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Pathogenic characteristics of Pseudomonas aeruginosa bacteraemia isolates in a high-endemicity setting for ST175 and ST235 high-risk clones

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Abstract

Multidrug-resistant (MDR) Pseudomonas aeruginosa represents a major clinical concern. The interplay between antimicrobial resistance and virulence of P. aeruginosa was investigated in in vitro and in vivo studies. Thirty-eight well-characterized (21 MDR and 17 non-MDR) P. aeruginosa strains from patients with bacteraemia were analysed. Resistance phenotype, carbapenemase production, clonal relatedness, type III secretion system genotype, O-antigen serotype, cytotoxicity (ability to lyse cells) on A549 cells, and virulence (lethality in nematodes) in a Caenorhabditis elegans model were investigated. MDR strains showed lower cytotoxicity (35.4 ± 21.30% vs. 45.0 ± 18.78 %; P = 0.044) and virulence (66.7% vs. 100%; P = 0.011) than non-MDR strains. However, the pathogenicity of MDR high-risk clones varied broadly, with ST235 and ST175 clones being the most and least cytotoxic (51.8 ± 10.59% vs. 11.0 ± 1.25%; P < 0.0001) and virulent ([100% vs. 73.1; P = 0.075] and [0% vs. 93.9%; P < 0.0001], respectively). The pathogenicity of the ST235 clone was similar to that of non-MDR strains, and its ability to lyse cells and high virulence were related with the exoU-positive genotype. Furthermore, the O11 serotype was more frequent among the ST235 clone and exoU-positive genotype strains and was also essential for the pathogenicity of P. aeruginosa. Our data suggest that the pathogenicity of MDR high-risk clones is the result not only of the resistance phenotype but also of the virulence genotype. These findings have implications for the clinical management of patients and infection control programmes.

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Acknowledgements

We are thankful to María Dolores Folgueira and Fátima Lasala (Department of Clinical Microbiology, Hospital Universitario 12 de Octubre, Madrid, Spain) for their guidance on performing the cytotoxicity assay. We are also grateful to Janet Dawson for revising the English manuscript.

Funding

This work was supported by Plan Nacional de I+ D+ i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016) and cofinanced by European Development Regional Fund “A way to achieve Europe”. Esther Viedma was also supported by “Juan Rodés” fellowship grant (Instituto de Salud Carlos III). Raúl Recio received a SEIMC (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica) mobility fellowship to support his work in the microbiology laboratory (IdISBa).

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Authors and Affiliations

  1. Department of Clinical Microbiology, Instituto de Investigación Hospital 12 de Octubre (i + 12), Hospital Universitario 12 de Octubre, Madrid, Spain

    Raúl Recio, Esther Viedma, María Ángeles Meléndez-Carmona, Jennifer Villa, María Ángeles Orellana & Fernando Chaves

  2. Department of Clinical Microbiology, Instituto de Investigación Sanitaria Islas Baleares (IdISBa), Hospital Universitario Son Espases, Palma de Mallorca, Spain

    Irina Sánchez-Diener, Carlos Juan, Laura Zamorano & Antonio Oliver

  3. Department of Internal Medicine, Instituto de Investigación Hospital 12 de Octubre (i + 12), Hospital Universitario 12 de Octubre, Madrid, Spain

    Mikel Mancheño & Jaime Lora-Tamayo

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  1. Raúl Recio
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Correspondence to Raúl Recio.

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Ethical approval

This study was approved by the Research Ethics Committee of our centre (Health Research Institute, Hospital Universitario 12 de Octubre, Madrid, Spain) [ref. TP17/0041].

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Fig. S1.

A549 cytotoxicity results after 3 hours of infection (MOI = 100) of P. aeruginosa strains. PAO1 and PA14 strains are included for comparative purposes. Values are means ± SD for at least three wells from three independent plates (DOCX 33 kb)

Fig. S2.

A549 cytotoxicity results after 3 hours of infection (MOI = 100) of P. aeruginosa strains according to MLST genotype: ST235 (black tone), ST175 (grey tone) and other STs (white tone). PAO1 and PA14 strains are included for comparative purposes. Values are means ± SD for at least three wells from three independent plates (DOCX 56 kb)

Fig. S3.

A549 cytotoxicity results after 3 hours of infection (MOI = 100) of P. aeruginosa strains according to TTSS genotype: exoU+/exoS˗ (black tone), exoS+/exoU˗ (grey tone) and exoU˗/exoS˗ (white tone). PAO1 and PA14 strains are included for comparative purposes. Values are means ± SD for at least three wells from three independent plates (DOCX 56 kb)

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Recio, R., Sánchez-Diener, I., Viedma, E. et al. Pathogenic characteristics of Pseudomonas aeruginosa bacteraemia isolates in a high-endemicity setting for ST175 and ST235 high-risk clones. Eur J Clin Microbiol Infect Dis 39, 671–678 (2020). https://doi.org/10.1007/s10096-019-03780-z

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