concerned nanomaterial could also be graphically determined as the attachment efficiency (£\) of nanoparticles increased with increasing ionic strength of the solution and then leveled off after reaching CAC. Experimental results also showed that Zn(OH)2(s) would form when nano-ZnO was in the solution of pH 10. The crystalline structure of the said precipitates was confirmed by X-ray diffraction. Likewise, Ce4+ dissolved from nano-CeO2 reacted with SO42- in aqueous solution yielding Ce(SO4)2(s). Clearly, transformation of nanomaterials might take place when they are in contact with various species in different aquatic environments. Humic acid in aqueous solution was found to be beneficial to the stability of nanomaterial of concern. Efforts have also been made to study the reaction behaviors among di(2-ethylhexyl)phthalate, erythromycin, and selected nanomaterials when they co-existed in the same solution. Their interactions, however, seemed to be unobvious. In this work it was found that under sunlight irradiation nano-ZnO did show its antibiotic effect due to photocatalysis. Nano-Ag was proven to have a strong antibacterial ability even in natural aquatic environments. It yielded the total bacteria survival ratio of less than 2% within one hour of reaction. In summary, the findings of this study showed that the behaviors of nano-ZnO, nano-Ag, and nano-CeO2 in aqueous solutions could be greatly influenced by different factors in different reaction systems.

The Plasmodium falciparum parasite, carried by Anopheles mosquitoes, is currently a global problem due to the rising incidence of resistance of the parasite to available antimalaria drugs. Resistance and difficult treatment groups, including pregnant woman and young children, are pressing for the development of new, safe and effective prophylactic and treatment antimalarials. Because of the extensive process of developing new drugs, researchers and health care professionals have turned to combination therapy where a fast acting antimalarial is combined with slower acting drugs, such as antibiotics. The macrolide antibiotics, erytbromycin and azithromycin, have been studied to a limited extent for their potential antimalarial effect. Certain advantages, such as their safety profile (especially that of azithromycin) in pregnancy and administration to young children, motivates continual research into the advancement of the effect these drugs exude on malaria. Drug delivery systems contribute to the efficacy of medicines, conquering several difficulties of treatment with oral medication. Pheroid™ technology is a patented drug delivery system, mainly consisting of plant and essential fatty acids, and has been demonstrated to entrap, carry and deliver pharmacologically active compounds and other useful molecules. This study compared the in vitro effects of the macrolide antibiotics on the growth of a chloroquine-resistant strain (RSA 11) of Plasmodium falciparum to the effects of the macrolides entrapped in Pheroid™ vesicles on the same strain over and extended observation period of 144 hours. ELISA assays were conducted by analysing the HRP II (histidine-rich protein) levels on a pre-coated microtitre plate. The effects of the type of formulation, concentration and time were compared. The in vitro difference between erythromycin alone and entrapped in Pheroid™ vesicles were found to be statistically significant (p = 0.000000) while the effects of both formulations did not seem to be concentration dependant (p = 0.628424). Prolonged exposure was also statistically meaningful (p = 0.008268), though it seems that exposure need not exceed 96 hours. The type of formulation, in the case of azithromycin (azithromycin alone vs. azitbromycin entrapped in Pheroid™ vesicles), proved statistically significant (P = 0.002572), while neither formulation seemed concentration dependant (P = 0.427731). Prolonged exposure was found to be statistically insignificant for azithromycin (P = 0.221941). / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

The Plasmodium falciparum parasite, carried by Anopheles mosquitoes, is currently a global problem due to the rising incidence of resistance of the parasite to available antimalaria drugs. Resistance and difficult treatment groups, including pregnant woman and young children, are pressing for the development of new, safe and effective prophylactic and treatment antimalarials. Because of the extensive process of developing new drugs, researchers and health care professionals have turned to combination therapy where a fast acting antimalarial is combined with slower acting drugs, such as antibiotics. The macrolide antibiotics, erytbromycin and azithromycin, have been studied to a limited extent for their potential antimalarial effect. Certain advantages, such as their safety profile (especially that of azithromycin) in pregnancy and administration to young children, motivates continual research into the advancement of the effect these drugs exude on malaria. Drug delivery systems contribute to the efficacy of medicines, conquering several difficulties of treatment with oral medication. Pheroid™ technology is a patented drug delivery system, mainly consisting of plant and essential fatty acids, and has been demonstrated to entrap, carry and deliver pharmacologically active compounds and other useful molecules. This study compared the in vitro effects of the macrolide antibiotics on the growth of a chloroquine-resistant strain (RSA 11) of Plasmodium falciparum to the effects of the macrolides entrapped in Pheroid™ vesicles on the same strain over and extended observation period of 144 hours. ELISA assays were conducted by analysing the HRP II (histidine-rich protein) levels on a pre-coated microtitre plate. The effects of the type of formulation, concentration and time were compared. The in vitro difference between erythromycin alone and entrapped in Pheroid™ vesicles were found to be statistically significant (p = 0.000000) while the effects of both formulations did not seem to be concentration dependant (p = 0.628424). Prolonged exposure was also statistically meaningful (p = 0.008268), though it seems that exposure need not exceed 96 hours. The type of formulation, in the case of azithromycin (azithromycin alone vs. azitbromycin entrapped in Pheroid™ vesicles), proved statistically significant (P = 0.002572), while neither formulation seemed concentration dependant (P = 0.427731). Prolonged exposure was found to be statistically insignificant for azithromycin (P = 0.221941). / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2010.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2002. / Härtill 5 uppsatser.