Ligand binding remodels the oligomeric state and active site of Klebsiella pneumoniae azoreductase
Azo dyes are widespread in the environment, and humans ingest a range of these dyes present in food and drugs. The human gut microbiome significantly impacts the fate of ingested azo dyes primarily through the reduction of the azo bond (R-N=N-R'). Flavin-dependent azoreductases have been considered the key enzymatic drivers of this process. To challenge this paradigm, we constructed a sequence…
Klebsiella pneumoniae, a multi-drug resistant bacterium, faces challenges in infection due to nutrient limitations imposed by the host's immune system. This includes iron and zinc deficiencies, which the bacterium must overcome through a process known as nutritional immunity. Siderophores, small molecule molecules that bind iron, are crucial virulence factors in Klebsiella pneumoniae pathogenesis.
The study aimed to understand how multi-drug resistant K. pneumoniae grows in environments limited by zinc. Through unbiased transcriptomics, proteomics, and an arrayed transposon screen, the research found that synthesis and uptake of the siderophore enterobactin are essential for growth in low zinc conditions. Iron-specific chelators did not replicate this growth phenotype, and adding supplemental iron to the growth media could not correct the severe growth defects observed in enterobactin mutant K. pneumoniae experiencing zinc limitation.
The study also revealed that zinc starvation induces enterobactin production independent of the usual zinc uptake regulator (Zur) transcription factor, suggesting an unidentified regulatory mechanism that may help Gram-negative pathogens respond to zinc stress. This research broadens the role of enterobactin beyond iron regulation and identifies a previously unknown connection between iron and zinc homeostasis in Klebsiella pneumoniae.
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