Mugni Sabrina Laura, Ambrosis Nicolás, O Toole George A, Sisti Federico, Fernández Julieta
CCT La Plata. CONICET. Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, UNLP, Instituto de Biotecnología y Biología Molecular, La Plata, Buenos Aires Province, Argentina.
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
J Bacteriol. 2025 Apr 17;207(4):e0044524. doi: 10.1128/jb.00445-24. Epub 2025 Mar 26.
a respiratory pathogen capable of infecting various mammals, including humans, is associated with chronic infections. can form biofilm-like structures , providing tolerance against environmental stresses. Recent studies have highlighted the role of cyclic diguanylate monophosphate (c-di-GMP) in this process : elevated c-di-GMP levels stimulate biofilm formation, whereas phosphodiesterase (PDE) activation reduces biofilms. Respiratory secretions, which contain albumin and calcium at higher concentrations than standard growth media, promote an increase in the amount and extracellular localization of the adenylate cyclase toxin (ACT), an important virulence factor of . Secreted ACT, present in the extracellular medium or attached to the outer membrane, inhibits biofilm formation. Based on these observations, we hypothesized that serum albumin and calcium together inhibit biofilm formation and explored the potential role of c-di-GMP in this process. Our findings suggest that serum albumin and calcium inhibit biofilm formation through two potentially independent mechanisms: one involving ACT secretion and another promoting c-di-GMP degradation. In the presence of albumin and calcium, intracellular levels of c-di-GMP were reduced, and specific PDEs appear to be involved in this process. In addition, albumin and calcium stimulated the secretion of the adhesin BrtA. This study contributes to the understanding of the mechanisms governing biofilm formation and its modulation by host factors.IMPORTANCE, a respiratory pathogen capable of infecting various mammals, forms biofilms that enhance its ability to withstand environmental stresses. This study reveals that host-derived factors, specifically serum albumin and calcium, inhibit biofilm formation through two independent mechanisms: increasing adenylate cyclase toxin secretion and promoting the degradation of cyclic diguanylate monophosphate (c-di-GMP), a key biofilm regulator. These findings provide insights into how host conditions influence biofilm dynamics, shedding light on the complex interactions between pathogen and host that contribute to infection persistence. Understanding these mechanisms may inform strategies to mitigate chronic infections caused by .
一种能够感染包括人类在内的多种哺乳动物的呼吸道病原体与慢性感染有关。它能够形成类似生物膜的结构，从而耐受环境压力。最近的研究突出了环二鸟苷单磷酸（c-di-GMP）在此过程中的作用：c-di-GMP水平升高会刺激生物膜形成，而磷酸二酯酶（PDE）的激活则会减少生物膜。呼吸道分泌物中白蛋白和钙的浓度高于标准生长培养基，会促使腺苷酸环化酶毒素（ACT）的量增加及其细胞外定位，ACT是该病原体的一种重要毒力因子。分泌型ACT存在于细胞外培养基中或附着在外膜上，会抑制生物膜形成。基于这些观察结果，我们推测血清白蛋白和钙共同抑制生物膜形成，并探讨了c-di-GMP在此过程中的潜在作用。我们的研究结果表明，血清白蛋白和钙通过两种潜在独立的机制抑制生物膜形成：一种涉及ACT分泌，另一种促进c-di-GMP降解。在有白蛋白和钙的情况下，细胞内c-di-GMP水平降低，并且特定的PDE似乎参与了这一过程。此外，白蛋白和钙刺激了黏附素BrtA的分泌。这项研究有助于理解控制该病原体生物膜形成及其受宿主因子调节的机制。重要的是，一种能够感染多种哺乳动物的呼吸道病原体形成生物膜，增强了其耐受环境压力的能力。这项研究表明，宿主来源的因子，特别是血清白蛋白和钙，通过两种独立的机制抑制生物膜形成：增加腺苷酸环化酶毒素分泌和促进环二鸟苷单磷酸（c-di-GMP，一种关键的生物膜调节因子）的降解。这些发现为宿主条件如何影响该病原体生物膜动态提供了见解，揭示了病原体与宿主之间导致感染持续存在的复杂相互作用。了解这些机制可能为减轻由该病原体引起的慢性感染的策略提供依据。
