Multidrug-resistant bacteria become a global threat. Antibiotics are thought to be powerful drugs against bacterial infections, however, their effectiveness has dramatically decreased due to antimicrobial resistance. Nowadays, not only many pathogens are resistant to multiple antibiotics but also a truly superbug which has no clinically-used drug to kill is found. Pseudomonas aeruginosa is current one of the most troublesome bacteria. This opportunistic pathogen is well-known for long-term colonization within the cystic fibrosis patients and possibly leads to serve infections. By the power of whole-genome sequencing technologies, recent reports show that P. aeruginosa can co-evolve within the host to adapt environmental changes and appears diverse phenotypes within the same specimen in the cystic fibrosis patients. Instead of cystic fibrosis, P. aeruginosa commonly causes nosocomial infections, especially in the lung. Repetitive infections by P. aeruginosa result in difficult treatment and poor outcome during hospitalization. We hypothesize that P. aeruginosa colonizes and co-evolves within hospitalized patients, as the same as cystic fibrosis ones. Here, we will investigate genetic and phenotypic changes of sequential isolates collected from the same individual with long-term hospitalization. In addition, we will also perform experimental evolutions in the laboratory to discover convergent mutations in response to antimicrobial resistance or host adaption. We will apply the whole-genome sequencing technologies together with bioinformatics analysis to reveal genetic alternations of clinical isolates from the same individual or laboratory evolved isolates. Meanwhile, we will characterize phenotypes associated virulence or antimicrobial resistance in either clinical or laboratory isolates. Patients with long-term hospitalization often experience treatment of antimicrobial agents or other drugs. Discovery of genetic alternations associated with antimicrobial resistance or host adaption may explain poor outcomes of patients after repetitive infections of P. aeruginosa in the molecular level. On the other hand, these findings may use to genetically subtype P. aeruginosa, and then to explore possible the high-risk lineage associated with poor patients in the future. Once the high-risk lineage is found, its genetic markers may be applied for diagnosis or monitor when patients long-term stay in the hospital.
|Effective start/end date||8/1/17 → 7/31/18|