Isoelectric point stabilization and protein mass compression are associated with antimicrobial resistance in the...

The genus Acinetobacter is widely regarded as a major reservoir of antimicrobial resistance (AMR); however, the evolutionary distribution of resistance across the genus remains unclear. This study aimed to investigate phylogenomic structure and associated proteomic features underlying AMR distribution.

A total 67 genomes including 65 representative Acinetobacter species, one additional Acinetobacter baumannii ATCC 19606 reference genome and Alkanindiges hydrocarboniclasticus as the outgroup were analyzed using a 174-gene core genome phylogeny. Resistome profiling was performed using homology-based screening, and proteome-wide properties, including isoelectric point (pI), molecular weight, and protein count, were statistically compared between antibiotic resistance gene (ARG) positive and ARG negative groups based on Resfinder Screening.

Phylogenetic analysis revealed a clear partitioning into ARG positive and ARG negative clades with 28 lineages lacking detectable AMR determinants. A Chi-square test confirmed a significant association between evolutionary clades and resistome distribution (X2 = 29.69, p = 0.0052). While global pI values remained conserved, ARG positive lineages showed significantly reduced pI variance (p = 0.0054). Additionally, ARG positive lineages exhibited expanded proteomes (p < 0.0001) coupled with reduced average molecular weight (p = 0.0056), indicating a shift toward a more compact proteome architecture.

These findings suggest that AMR evolution in Acinetobacter is associated with both genomic partitioning and distinct proteomic patterns. The presence of ARG-negative lineages and coordinated differences in proteome size, average molecular weight, and pI variance highlight the potential role of biophysical properties in shaping AMR-associated genomic variation, while the conserved global pI indicates that these differences do not reflect a shift in overall proteome pI. These findings provide a framework for further investigating biophysical features associated with emerging ARG-positive lineages.