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A Clinically Silent Resistance Phenotype That Promotes Acinetobacter baumannii Survival During Colistin Therapy

Muneer Yaqub1, Namrata Bonde1, Tuhina Maity1

  • 1Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX, USA.

Biorxiv : the Preprint Server for Biology
|February 6, 2026
PubMed

Insights

Clinically silent resistance (CSR) allows Acinetobacter baumannii to survive colistin therapy, even when appearing susceptible. This MIC-independent survival state impacts treatment outcomes for difficult-to-treat infections.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Genomics
  • Pharmacology

Background:

  • Acinetobacter baumannii is a significant cause of multidrug-resistant nosocomial infections, especially ventilator-associated pneumonia.
  • Colistin is a last-resort antibiotic for A. baumannii, but clinical outcomes are variable despite low rates of defined resistance.
  • The bacterial mechanisms enabling survival during colistin treatment are not well understood.

Purpose of the Study:

  • To investigate the genetic basis of colistin response in A. baumannii.
  • To identify bacterial strategies for survival during colistin therapy.
  • To understand the limitations of standard antibiotic susceptibility testing in predicting clinical outcomes.

Main Methods:

  • Supervised machine learning for genomic prioritization of candidate genes.
  • Functional and physiological assays to evaluate bacterial fitness.
  • In vivo studies using a murine pneumonia model.
  • Standardized antibiotic susceptibility testing (MIC determination).

Main Results:

  • Machine learning identified genetic loci associated with colistin survival, many not affecting minimum inhibitory concentration (MIC).
  • A subset of mutants exhibited clinically silent resistance (CSR), maintaining fitness during colistin exposure despite being classified as susceptible.
  • CSR mutants demonstrated enhanced survival and proliferation during colistin therapy in a murine pneumonia model.

Conclusions:

  • Clinically silent resistance (CSR) represents a novel, MIC-independent survival mechanism in A. baumannii.
  • Standard susceptibility testing fails to detect CSR, highlighting limitations in predicting treatment efficacy.
  • Understanding CSR is crucial for improving therapeutic strategies against multidrug-resistant A. baumannii infections.
Keywords:
Acinetobacter baumanniiantibiotic resistancecolistinmachine learningmurine pneumonia models

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