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Case Commentary: When one target is not enough-PBP3 insertions and target redundancy in Escherichia coli

Madison E Stellfox1, Yohei Doi1,2

  • 1Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.

Antimicrobial Agents and Chemotherapy
|April 6, 2026
PubMed

Insights

Penicillin-binding protein 3 (PBP3) insertions in Escherichia coli reduce susceptibility to beta-lactam antibiotics, complicating treatment. Combination therapy with imipenem-relebactam and aztreonam successfully treated a patient with NDM-producing E. coli.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • Penicillin-binding protein 3 (PBP3) insertions in Escherichia coli can confer resistance to beta-lactam antibiotics.
  • This resistance mechanism complicates treatment, especially when co-occurring with New Delhi metallo-beta-lactamase (NDM) production.

Purpose of the Study:

  • To highlight the clinical impact of PBP3 insertions in Escherichia coli.
  • To present a successful treatment strategy for a complex case of beta-lactam resistant E. coli.

Main Methods:

  • Case report of a patient with NDM-producing Escherichia coli.
  • Clinical assessment of treatment response to imipenem-relebactam plus aztreonam.

Main Results:

  • PBP3 insertions significantly reduced susceptibility to key beta-lactam agents.
  • Clinical improvement was achieved with the combination therapy of imipenem-relebactam and aztreonam.
  • Targeting multiple penicillin-binding proteins can overcome functional redundancy in resistance.

Conclusions:

  • PBP3-mediated resistance is clinically relevant in Gram-negative pathogens.
  • Novel treatment strategies are needed to address complex beta-lactam resistance.
  • Combination therapy targeting multiple penicillin-binding proteins shows promise for treating resistant infections.
Keywords:
PBP insertionsbeta-lactam resistancetarget redundancy

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