Molecular Signatures of Pyomelanin Production in MDR <i>Acinetobacter baumannii</i> : A Proteomic Perspective

<i>Acinetobacter baumannii</i> causes severe nosocomial opportunistic infections and is rapidly emerging as a global health threat. Despite reports on the rare pigment production in <i>A. baumannii</i> and genomic insights, the molecular mechanisms and their functional implications in virulence driving this rare phenotype remain inadequately characterized. Recognizing this limitation, we performed comparative proteomic profiling of six clinical pyomelanin-producing <i>A. baumannii</i> isolates with four nonpyomelanin-producing isolates. Among the total proteins detected, 66 were up-regulated, and 52 were down-regulated, forming a highly interactive regulatory network in pyomelanin production. Comparative proteomics identified perturbed pathways, including activation of amino acid and pyruvate metabolism, cell membrane biosynthesis, stress response, and virulence factor association, such as biofilm formation, T6 secretion system, highlighting their roles in host adaptation and pathogenicity. Nevertheless, no significant change was noticed in terms of adhesion, cytotoxicity in A549 cell lines, and virulence in <i>Galleria mellonella</i>. Overall, this study expands our understanding of pyomelanin-driven proteomic perturbations in clinical isolates of <i>A. baumannii</i> and helps us to monitor the marked alterations in pigment-producing phenotype, which may provide critical insights for diagnostic and treatment approaches.