Variation in the response to antibiotics and life-history across the major Pseudomonas aeruginosa clone type (mPact) panel

Tueffers, L.; Batra, A.; Zimmermann, J.; Botelho, J.; Buchholz, F.; Liao, J.; Mendoza Mejia, N.; Munder, A.; Klockgether, J.; Tuemmler, B.; Rupp, J.; Schulenburg, H.

doi:10.1101/2024.01.15.575732

bioRxiv · 10.1101/2024.01.15.575732

Variation in the response to antibiotics and life-history across the major Pseudomonas aeruginosa clone type (mPact) panel

Tueffers, L.·Batra, A.·Zimmermann, J.·Botelho, J.·Buchholz, F.·Liao, J.·Mendoza Mejia, N.·Munder, A.·Klockgether, J.·Tuemmler, B.·Rupp, J.·Schulenburg, H.

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Abstract

Pseudomonas aeruginosa is a ubiquitous, opportunistic human pathogen. Since it often expresses multidrug resistance, it is ranked by the World Health Organization among the top 3 high priority pathogens, for which new treatment options are urgently required. An evaluation of new treatments is usually performed experimentally with one of the canonical laboratory strains (e.g., PAO1 or PA14). However, these two strains are unlikely representative of the strains infecting patients, because they have adapted to laboratory conditions and do not capture the enormous genomic diversity of the species. Here, we characterized the major P. aeruginosa clone type (mPact) panel. This panel consists of 20 strains, which reflect the genomic diversity of the species, cover all major clone types, and have both patient and environmental origins. We found significant strain variation in distinct responses towards antibiotics and general growth characteristics. Only few of the measured traits are related, and if so, only for specific antibiotics. Moreover, high levels of resistance were only identified for clinical mPact isolates and could be linked to known AMR (antimicrobial resistance) genes in the sequenced genomes. One strain also produced highly unstable AMR, indicating an evolutionary cost to resistance expression. By linking isolation source, growth, and virulence to life history traits, we further identified specific adaptive strategies for individual mPact strains towards either host processes or degradation pathways. Overall, the mPact panel provides a reasonably sized set of distinct strains, enabling in-depth analysis of new treatment designs or evolutionary dynamics in consideration of the species genomic diversity. ImportanceNew treatment strategies are urgently needed for high risk pathogens such as the opportunistic and often multidrug resistant pathogen Pseudomonas aeruginosa. Here, we characterize the major P. aeruginosa clone type (mPact) panel. It consists of 20 strains with different origins that cover the major clone types of the species as well as its genomic diversity. This mPact panel shows significant variation in (i) resistance against distinct antibiotics, including several last resort antibiotics, (ii) related traits associated with the response to antibiotics, and (iii) general growth characteristics. We further developed a novel approach that integrates information on resistance, growth, virulence, and life-history characteristics, allowing us to demonstrate the presence of distinct adaptive strategies of the strains that focus either on host interaction or resource processing. In conclusion, the mPact panel provides a manageable number of representative strains for this important pathogen for further in-depth analyses of treatment options and evolutionary dynamics.

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Tueffers, L., Batra, A., Zimmermann, J., Botelho, J., Buchholz, F., Liao, J., Mendoza Mejia, N., Munder, A., Klockgether, J., Tuemmler, B., Rupp, J., Schulenburg, H.. 2024-01-16. Variation in the response to antibiotics and life-history across the major Pseudomonas aeruginosa clone type (mPact) panel. https://doi.org/10.1101/2024.01.15.575732

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