Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 19 min ago
PreprintCC BY-NC-NDbioRxiv

Variable phage susceptibility of Pseudomonas aeruginosa from patients with and without cystic fibrosis following treatment-emergent resistance to ceftolozane-tazobactam

  • N. R. Wallace
  • R. L. DiDonato
  • B. A. Jackson
  • E. G. Kline
  • K. M. Squires
  • A. J. Dorazio
  • R. K. Shields
  • D. Van Tyne1
  1. 1University of Pittsburgh
Read full textPDFDOICite

Abstract

Background: Pseudomonas aeruginosa is a ubiquitous opportunistic bacterial pathogen associated with nosocomial infections and is a leading cause of infection in persons with cystic fibrosis (pwCF). The front-line treatment for multidrug-resistant P. aeruginosa infections is ceftolozane-tazobactam (C/T). While previous research has characterized clinical P. aeruginosa isolates that evolved resistance to C/T, the collateral effect of evolved resistance on susceptibility to bacteriophages has not been explored. Methods: We collected paired P. aeruginosa clinical isolates from 10 pwCF and 18 non-pwCF who developed treatment-emergent C/T resistance. We compared genetic relatedness, acute and chronic virulence phenotypes, and antibiotic and phage susceptibilities between each pair of susceptible baseline and treatment-emergent C/T-resistant isolates. Results: Treatment-emergent C/T-resistant isolates were genetically closely related to baseline isolates in all patients. Virulence phenotypes did not differ between pre- and post-C/T exposure isolates, but isolates from pwCF demonstrated differences in protease production, twitching motility, and amino acid auxotrophy compared to isolates from non-pwCF. Treatment-emergent C/T resistance was associated with increased resistance to ceftazidime and ceftazidime/avibactam, but no other trends in antibiotic or phage susceptibility were detected. Conclusions: Treatment-emergent resistance to C/T does not cause predictable alterations in phage susceptibility across genotypically and phenotypically diverse multidrug-resistant P. aeruginosa clinical isolates.

Related

  1. Disruption of arn lipid A aminoarabinosylation confers AmpCmediated cephalosporin resistance in Pseudomonas aeruginosa
    Madeleine T. Hardie Boys, Samuel J. T. Wardell, Daniel Pletzer
    Communications BiologyPeer-reviewedCC BY 4.0General biologyNatureCrossref
  2. pH-Dependent Evolution of Delafloxacin and Ciprofloxacin Resistance in Pseudomonas aeruginosa from cystic fibrosis (CF) and non-CF-patients
    N. Ireddy, A. Bosch, H. Seth-Smith +2
    bioRxivPreprintAll rights reservedFull textMicrobiologybioRxiv
  3. Bacteriophage susceptibility varies within chronic Pseudomonas aeruginosa lung infections
    N. S. Houpt, J. Vanderwoude, S. P. Diggle +1
    bioRxivPreprintCC BY-NCFull textEvolutionary biologybioRxiv
  4. Genome-wide CRISPRi-seq maps essential-gene contributions to aminoglycoside susceptibility in Pseudomonas aeruginosa
    W. Czeka?a, J. Gawor, R. E. Goitia Camacho +7
    bioRxivPreprintCC BYFull textMicrobiologybioRxiv
  5. Quantifying antibiotic susceptibility and inoculum effects using transient dynamics of Pseudomonas aeruginosa
    Sarah Sundius, Jennifer Farrell, Kelly L Eick +2
    PLOS Computational BiologyPeer-reviewedCC BYFull textEcologyMicrobiologyPLOSEurope PMC

Cite

BibTeXRIS
BibTeX
@misc{wallace2026variable,
  title = {{Variable phage susceptibility of Pseudomonas aeruginosa from patients with and without cystic fibrosis following treatment-emergent resistance to ceftolozane-tazobactam}},
  author = {N. R. Wallace and R. L. DiDonato and B. A. Jackson and E. G. Kline and K. M. Squires and A. J. Dorazio and R. K. Shields and D. Van Tyne},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.03.749285},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749285v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Variable phage susceptibility of Pseudomonas aeruginosa from patients with and without cystic fibrosis following treatment-emergent resistance to ceftolozane-tazobactam
AU  - N. R. Wallace
AU  - R. L. DiDonato
AU  - B. A. Jackson
AU  - E. G. Kline
AU  - K. M. Squires
AU  - A. J. Dorazio
AU  - R. K. Shields
AU  - D. Van Tyne
PY  - 2026
DA  - 2026/09/03
PB  - bioRxiv
DO  - 10.64898/2026.09.03.749285
UR  - https://www.biorxiv.org/content/10.64898/2026.09.03.749285v1
AB  - Background: Pseudomonas aeruginosa is a ubiquitous opportunistic bacterial pathogen associated with nosocomial infections and is a leading cause of infection in persons with cystic fibrosis (pwCF). The front-line treatment for multidrug-resistant P. aeruginosa infections is ceftolozane-tazobactam (C/T). While previous research has characterized clinical P. aeruginosa isolates that evolved resistance to C/T, the collateral effect of evolved resistance on susceptibility to bacteriophages has not been explored. Methods: We collected paired P. aeruginosa clinical isolates from 10 pwCF and 18 non-pwCF who developed treatment-emergent C/T resistance. We compared genetic relatedness, acute and chronic virulence phenotypes, and antibiotic and phage susceptibilities between each pair of susceptible baseline and treatment-emergent C/T-resistant isolates. Results: Treatment-emergent C/T-resistant isolates were genetically closely related to baseline isolates in all patients. Virulence phenotypes did not differ between pre- and post-C/T exposure isolates, but isolates from pwCF demonstrated differences in protease production, twitching motility, and amino acid auxotrophy compared to isolates from non-pwCF. Treatment-emergent C/T resistance was associated with increased resistance to ceftazidime and ceftazidime/avibactam, but no other trends in antibiotic or phage susceptibility were detected. Conclusions: Treatment-emergent resistance to C/T does not cause predictable alterations in phage susceptibility across genotypically and phenotypically diverse multidrug-resistant P. aeruginosa clinical isolates.
ER  -