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<p><i>Klebsiella michiganensis</i>, an emerging multidrug-resistant pathogen, poses a significant public health threat. This study employed subtractive genomics to identify potential therapeutic targets in <i>K. michiganensis</i> THO-011. From 4,024 predicted open reading frames, we identified non-redundant, human non-homologous proteins and analyzed them for essentiality, subcellular localization, and metabolic pathway involvement. Two promising druggable targets, WP_004097788.1 and WP_219541799, vital for bacterial survival, were identified. Using AlphaFold-predicted structures, virtual screening of 10,000 natural compounds from the LOTUS database, alongside DrugBank controls, identified LTS0037797 and LTS0037810 as top inhibitors. Glide Gscores ranked these compounds, with validation via MM-GBSA binding energy and molecular dynamics simulations confirming their stability and binding efficacy. These findings highlight novel therapeutic strategies against <i>K. michiganensis</i>, with further in vitro studies necessary to advance these inhibitors to clinical application.</p>

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Subtractive proteomics and molecular docking identify therapeutic targets and drug candidates in drug resistant Klebsiella Michiganensis THO-011

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月3日

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  • Abdullah R. Alanzi,
  • Ahmad Z. Alanazi,
  • Khalid Alhazzani,
  • Munawar Abbas

摘要

Klebsiella michiganensis, an emerging multidrug-resistant pathogen, poses a significant public health threat. This study employed subtractive genomics to identify potential therapeutic targets in K. michiganensis THO-011. From 4,024 predicted open reading frames, we identified non-redundant, human non-homologous proteins and analyzed them for essentiality, subcellular localization, and metabolic pathway involvement. Two promising druggable targets, WP_004097788.1 and WP_219541799, vital for bacterial survival, were identified. Using AlphaFold-predicted structures, virtual screening of 10,000 natural compounds from the LOTUS database, alongside DrugBank controls, identified LTS0037797 and LTS0037810 as top inhibitors. Glide Gscores ranked these compounds, with validation via MM-GBSA binding energy and molecular dynamics simulations confirming their stability and binding efficacy. These findings highlight novel therapeutic strategies against K. michiganensis, with further in vitro studies necessary to advance these inhibitors to clinical application.