Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia.
Department of Bioengineering, University of California, San Diego, San Diego, California 92093, USA.
Genome Res. 2022 May;32(5):1004-1014. doi: 10.1101/gr.276289.121. Epub 2022 Mar 11.
The species complex (KpSC) is a set of seven 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 research community.
种系复合体（KpSC）是一组七种在各种生境中发现的分类群，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，以提供新的控制策略。我们汇集了来自各种生境的 37 株已测序的 KpSC 分离株，代表了所有七种分类群。我们为所有 37 株分离株生成了特定菌株的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。对模型进行了校对，并使用 94 种底物的匹配表型生长数据评估了其准确性（中位数准确性为 96%）。我们探索了物种特异性的生长能力，并通过在 145 种核心碳底物上进行生长模拟，检查了所有可能的单基因缺失的影响。这些分析揭示了种内和种间的多个菌株特异性差异，并强调了在探索 KpSC 代谢时选择多样化菌株的重要性。这一组多样化的高度准确的 GEM 可用于为新型药物设计提供信息，增强基因组分析，并确定新的毒力和耐药决定因素。我们设想，这 37 个经过精心编辑的特定菌株的 GEM，涵盖了 KpSC 的所有七种分类群，为研究界提供了宝贵的资源。
