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Genetic alterations in the pmrAB two-component system and lipid A biosynthesis genes of polymyxin-resistant

Nadia El Mrimar1,2, El Mehdi Belouad1,2, Elmostafa Benaissa1,2

  • 11Research Team of Epidemiology and Bacterial Resistance, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat, Morocco.

Acta Microbiologica Et Immunologica Hungarica
|June 5, 2024
PubMed

Insights

Pandrug-resistant Acinetobacter baumannii strains are increasing globally. This study identified novel mutations in colistin resistance genes of two clinical isolates, highlighting the multifactorial nature of antibiotic resistance.

Area of Science:

  • Microbiology
  • Genetics
  • Infectious Diseases

Background:

  • Pandrug-resistant Acinetobacter baumannii poses a significant global health threat.
  • Colistin resistance in A. baumannii is often linked to alterations in lipid A or the pmrAB two-component system.

Purpose of the Study:

  • To investigate the genetic basis of colistin resistance in two clinical isolates of A. baumannii (ABRC1 and ABRC2).
  • To identify novel mutations associated with extreme colistin resistance.

Main Methods:

  • Isolating and characterizing two A. baumannii strains (ABRC1, ABRC2) with high colistin resistance (MIC >256 mg/L).
  • Utilizing PCR and sequencing to analyze colistin resistance genes (pmrA, pmrB, lpxA, lpxC, lpxD, lpsB).
  • Comparing obtained sequences with reference strains (ATCC 19606, 17987).

Main Results:

  • Both strains exhibited novel mutations: N287D in lpxC and E117K in lpxD.
  • ABRC1 showed an additional H200L mutation in pmrA.
  • Both strains shared an A138T mutation in pmrB, and ABRC2 had an R263S substitution in its histidine kinase domain.
  • Three mutations (Q216K, H218G, S219E) were identified in the lpsB gene of both strains.

Conclusions:

  • Colistin resistance in A. baumannii is a complex, multifactorial trait.
  • Novel mutations in lpxC, lpxD, pmrA, pmrB, and lpsB contribute to extreme colistin resistance in clinical isolates.
  • These findings enhance our understanding of antibiotic resistance mechanisms in A. baumannii.
Keywords:
Acinetobacter baumanniicolistin resistantlipid ApmrAB

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