Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire, USA.
mBio. 2024 Sep 11;15(9):e0095624. doi: 10.1128/mbio.00956-24. Epub 2024 Aug 6.
Chronic polymicrobial infections involving and are prevalent, difficult to eradicate, and associated with poor health outcomes. Therefore, understanding interactions between these pathogens is important to inform improved treatment development. We previously demonstrated that is attracted to using type IV pili (TFP)-mediated chemotaxis, but the impact of attraction on growth and physiology remained unknown. Using live single-cell confocal imaging to visualize microcolony structure, spatial organization, and survival of during coculture, we found that interspecies chemotaxis provides a competitive advantage by promoting invasion into and disruption of microcolonies. This behavior renders susceptible to antimicrobials. Conversely, in the absence of TFP motility, cells exhibit reduced invasion of colonies. Instead, builds a cellular barrier adjacent to and secretes diffusible, bacteriostatic antimicrobials like 2-heptyl-4-hydroxyquinoline--oxide (HQNO) into the colonies. Reduced invasion leads to the formation of denser and thicker colonies with increased HQNO-mediated lactic acid fermentation, a physiological change that could complicate treatment strategies. Finally, we show that motility modifications of spatial structure enhance competition against . Overall, these studies expand our understanding of how TFP-mediated interspecies chemotaxis facilitates polymicrobial interactions, highlighting the importance of spatial positioning in mixed-species communities.
The polymicrobial nature of many chronic infections makes their eradication challenging. Particularly, coisolation of and from airways of people with cystic fibrosis and chronic wound infections is common and associated with severe clinical outcomes. The complex interplay between these pathogens is not fully understood, highlighting the need for continued research to improve management of chronic infections. Our study unveils that is attracted to , invades into neighboring colonies, and secretes anti-staphylococcal factors into the interior of the colony. Upon inhibition of motility and thus invasion, colony architecture changes dramatically, whereby is protected from antagonism and responds through physiological alterations that may further hamper treatment. These studies reinforce accumulating evidence that spatial structuring can dictate community resilience and reveal that motility and chemotaxis are critical drivers of interspecies competition.
涉及 和 的慢性多微生物感染普遍存在，难以根除，并与不良健康结果相关。因此，了解这些病原体之间的相互作用对于提供更好的治疗开发信息很重要。我们之前已经证明， 可以通过 IV 型菌毛（TFP）介导的趋化作用被吸引到 ，但是趋化作用对 的生长和生理的影响尚不清楚。使用活的单细胞共焦成像来可视化微菌落结构、空间组织和 在共培养期间的存活，我们发现种间趋化作用通过促进 对 的入侵和破坏提供了 的竞争优势。这种行为使 易受 抗菌药物的影响。相反，在没有 TFP 运动能力的情况下， 细胞对 菌落的入侵减少。相反， 在 菌落旁边建立一个细胞屏障，并将可扩散的抑菌抗菌药物如 2-庚基-4-羟基喹啉-N-氧化物（HQNO）分泌到 菌落中。入侵减少导致形成更密集和更厚的 菌落，HQNO 介导的乳酸发酵增加，这种生理变化可能使治疗策略复杂化。最后，我们表明 运动性改变空间结构会增强对 的竞争。总的来说，这些研究扩展了我们对 TFP 介导的种间趋化作用如何促进多微生物相互作用的理解，突出了在混合物种群落中空间定位的重要性。
许多慢性感染的多微生物性质使得它们的根除具有挑战性。特别是，从囊性纤维化和慢性伤口感染患者的气道中共同分离出 和 是很常见的，并且与严重的临床结果相关。这些病原体之间的复杂相互作用尚未完全了解，这突显了继续研究以改善慢性感染管理的必要性。我们的研究揭示了 被吸引到 中，入侵到相邻的菌落中，并将抗葡萄球菌因子分泌到菌落内部。当抑制 的运动性从而抑制入侵时， 菌落的结构会发生巨大变化， 从而免受 的拮抗作用，通过可能进一步阻碍治疗的生理变化做出反应。这些研究加强了积累的证据，即空间结构可以决定群落的恢复力，并表明运动性和趋化性是种间竞争的关键驱动因素。
