Acinetobacter baumannii is an important nosocomial pathogen, frequently associated with morbidity and mortality in immunocompromised patients due to the immuno-ablative treatments, neutropenia and prolonged hospitalization. The ability of A. baumannii to survive in the healthcare setting makes it a frequent problematic pathogen in cancer centres. Much of the interest in A. baumannii has been attributed to its remarkable rapid acquisition of resistance mechanisms A. baumannii is an excellent example of genetic plasticity, with its ability to acquire and express resistance in plasmids and chromosome particularly to carbapenems The aim of this thesis is to look at the molecular epidemiology and resistance mechanisms of 34 non-duplicate A. baumannii in two cancer centres in Cairo, Egypt. Initial sequencing of the ubiquitous blaOXA-51-like gene revealed a large diversity within the strains, with eight different genes identified: blaOXA-64, blaOXA-65, blaOXA-66, blaOXA-69, blaOXA-71, blaOXA-78, blaOXA-94, blaOXA-89/100. Typing with Pulsed-field Gel Electrophoresis (PFGE) showed an overall similarity at only 28.69% between the isolates, with variation in pattern for isolates with similar blaOXA-51-like genes. Typing with Multilocus Sequence Typing (MLST) identified 6 new Sequence Types: ST408 - ST414, in addition to ST331 and ST108 which have been previously found in other regions of the world. All three OXA-type carbapenemases: blaOXA23, blaOXA40 and blaOXA58, responsible for conferring carbapenem resistance were found in the collection studied. Insertion sequences ISAba1, ISAba2 and ISAba3 have been found to upregulate the expression of blaOXA genes. ISAba1 was found upstream of blaOXA23 in 18 strains in this collection The first report of ISAba2 was identified upstream of a blaOXA-51-like gene in this collection. Additionally, ISAba3 was bracketing the blaOXA58 genes, and two isolates harboured hybrid promoters with IS1006 and IS1008 interrupting the upstream ISAba3 sequence. Resistance to Ceftazidime was mediated by Extended-spectrum β-lactamase (ESBL) genes belonging to PER-like group: blaPER-1, blaPER-7 and the first report of blaPER-3 gene and its genetic environment in A. baumannii. In conclusion, this study shows the diversity exhibited by A. baumannii in Egypt. The various resistance mechanisms illustrate the ability of A. baumannii in acquiring and expressing resistance genes, either on plasmids or in the chromosome. Furthermore, the results indicate an urgent need to strict infection control policies and surveillance of antimicrobial use in Egyptian hospitals.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:586439 |
| Date | January 2013 |
| Creators | Al-Hassan, Leena |
| Contributors | Hamouda, Ahmed; Doherty, Catherine; Amyes, Sebastian |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/8094 |
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