Proteomic Insights into Strong and Weak Biofilm Formation in Acinetobacter baumannii for Potential Therapeutic Targets

Abstract

Acinetobacter baumannii is notable for its biofilm-forming abilities, which aid in its tolerance to antibiotics, adding to antimicrobial resistance. The clinical isolates present varied biofilm-forming capacity; hence, understanding the molecular determinants that result in strong biofilm development is crucial for drug target identification. This study is the first of its kind to compare proteome profiling of strong and weak biofilm-forming A. baumannii clinical isolates. Comparative proteomic profiling revealed 42 differentially regulated proteins. It was observed that in strong biofilm forming isolate NlpA, uL16, DNA gyrase B, acetyl-CoA carboxylase, and purl etc. were upregulated highlighting a dynamic reprogramming of cellular functions that promotes biofilm formation, stress adaptation, and immune evasion. In contrast, EF-Tu, ribosome hibernation factors, and T6SS components were downregulated, suggesting a lack of biosynthesis and stress adaptability. These findings suggest a metabolic downshift and a possible energy conservation mechanism under conditions less favorable for strong biofilm development. Additionally, several uncharacterized proteins were identified, highlighting potential novel factors in biofilm regulation and virulence that warrant further investigation. The proteomics data correlated with qPCR findings, providing support for the unknown regulators of biofilm formation that were identified in this study. Key proteins such as nlpA, 6,7-dimethyl-8-ribityllumazine synthase and DNA gyrase B emerged as potential therapeutic targets. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/680171v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@1c9b95aorg.highwire.dtl.DTLVardef@a7e781org.highwire.dtl.DTLVardef@14fe64aorg.highwire.dtl.DTLVardef@9804f2_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG