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The design and synthesis of antibacterial inhibitors of NAD synthetaseMoro, Whitney Beysselance. January 2007 (has links) (PDF)
Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed Feb. 4, 2010). Additional advisors: Subramaniam Ananthan, David E. Graves, Craig D. Smith, Sadanandan E. Velu. Includes bibliographical references.
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Quinolone trafficking via outer membrane vesicles in Pseudomonas aeruginosaWarren, Lauren Mashburn, 1981- 25 September 2012 (has links)
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen often infecting the lungs of individuals with the heritable genetic disease cystic fibrosis and the peritoneum of those undergoing continuous peritoneal dialysis. Often these infections are not caused by colonization with P. aeruginosa alone but instead by a consortium of pathogenic bacteria. Little is known about growth and persistence of P. aeruginosa in vivo, and less is known about the impact of coinfecting bacteria on P. aeruginosa pathogenesis and physiology. In this dissertation I used a rat dialysis membrane peritoneal model to evaluate the in vivo transcriptome of P. aeruginosa in monoculture and in coculture with Staphylococcus aureus. Monoculture results indicate that approximately 5% of all P. aeruginosa genes are differentially regulated during growth in vivo. Included in this analysis are genes important for iron acquisition and growth in lowoxygen environments. The presence of S. aureus caused decreased transcription of P. aeruginosa iron-regulated genes during in vivo coculture, indicating that the presence of S. aureus increases usable iron for P. aeruginosa in the environment. This lysis was shown to be dependent on antimicrobial quinolones produced by P. aeruginosa. I demonstrate that these quinolones are present in outer membrane vesicles (MVs). Not only were these quinolones present in MVs, but the quorum sensing molecule; 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas Quinolone Signal; PQS) was also packaged into MVs and was necessary for MV formation. These findings illustrate that a prokaryote possesses a signal trafficking system with features common to those used by higher organisms and outlines a novel mechanism for delivery of a signal critical for coordinating group behaviors in P. aeruginosa. Although MVs are involved in important processes besides signaling, the molecular mechanism is unknown. To provide insight into the molecular mechanism of MV formation, I examined the interaction of PQS with bacterial lipids. In this work, I demonstrated that PQS interacts strongly with the acyl chains and 4’-phosphate of bacterial lipopolysaccharide. The results of my studies provide molecular insight into P. aeruginosa MV formation and demonstrate that quorum signals serve important non-signaling functions. Finally, I propose a model of PQSmediated MV formation where PQS interacts with specific outer membrane components to allow the necessary curvature for MV formation. / text
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Molecular characterization of fluoroquinolone resistance in mycobacterium tuberculosisLau, Wing-tong, Ricky., 劉永棠. January 2011 (has links)
The global emergence of drug resistance is posing increasing difficulties in
the public health control and treatment of tuberculosis (TB). Fluoroquinolones (FQs)
are regarded as having a pivotal role among the antimicrobial agents in multidrug
regimens against multidrug-resistant tuberculosis (MDR-TB). Thus, early diagnosis
of fluoroquinolone-resistant (FQr) MDR-TB and extensively drug-resistant
tuberculosis (XDR-TB) by molecular tests has predictive value for the guidance of
TB therapy.
The pharmacokinetic (PK) and pharmacodynamic (PD) indices are valuable
parameters to evaluate the activity and efficacy of fluoroquinolones (FQs) based upon
the bactericidal effect and prevention of the emergence of resistance. In the first part
of this study, the potencies of ofloxacin (OFX) and moxifloxacin (MXF) against
clinical isolates of MDR-TB in terms of their PK/PD indices (Cmax/MIC90,
AUC/MIC90, Cmax/MPC90 and AUC/MPC90) were investigated and compared. The
results revealed that MXF displays higher ratios of PK/PD in vitro and could serve as
a promising agent for the treatment of MDR-TB.
Molecular tests on resistance genes are reliable and rapid technology for
diagnosis of drug-resistant TB which facilitates timely patient management and
public health control of TB. In the second part of the study, the feasibility of a PCRsequencing
assay for the examination of mutations in the quinolone-resistance-determining-
region (QRDR) of the gyrase A (gyrA) gene in FQ-resistant (FQr)
Mycobacterium tuberculosis in direct clinical specimens was evaluated. As
determined by gyrA QRDR DNA sequencing analysis, complete concordance of
phenotypic and genotypic outcomes was demonstrated. The results indicate that the
molecular assay is an accurate and effective method for the diagnosis of FQr TB and
allows identification of mixed resistant variants in the same patient. GyrA mutations
that associated with FQr in clinical isolates of M. tuberculosis were clustered in
hotspot codons 88, 90, 91 and 94, corroborating other reports. We also detected a
novel gyrA Ala74Ser mutation in M. tuberculosis directly from the respiratory
specimens by using the PCR-DNA sequencing assay.
In the third part of this study, the functional effect of the Ala74Ser mutant was
verified through study of the DNA supercoiling inhibitory activities of OFX and
MXF against the recombinant DNA gyrase. Fifty percent inhibitory concentrations
(IC50) of FQs against the DNA supercoiling activities of the recombinant DNA gyrase
complex reconstituted with gyrA Ala74Ser were eight-fold and 14-fold greater than
the wild-type H37Rv reference strain, and results correlated well with their
phenotypic drug susceptibilities. Besides, a combination of gyrA mutations
(Glu21Gln, Ser95Thr and Gly668Asp) was also characterized to be non-functional
polymorphisms. The impact of the gyrA Ala74Ser mutation on drug binding affinity
was elucidated through a crystal structure model of the gyrA-MXF-DNA cleavage
complex. Alanine at position 74 of gyrA in M. tuberculosis, which corresponds to the
alanine at position 67 of gyrA in Escherichia coli, is an amino acid lying in the α3
helix domain which forms a hydrophobic interface between the gyrA-gyrA dimer.
Perturbation of the gyrA-gyrA dimer interface caused by the Ala74Ser mutation
probably disturbs the putative drug binding pocket, and leads to the reduction of the
binding affinity of FQ due to the distance effect. This is the first report verifying that
gyrA Ala74Ser mutation alone is responsible for FQr in M. tuberculosis. / published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy
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A search for antibacterial substances from certain plants collected in southern ArizonaAtterbury, Joan, 1920- January 1949 (has links)
No description available.
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The effect of doping titanium dioxide nanoparticles on phase transformation, photocatalytic activity and anti-bacterial propertiesBuzby, Scott Edward. January 2008 (has links)
Thesis (Ph.D.)--University of Delaware, 2007. / Principal faculty advisor: S. Ismat Shah, Dept. of Materials Science . Includes bibliographical references.
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Characterisation of antibiotic-resistant Propionibacterium acnes from acne vulgaris and other diseases /Oprica, Cristina, January 2006 (has links)
Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.
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Synthesis and applications of novel antimicrobial polymeric materialsLee, Jaewoong, Broughton, Royall M. January 2006 (has links) (PDF)
Dissertation (Ph.D.)--Auburn University, 2006. / Abstract. Vita. Includes bibliographic references.
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Quinolone trafficking via outer membrane vesicles in Pseudomonas aeruginosaWarren, Lauren Mashburn, January 1900 (has links)
Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.
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Effects of fluoroquinolones on the immune systemRiesbeck, Kristian. January 1994 (has links)
Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.
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Antibacterial activity of some marine planktonic algae in Hong Kong /Lo, Shiu-hong. January 1996 (has links)
Thesis (M. Phil.)--University of Hong Kong, 1996. / Includes bibliographical references (leaf 84-93).
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