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Comparative phenotypic and genotypic analysis of distinct Pseudomonas aeruginosa T3SS effector genotypes
Nada K Alharbi1, Naser A El-Sawy2, Naief A Dahran3
1Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Background:
Pseudomonas aeruginosa (P. aeruginosa) causes healthcare- and community-associated infections with high antimicrobial resistance and virulence diversity. The type III secretion system (T3SS) effectors genotypes (exoS+, exoU+, exoT+, and exoY+) play central roles in pathogenesis, yet their relationships with antimicrobial resistance, virulence profiles, serotypes, and clinical manifestations remain incompletely defined.
Methods:
Five hundred clinical specimens, sputum, urine, burn, wound, and eye exudates, 100 each, were collected from multiple hospitals for isolation of P. aeruginosa. Phenotypic and genotypic methods identified isolates and characterized T3SS effector genotypes, antimicrobial susceptibility, resistance genes, virulence genes, and serotypes. Clustering, strain typing, and correlation analyses assessed associations among resistance, virulence, epidemiology, and disease severity.
Results:
Among 125 isolates, exoS+ was the most prevalent T3SS effector, followed by exoU+, while exoT+ and exoY+ were less frequent. The exoU+ isolates were consistently associated with severe clinical manifestations across specimen types and were more often hospital acquired, with enrichment for serotypes O6 and O11. The exoS+ isolates showed broader serotype diversity with balanced hospital and community acquisition, whereas ExoT and ExoY were mainly associated with O6 and O11, with ExoY more common in community-acquired cases but less prevalent overall. Despite widespread antimicrobial resistance and broad distribution of resistance genes, polymyxin remained the most effective agent, with a low resistance rate of 15.2%. Multidrug resistance affected 81.6% of isolates and was observed across all T3SS effector genotypes, with frequent coexistence of resistance and virulence genes within individual isolates. Hierarchical clustering revealed marked intra-group and inter-group heterogeneity, with no evidence of dominant clonal expansion by effector genotype or specimen type, and correlation analysis showed weak associations among resistance, virulence, serotypes, and epidemiological features, except for a consistent link between exoU+ and markers of severe tissue injury.
Conclusions:
P. aeruginosa isolates form a heterogeneous, non-clonal population with independent resistance and virulence traits, while T3SS effector genotypes, especially exoU+, best predicts disease severity. The data suggest that pathogenicity in P. aeruginosa is driven by independently assorting resistance and virulence traits, not by fixed clonal backgrounds. These findings support integrating T3SS effector profiling into clinical risk assessment and surveillance.
Insights
Pseudomonas aeruginosa infections are diverse, with type III secretion system (T3SS) effector genotypes like exoU+ predicting severe disease. Resistance is common, but polymyxin remains effective, highlighting T3SS profiling for risk assessment.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Pseudomonas aeruginosa causes diverse infections with significant antimicrobial resistance.
- Type III secretion system (T3SS) effectors are key virulence factors, but their associations with resistance and clinical outcomes are unclear.
Purpose of the Study:
- To investigate the relationships between T3SS effector genotypes, antimicrobial resistance, virulence factors, serotypes, and clinical manifestations of P. aeruginosa infections.
- To assess the population structure and identify predictors of disease severity in P. aeruginosa.
Main Methods:
- Collected 500 clinical isolates of P. aeruginosa from various specimen types.
- Characterized isolates for T3SS effector genotypes (exoS, exoU, exoT, exoY), antimicrobial susceptibility, resistance and virulence genes, and serotypes.
- Utilized clustering and correlation analyses to assess associations between resistance, virulence, epidemiology, and disease severity.
Main Results:
- ExoS+ was the most prevalent T3SS effector genotype; exoU+ isolates were linked to severe disease and hospital acquisition.
- Antimicrobial resistance was widespread, with polymyxin being the most effective agent.
- Isolates showed heterogeneity, with weak associations between resistance, virulence, serotypes, and epidemiology, except for exoU+ and severe tissue injury.
Conclusions:
- P. aeruginosa populations are heterogeneous, with independent resistance and virulence traits.
- T3SS effector genotypes, particularly exoU+, are strong predictors of disease severity.
- Integrating T3SS effector profiling into clinical risk assessment and surveillance is recommended.
