< Back to previous page

Publication

Genomic insights into the emergence and spread of ‘high-risk’ **Klebsiella pneumoniae** and **Acinetobacter baumannii** clones

Book - Dissertation

While antibiotics still represent the major antibacterial agents for the treatment of bacterial infections, an increasing number of bacteria is becoming (multi-drug) resistant (MDR), complicating the treatment of infections. Carbapenems are highly effective antibiotics commonly used for the treatment of severe bacterial infections of MDR bacteria, which are resistant to first-line antibiotics. Of major concern, carbapenem resistance is on the rise, and in some countries it is so high that other drugs, usually reserved as last options, are widely used. As an example, colistin, an old drug that was essentially unused due to its toxicity, it’s now commonly adopted in some countries, and resistance toward this antibiotic is on the rise. Of the several pathogens associated with MDR, carbapenem-resistant K. pneumoniae and A. baumannii represent major concerns. Both pathogens frequently cause outbreaks of infections, while strains which are resistant to all available antibiotics are emerging. Concerning K. pneumoniae, a novel kind of superbug has been emerging recently. While MDR K. pneumoniae clones causing hospital outbreaks and hypervirulent, drug susceptible clones causing severe community-acquired infections were two separate concerns, strains that showed convergence of the two traits are emerging. Acquisition of hypervirulence and resistance genes have been observed in MDR and hypervirulent clones, respectively, especially in Asia. Tracking the emergence and evolution of such novel clones, which cause severe infections with limited treatment options, is fundamental. The decreasing cost of Whole Genome Sequencing (WGS) is allowing its increase implementation in bacterial diagnosis. However, there is still a lack of surveillance investigations for last-line resistance mechanisms and for convergence of resistance and hypervirulence traits. Moreover, while the phenotype prediction from the genomic data showed encouraging results, the understanding of the genetic resistance mechanisms of some drugs, such as colistin, is still limited, and novel in silico tools for the phenotype prediction are needed. We employed WGS and bioinformatics, together with phenotypic techniques, to address different problems: i) to decipher the colistin resistance mechanisms and the genomic epidemiology of clinical isolates of K. pneumonia and A. baumannii from countries where carbapenem resistance is sky-high, and colistin represent a life-saving agent. ii) to explore the longitudinal population dynamics of K. pneumonia in a major Chinese hospital, focusing on the simultaneous carriage of resistance and hypervirulence genes. iii) to predict the phenotype of K. pneumonia strains from their genomes. iv) to study a novel carbapenemase-encoding gene obtained from environmental bacteria.
Number of pages: 139
Publication year:2020
Keywords:Doctoral thesis
Accessibility:Open