Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.584859
Title: Role of ureaplasma spp in neonatal lung disease, activation of the complement system and molecular mechanisms of antibiotic resistance
Author: Beeton, Michael L.
Awarding Body: Cardiff University
Current Institution: Cardiff University
Date of Award: 2010
Availability of Full Text:
Access through EThOS:
Access through Institution:
Abstract:
Ureaplasmas are some of the smallest and simplest free-living organisms known. Little is understood regarding the effects of the complement system upon clearance of these pathogens, but when the immune system fails to control Ureaplasma colonization disease, such as chronic lung disease of prematurity (CLD), can occur. Treatment of such Ureaplasma infections, especially in neonates, is limited by pathogen and host factors. Treatment can be further compromised by antibiotic resistance. Firstly this thesis examines an in vitro system for determining the bactericidal capacity of a selection of human sera against four representative serovars of Ureaplasma parvum. Results showed that the classical activation pathway was essential for the killing of all U. parvum serovars, with little effect being attributed to the alternative or lectin pathways. Additionally serovar 3 was shown to be the most serum sensitive isolate. Secondly the association between presence of Ureaplasma and 16S rRNA with development of CLD was examined in a prospective cohort of 192 neonates. Data suggested that presence of Ureaplasma as well as 16S rRNA was significantly associated with development of CLD as well as increased levels of inflammatory mediators IL-6 and IL-8. Finally a retrospective cohort of 61 Ureaplasma isolates was examined for resistance to various antibiotics. High level macrolide resistance in isolate UHWO10 resulted from a two amino acid deletion within the L4 ribosomal protein (R66Q67). Tetracycline resistance in isolate HPA23 resulted from the presence of the tetM gene while a ciprofloxacin resistance in isolate HPA18 resulted from a D82N substitution within the ParC protein. No differences were found in the GyrA, GyrB or ParE proteins. Comparison of type II topoisomerase genes from all Ureaplasma serovars revealed that mutations previously associated with resistance where wrongly identified and were a result of species or serovar specific polymorphisms.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.584859  DOI: Not available
Share: