Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Infect Immun. 2022 Oct 20;90(10):e0020622. doi: 10.1128/iai.00206-22. Epub 2022 Sep 21.
Colonization of the gastrointestinal (GI) tract by Klebsiella pneumoniae is generally considered asymptomatic. However, gut colonization allows K. pneumoniae to either translocate to sterile site within the same host or transmit through the fecal-oral route to another host. K. pneumoniae gut colonization is poorly understood, but knowledge of this first step toward infection and spread is critical for combatting its disease manifestations. K. pneumoniae must overcome colonization resistance (CR) provided by the host microbiota to establish itself within the gut. One such mechanism of CR is through nutrient competition. Pathogens that metabolize a broad range of substrates have the ability to bypass nutrient competition and overcome CR. Herein, we demonstrate that in response to mucin-derived fucose, the conserved fucose metabolism operon () of K. pneumoniae is upregulated in the murine gut, and we subsequently show that fucose metabolism promotes robust gut colonization. Growth studies using cecal filtrate as a proxy for the gut lumen illustrate the growth advantage that the operon provides K. pneumoniae. We further show that fucose metabolism allows K. pneumoniae to be competitive with a commensal Escherichia coli isolate (Nissle). However, Nissle is eventually able to outcompete K. pneumoniae, suggesting that it can be utilized to enhance CR. Finally, we observed that fucose metabolism positively modulates hypermucoviscosity, autoaggregation, and biofilm formation but not capsule biogenesis. Together, these insights enhance our understanding of the role of alternative carbon sources in K. pneumoniae gut colonization and the complex relationship between metabolism and virulence in this species.
肺炎克雷伯菌（Klebsiella pneumoniae）在胃肠道（GI）的定植通常被认为是无症状的。然而，肠道定植使肺炎克雷伯菌能够在同一宿主内转移到无菌部位，或通过粪-口途径传播到另一个宿主。肺炎克雷伯菌肠道定植的机制尚不清楚，但了解这一感染和传播的第一步对于控制其疾病表现至关重要。肺炎克雷伯菌必须克服宿主微生物群提供的定植抗性（CR）才能在肠道内定植。CR 的一种机制是通过营养竞争。能够代谢广泛底物的病原体具有绕过营养竞争和克服 CR 的能力。在此，我们证明，响应粘蛋白衍生的岩藻糖，肺炎克雷伯菌的保守岩藻糖代谢操纵子（）在鼠肠道中上调，我们随后表明，岩藻糖代谢促进了强大的肠道定植。使用盲肠滤液作为肠道腔的替代物进行的生长研究说明了 操纵子为肺炎克雷伯菌提供的生长优势。我们进一步表明，岩藻糖代谢使肺炎克雷伯菌能够与共生的大肠杆菌分离株（Nissle）竞争。然而，Nissle 最终能够战胜肺炎克雷伯菌，这表明它可以被利用来增强 CR。最后，我们观察到岩藻糖代谢积极调节高粘液性、自动聚集和生物膜形成，但不调节荚膜生物发生。总之，这些发现增强了我们对替代碳源在肺炎克雷伯菌肠道定植中的作用以及该物种代谢和毒力之间复杂关系的理解。
