Browsing by Subject "E coli"

Constantly increasing level of bacteria becoming resistant to clinically relevant antibiotics challenges the modern medical achievements made over the past century. In global scale, one of the most significant information gaps concerning the occurrence of resistant bacteria is located in West African countries. Klebsiella pneumoniae and Escherichia coli strains resistant to 3rd generation cephalosporins and carbapenems are a major risk to public health through infections with limited or no available treatment options. The resistance to these antibiotics among Enterobacteriaceae is mainly mediated by hydrolyzing enzymes such as extended-spectrum beta-lactamases (ESBL). The focus of this thesis is to study the genes encoding these enzymes and other resistance factors found in K. pneumoniae and E. coli isolated from human stool and waste water samples in Burkina Faso and Mali. Tree Enterobacteriaceae isolates were selected for whole genome sequence (WGS) analysis based on their phenotypic resistance profiles defined by disk diffusion method. Reads were assembled to draft genomes and the genomes were studied for their antibiotic resistance genes, virulence genes and their associations to mobile genetic elements found in these isolates’ genomes. Additionally a pan-genome was created to investigate species specific features of K. pneumoniae and their role in heavy load of antibiotic resistance genes among these isolates. Pan-genome consisted of two genomes sequenced in this study and 12 genomes from the publically available database. 16-month old Burkinabe child was a carrier of one ESBL-producing K. pneumoniae (isolate Burkina_1) and one ESBL-positive E. coli along with the resistance to multiple other antibiotics. With genome wide analysis the K. pneumoniae strain could be described as sequence type (ST) 45 representing, multidrug resistant and ESBL-gene CTX-M-15 carrying strain with highly similar virulence gene profile to strains previously described as pathogenic K. pneumoniae causing neonatal sepsis. K. pneumoniae isolated from the stool sample of an adult living in Burkina Faso was found to be multidrug resistant, though non-ESBL-producer strain (isolate Burkina_2). The isolate showed no similarity to any previously described sequence type. CTX-M-15 encoding E. coli of ST38 (isolate Mali_1) carried by Malian child showed resistance to five different classes of antibiotics in addition to the 3rd generation cephalosporins. At the same time the isolate showed hybrid virulence gene profile with virulence genes associated to many different E. coli pathotypes including neonatal meningitis causing E. coli (NMEC). The exceptional plasticity of K. pneumoniae genome could be recognized as one of the putative explanations for the high number of resistance genes found among the isolates studied in this work. Antibiotic resistance genes were found to be associated to mobile genetic elements (MGE) and as the genetic plasticity is caused by the acquisition of external genetic material via MGEs such as plasmids, this can lead to indirect accumulation of resistance genes in these genomes. The results in this thesis work show alarming examples of pathogens that potentially cause severe infections, have extremely narrow or no treatment options and are carried by infants. These findings are in line with the few data about the level of faecal carriage of ESBL-producing strains by people in Burkina Faso and Mali reported previously.