Identifying how drug efflux mechanisms impact Acinetobacter baumannii evolutionary paths to ciprofloxacin resistance

Authors

  • Naomi Bastiampillai University of Pittsburgh
  • Alecia Rokes Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Evolutionary Biology and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
  • Vaughn Cooper Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Evolutionary Biology and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

DOI:

https://doi.org/10.5195/pur.2024.81

Abstract

Acinetobacter baumannii is a multi-drug resistant pathogen commonly found in clinical settings. This pathogen frequently uses efflux pumps to mitigate antibiotic treatment stress and eliminate the drug. When A. baumannii is exposed to antibiotics, it often develops mutations in the efflux pump regulator genes, causing an increase in efflux pump production. We hypothesize that efflux is a key pathway that leads to treatment failure in A. baumannii infections. The extent to which increasing drug efflux impacts other cellular functions remains unknown. To identify how efflux pump mutations impact growth, resistance, and evolvability, wildtype A. baumannii laboratory strain 17978UN, along with four mutants of this strain, each with a single nucleotide polymorphism (SNP) in an efflux pump regulator (adeL L341R, adeN I49N, adeR D23Y, and adeS R152S), were propagated in the presence of antibiotic and an efflux pump inhibitor to place selective pressure on the isolates. SNPs increase the production of efflux pumps; inhibiting efflux ability will determine if the effect of each SNP is nullified. All evolved populations demonstrated differences in fitness and antibiotic resistance in comparison to their respective ancestors; the extent of adaptation affecting each phenotype was highly dependent on the regulator that was mutated. Counterintuitively, efflux inhibitors also placed stress on wild-type A. baumannii which leads to antibiotic resistance. These results demonstrate that efflux regulator mutations can influence population adaptability and cause treatment failure. Understanding the role that different efflux systems play in treatment failure and drug resistance evolution will be instrumental in developing treatment strategies that hinder the development of antibiotic resistance.

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Published

2024-11-12

How to Cite

Bastiampillai, N., Rokes, A., & Cooper, V. (2024). Identifying how drug efflux mechanisms impact Acinetobacter baumannii evolutionary paths to ciprofloxacin resistance. Pittsburgh Undergraduate Review, 3(2), 1–22. https://doi.org/10.5195/pur.2024.81

Issue

Vol. 3 No. 2 (2024): Pittsburgh Undergraduate Review

Section

Research

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Copyright (c) 2024 Naomi Bastiampillai, Alecia Rokes, Vaughn Cooper

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