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Biological markers of Pseudomonas aeruginosa epidemic high-risk clones
Xavier Mulet1, Gabriel Cabot, Alain A Ocampo-Sosa
1Servicio de Microbiología y Unidad de Investigación, Hospital Universitario Son Espases, Palma de Mallorca, Spain.
Abstract:
A limited number of Pseudomonas aeruginosa genotypes (mainly ST-111, ST-175, and ST-235), known as high-risk clones, are responsible for epidemics of nosocomial infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains worldwide. We explored the potential biological parameters that may explain the success of these clones. A total of 20 isolates from each of 4 resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS [susceptible to all antipseudomonals]), recovered from a multicenter study of P. aeruginosa bloodstream infections performed in 10 Spanish hospitals, were analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones (ST-175 [n = 6], ST-111 [n = 7], and ST-235 [n = 7]) recovered from different geographical locations was also studied. When unknown, genotypes were documented through multilocus sequence typing. The biological parameters evaluated included twitching, swimming, and swarming motility, biofilm formation, production of pyoverdine and pyocyanin, spontaneous mutant frequencies, and the in vitro competition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8 (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study belonged to high-risk clones. No significant differences were observed between clonally diverse ModR and MultiS isolates for any of the parameters. In contrast, MDR/XDR high-risk clones showed significantly increased biofilm formation and mutant frequencies but significantly reduced motility (twitching, swimming, and swarming), production of pyoverdine and pyocyanin, and fitness. The defined biological markers of high-risk clones, which resemble those resulting from adaptation to chronic infections, could be useful for the design of specific treatment and infection control strategies.
Insights
High-risk Pseudomonas aeruginosa clones, responsible for global nosocomial infections, exhibit enhanced biofilm formation and mutation rates but reduced motility and virulence factors. These traits aid in adaptation to chronic infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa, particularly high-risk clones like ST-111, ST-175, and ST-235, cause widespread nosocomial infections.
- Understanding the biological underpinnings of these successful clones is crucial for developing effective control strategies.
Purpose of the Study:
- To investigate the biological parameters differentiating high-risk MDR/XDR Pseudomonas aeruginosa clones from susceptible strains.
- To identify potential markers associated with the success and epidemic potential of specific P. aeruginosa genotypes.
Main Methods:
- Analysis of 20 isolates each from XDR, MDR, ModR, and MultiS resistance groups from a multicenter study in Spain.
- Genotyping using multilocus sequence typing (MLST) to identify high-risk clones.
- Evaluation of motility (twitching, swimming, swarming), biofilm formation, pyoverdine/pyocyanin production, mutant frequencies, and in vitro competition index (CI) using flow cytometry.
Main Results:
- High-risk clones predominated in XDR (100%), MDR (40%), and ModR (5%) bloodstream isolates.
- MDR/XDR high-risk clones demonstrated significantly increased biofilm formation and spontaneous mutant frequencies.
- Conversely, these clones exhibited significantly reduced motility, pyoverdine/pyocyanin production, and overall fitness compared to susceptible strains.
Conclusions:
- Specific biological markers, including enhanced biofilm formation and increased mutation rates, characterize successful high-risk Pseudomonas aeruginosa clones.
- These traits, resembling adaptations for chronic infections, offer potential targets for novel therapeutic and infection control interventions.
- Identifying these biological markers can aid in predicting and managing outbreaks of resistant P. aeruginosa infections.
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