Molecular Signatures of Pyomelanin Production in MDR Acinetobacter baumannii: A Proteomic Perspective

Acinetobacter baumannii causes severe
nosocomial opportunistic infections and is rapidly emerging as a global
health threat. Despite reports on the rare pigment production in A. baumannii 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 A. baumannii 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 Galleria mellonella. Overall, this
study expands our understanding of pyomelanin-driven proteomic perturbations
in clinical isolates of A. baumannii and helps us to monitor the marked alterations in pigment-producing
phenotype, which may provide critical insights for diagnostic and
treatment approaches.