Antimicrobial Resistance and Comparative Genome Analysis of Klebsiella pneumoniae Strains Isolated in Egypt

Abstract

Klebsiella pneumoniae is an important human pathogen in both developing and industrialised countries that can causes a variety of human infections, such as pneumonia, urinary tract infections and bacteremia. Like many Gram-negative bacteria, it is becoming resistant to many frontline antibiotics, such as carbapenem and cephalosporin antibiotics. In Egypt, K. pneumoniae is increasingly recognised as an emerging pathogen, with high levels of antibiotic resistance. However, few Egyptian K. pneumoniae strains have been sequenced and characterised. Hence, here, we present the genome sequence of a multidrug resistant K. pneumoniae strain, KPE16, which was isolated from a child in Assiut, Egypt. We report that it carries multiple antimicrobial resistance genes, including a bla_NDM-1 carbapenemase and extended spectrum β-lactamase genes (i.e., bla_SHV-40, bla_TEM-1B, bla_OXA-9 and bla_CTX-M-15). By comparing this strain with other Egyptian isolates, we identified common plasmids, resistance genes and virulence determinants. Our analysis suggests that some of the resistance plasmids that we have identified are circulating in K. pneumoniae strains in Egypt, and are likely a source of antibiotic resistance throughout the world.

Keywords: Klebsiella pneumoniae; antibiotic resistance; virulence; whole genome sequencing.

Figure 1

Comparison of the K. pneumoniae MGH 78578 chromosome with the draft genomes of K. pneumoniae strains KPE16, SF, SK, HM, and SP. The figure shows the comparison of the K. pneumoniae MGH 78578 chromosome with the genomes of K. pneumoniae strains KPE16, SF, SK, HM, and SP using GCview [32]. The outer two rings display the genes (CDS) and features of the K. pneumoniae MGH 78578 chromosome (CP000647.1) on both strands, with selected features labelled [30]. The blue, green, gold, red, and pink rings illustrate the BLAST results when the genome sequences of KPE16, SF, SK, HM, and SP, respectively, are compared to the MGH 78578 chromosome, with shaded regions indicating homology. The inner ring displays the GC content (black) for the K. pneumoniae MGH 78578 chromosome.

Figure 2

Analysis of plasmids carried by K. pneumoniae strain KPE16. The figure shows the comparison of the K. pneumoniae plasmids (A) p2 (CP009115.1) [14] and (B) pKP1–19 (CP012884.1) [44] with the genomes of K. pneumoniae strains KPE16, SF, SK, HM, and SP using GCview [32]. In both panels, the outer two rings display the genes (CDS) of each plasmid on both strands, with plasmid replicons and selected features labelled. The blue, green, gold, red, and pink shading illustrates the BLAST results when the genome sequences of KPE16, SF, SK, HM, and SP, respectively, are compared with each plasmid. Shaded regions indicate homology.

Figure 3

Analysis of plasmids carried by K. pneumoniae strains SF, SK, and HM. The figure shows the comparison of (A) Salmonella enterica subsp. enterica serovar Heidelberg plasmid pSH111_166 (JN983043.1) [46], (B) K. pneumoniae plasmid pKpn14-4 (CP047704.1) [15] and (C) K. pneumoniae MGH 78578 plasmid pKPN4 (CP000649.1) [30] with the genomes of K. pneumoniae strains SF, SK, HM, SP and KPE16, using GCview [32]. In all panels, the outer two rings display the genes (CDS) of each plasmid on both strands, with plasmid replicons labelled. In panels (A,B) the blue, green, gold, red, and pink shading illustrates the BLAST results when the genome sequences of SF, SK, HM, SP, and KPE16, respectively, are compared with each plasmid. In panel (C), the light blue, green, gold, and dark blue shading illustrates the BLAST results when the genome sequences of SF, SK, HM and the contigs that are specific to SK/HM only (after genome subtraction) are compared to pKPN4. Shaded regions indicate homology.

Figure 4

Analysis of the IncFIB(K) replicon carried by K. pneumoniae strain SP. The figure shows the comparison of K. pneumonia plasmid pTHO-004-1 (AP022528.1) with the genomes of K. pneumoniae strains SP, SF, SK, and HM, using GCview [32]. The outer two rings display the genes (CDS) on both strands, with the IncFIB(K) plasmid replicon and selected features labelled. The blue, green, gold, and red shading illustrates the BLAST results when the genome sequences of SP, SF, SK, and HM, respectively, are compared with pTHO-004-1. Shaded regions indicate homology.