The Klebsiella pneumoniae species complex (KpSC) is a set of seven Klebsiella taxa that are found in a variety of niches and are an important cause of opportunistic health care–associated infections in humans. Because of increasing rates of multi-drug resistance within the KpSC, there is a growing interest in better understanding the biology and metabolism of these organisms to inform novel control strategies. We collated 37 sequenced KpSC isolates isolated from a variety of niches, representing all seven taxa. We generated strain-specific genome-scale metabolic models (GEMs) for all 37 isolates and simulated growth phenotypes on 511 distinct carbon, nitrogen, sulfur, and phosphorus substrates. Models were curated and their accuracy was assessed using matched phenotypic growth data for 94 substrates (median accuracy of 96%). We explored species-specific growth capabilities and examined the impact of all possible single gene deletions using growth simulations in 145 core carbon substrates. These analyses revealed multiple strain-specific differences, within and between species, and highlight the importance of selecting a diverse range of strains when exploring KpSC metabolism. This diverse set of highly accurate GEMs could be used to inform novel drug design, enhance genomic analyses, and identify novel virulence and resistance determinants. We envisage that these 37 curated strain-specific GEMs, covering all seven taxa of the KpSC, provide a valuable resource to the Klebsiella research community.

中文翻译：

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克雷伯氏菌代谢模型的精选集合揭示了可变的底物使用和基因必要性


肺炎克雷伯菌复合体 (KpSC) 是一组七种克雷伯菌类群，存在于各种生态位中，是人类机会性医疗保健相关感染的重要原因。由于 KpSC 内的多药耐药率不断增加，人们越来越有兴趣更好地了解这些生物体的生物学和代谢，从而为新的控制策略提供信息。我们整理了从各种生态位中分离出来的 37 个已测序的 KpSC 分离株，代表了所有七个类群。我们为所有 37 个分离株生成了菌株特异性基因组规模代谢模型 (GEM)，并在 511 种不同的碳、氮、硫和磷底物上模拟了生长表型。设计模型并使用 94 种底物的匹配表型生长数据评估其准确性（中位准确度为 96%）。我们探索了物种特异性的生长能力，并使用 145 个核心碳底物的生长模拟检查了所有可能的单基因缺失的影响。这些分析揭示了物种内部和物种之间的多种菌株特异性差异，并强调了在探索 KpSC 代谢时选择多种菌株的重要性。这套多样化的高度准确的 GEM 可用于为新药物设计提供信息、增强基因组分析并识别新的毒力和耐药性决定因素。我们设想这 37 个精选的菌株特异性 GEM，涵盖 KpSC 的所有七个分类单元，为克雷伯氏菌研究界提供宝贵的资源。