The Emerging Threat of Acinetobacter baumannii Carbapenem Resistance: Molecular Pathways, Genomic Adaptations, and Novel Therapeutic Strategies

Rana  Jalal Shaker

doi:10.17605/cajmns.v6i3.2810

Rana Jalal Shaker Department of Biological Sciences, Tikrit University, Tikrit, Iraq

DOI: https://doi.org/10.17605/cajmns.v6i3.2810

Keywords: Acinetobacter Baumannii, Carbapenem Resistance, ST2 Clone, Blaoxa-23, Blandm-1, Biofilm Formation

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a critical threat in healthcare settings, particularly in intensive care units (ICUs), where its association with ventilator-associated pneumonia and bloodstream infections drives high mortality rates, this study integrates clinical, genomic, and phenotypic analyses of 200 CRAB isolates to unravel the molecular drivers of resistance and virulence. Whole-genome sequencing revealed the dominance of the ST2 clone (Pasteur scheme), harboring blaOXA-23 on the IncH-type plasmid GR6 and chromosomal mutations in ompA and adeABC efflux pumps, which correlated with pan-drug resistance and robust biofilm formation. Strong biofilm producers (OD570 ≥1.0) exhibited 5.2-fold greater survival under meropenem stress (64 µg/mL) and a 65% mortality rate in patients, underscoring biofilm’s role as a resistance amplifier. Molecular screening identified blaOXA-23 in 80% of isolates, while blaNDM-1 (35%) was linked to environmental persistence and cefiderocol resistance. In vivo models demonstrated the efficacy of colistin-meropenem combination therapy, reducing mortality from 100% to 30% in Galleria Mellon Ella. These findings emphasize the urgent need for genomic surveillance of high-risk clones and biofilm-targeted therapeutic strategies to mitigate the CRAB crisis.

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