Please use this identifier to cite or link to this item: http://ir.library.ui.edu.ng:8080/jspui/handle/123456789/592
Title: MOLECULAR BASIS OF MULTIDRUG RESISTANCE IN UROPATHOGENIC KLEBSIELLA PNEUMONIAE FROM SOUTHWESTERN NIGERIA
Other Titles: A THESIS IN THE DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY, SUBMITTED TO THE FACULTY OF PHARMACY IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY OF THE UNIVERSITY OF IBADAN
Authors: Soge, O. O.
Keywords: Klebsiella pneumoniae
Mobile genetic elements
Extended-spectrum beta lactamases (ESBLs)
Issue Date: Feb-2007
Abstract: There is paucity of information on the molecular mechanisms of bacterial antibiotic resistance in many parts of Africa, including Nigeria. This study was undertaken to determine the prevalence of uropathogenic Klebsiella pneumoniae as a causative agent of human urinary tract infections (UTI) in Southwestern Nigeria; genetically characterize the multiple antibiotic resistance determinants and describe the genetic locations of the resistance genes. Antimicrobial susceptibilities were performed on 96 K. pneumoniae clinical isolates using the antibiotic disk diffusion method. The MICs were initially determined by VITEK automated system and confirmed by the agar dilution method. A total of 30 antimicrobial agents belonging to the β-Iactams, fluoroquinolones, tetracyclines, chloramphenicol, florfenicol, aminoglycosides and macrolides were tested. Plasmid DNA was isolated by the alkaline lysis method. The ESBLs were phenotypically characterized by isoelectric focusing and the genetic characterization of the resistance genes achieved by polymerase chain reaction, DNA-DNA hybridization, cloning, transformation and sequencing. The incidence of K. pneumoniae among cases of UTI studied was observed to be 27%. All the K. pneumoniae isolates investigated (n=96) were found to be resistant to ampicillin and had resistance rates of >90% to tetracycline, colistin, streptomycin, amoxicillinlclavulanic acid, and chloramphenicol. All the isolates were resistant to three or more antibiotics. All 65 randomly sampled isolates were found to carry 1 - 8 plasmids ranging in size between <2.27 and 320 kb. Fifty-seven percent of the isolates carried blaCTX-M-1 genes that were associated with large plasmids (58 - 320 kb) which also carried the following genes: tet(A), aadA2, aac(3)-II and aac (6')-Ib, mph(A) and erm(B), blaTEM-1, qnrBl, sul1 and sul2, dfr, and intl. Seventy-seven percent of the isolates produced TEM β-Iactamases, 90% produced SHV , β-Iactamases and 13% produced AmpC β-Iactamases. The other resistance genes identified in varying proportions were tet(A), tet(B), tet(C) and tet(D) which were located on plasmids; tet(M/O/S) found on the chromosome; the MLS genes erm(B), mef(A), ere(B), mph(A), mph(B), and mph(D) which were either plasmid-borne or chromosomal; and the catB4/catB8, catA1, catA2, catA3 and florR genes which were all located on plasmids. This is the first full characterization of CTX-M-15 in West Africa, It is also the first report of catA2, catA3 and multiple cat genes in the genus Klebsiella. This study also describes for the first time, the association of the blacrxss plasmids with rRNA methylase erm(B), and phosphorylase mph(A) both coding for macrolide resistance; catA2, catA3 and floR for chloramphenicol!florfenicol resistance. This is also the first description in an African bacterial isolate of plasmid-mediated resistance gene qnrBJ; and the aac (6')-Ib-cr variant which concurrently methylates both the aminoglycosides and the fluoroquinolones. A novel linkage between the conjugative transposon Tn916 and the Gram-positive mercury (mer) operon was also described.
URI: http://hdl.handle.net/123456789/592
Appears in Collections:Academic Publications in Pharmaceutical Microbiology

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