New Sequence Type ST3449 in Multidrug-Resistant Pseudomonas aeruginosa Isolates from a Cystic Fibrosis Patient
Catalina Díaz-Ríos1, Marta Hernández2, David Abad2
1Instituto de Investigación Sanitaria Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain.
Abstract:
Pseudomonas aeruginosa is one of the most critical bacterial pathogens associated with chronic infections in cystic fibrosis patients. Here we show the phenotypic and genotypic characterization of five consecutive multidrug-resistant isolates of P. aeruginosa collected during a month from a CF patient with end-stage lung disease and fatal outcome. The isolates exhibited distinct colony morphologies and pigmentation and differences in their capacity to produce biofilm and virulence potential evaluated in larvae of Galleria mellonella. Whole genome-sequencing showed that isolates belonged to a novel sequence type ST3449 and serotype O6. Analysis of their resistome demonstrated the presence of genes blaOXA-396, blaPAO, aph(3')-IIb, catB, crpP and fosA and new mutations in chromosomal genes conferring resistance to different antipseudomonal antibiotics. Genes exoS, exoT, exoY, toxA, lasI, rhlI and tse1 were among the 220 virulence genes detected. The different phenotypic and genotypic features found reveal the adaptation of clone ST3449 to the CF lung environment by a number of mutations affecting genes related with biofilm formation, quorum sensing and antimicrobial resistance. Most of these mutations are commonly found in CF isolates, which may give us important clues for future development of new drug targets to combat P. aeruginosa chronic infections.
Insights
This study characterizes multidrug-resistant Pseudomonas aeruginosa isolates from a cystic fibrosis patient, revealing genetic adaptations for survival in the lung. These findings offer insights for developing new therapeutic targets against chronic P. aeruginosa infections.
Area of Science:
- Medical Microbiology
- Genomics
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is a critical pathogen in cystic fibrosis (CF) chronic infections.
- Multidrug-resistant (MDR) P. aeruginosa poses a significant threat to CF patients.
Purpose of the Study:
- To perform phenotypic and genotypic characterization of consecutive MDR P. aeruginosa isolates from a fatal CF case.
- To identify genetic adaptations and virulence factors contributing to P. aeruginosa persistence in the CF lung.
Main Methods:
- Phenotypic analysis including colony morphology, pigmentation, biofilm formation, and virulence assays in Galleria mellonella.
- Whole genome sequencing to determine sequence type, serotype, and identify resistance and virulence genes.
- Analysis of mutations in chromosomal genes related to antibiotic resistance.
Main Results:
- Five MDR P. aeruginosa isolates belonged to a novel sequence type ST3449 and serotype O6.
- Isolates displayed distinct phenotypic traits and carried specific resistance genes (e.g., blaOXA-396, aph(3')-IIb) and virulence genes (e.g., exoS, toxA).
- Identified mutations in chromosomal genes and genes related to biofilm formation and quorum sensing indicate adaptation to the CF lung environment.
Conclusions:
- Clone ST3449 demonstrates significant adaptation to the CF lung through mutations affecting biofilm, quorum sensing, and antimicrobial resistance.
- These adaptive mutations are common in CF isolates, providing potential targets for novel therapies.
- Understanding these adaptations is crucial for combating chronic P. aeruginosa infections in cystic fibrosis.
