Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hannover, New Hampshire, USA.
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA.
J Bacteriol. 2020 Mar 26;202(8). doi: 10.1128/JB.00559-19.
Cystic fibrosis (CF) patients chronically infected with both and have worse health outcomes than patients who are monoinfected with either or We showed previously that mucoid strains of can coexist with due to the transcriptional downregulation of several toxic exoproducts typically produced by , including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline -oxide). Here, we demonstrate that exogenous alginate protects from in both planktonic and biofilm coculture models under a variety of nutritional conditions. protection in the presence of exogenous alginate is due to the transcriptional downregulation of , a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS ( quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid with nonmucoid strains can mitigate the killing of by the nonmucoid strain of , indicating that the mechanism that we describe here may function in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the -protective effects of mucoidy in a strain-specific manner. CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are and , with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote - coexistence, despite evidence that kills when these organisms are cocultured Thus, a better understanding of - interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.
囊性纤维化 (CF) 患者长期同时感染 和 ，其健康状况比单纯感染 或 更差。我们之前曾表明，由于通常由 产生的几种毒性外产物的转录下调，包括铁载体、鼠李糖脂和 HQNO（2-庚基-4-羟基喹啉-N-氧化物），黏液型 株可以与 共存。在这里，我们证明了在各种营养条件下，外源性藻酸盐在浮游生物和生物膜共培养模型中均可保护 免受 的侵害。在存在外源性藻酸盐的情况下， 的保护归因于 的转录下调，这是产生铁螯合铁载体吡咯并喹啉醌 (pyoverdine) 以及 PQS（喹诺酮信号）(2-庚基-3,4-二羟基喹啉）群体感应系统下调所必需的基因。外源性藻酸盐的影响与内源性藻酸盐的产生无关。我们进一步证明，黏液型 与非黏液型 菌株的共培养可以减轻非黏液型菌株对 的杀伤作用，表明我们在这里描述的机制可能在混合感染的情况下发挥作用。最后，我们研究了一组保留在晚期杀伤 能力的黏液型临床分离株，并表明每个菌株都有独特的表达谱，表明黏液型分离株可以以菌株特异性的方式克服黏液型的保护作用。囊性纤维化患者长期受到多微生物群落的感染。感染 CF 患者肺部的两种主要细菌病原体是 和 ，约 30%的患者同时感染这两种物种。这种合并感染的个体比单纯感染的患者预后更差，而且这两种物种都存在于相同的物理空间内。已经证明，尽管有证据表明当这些生物体共培养时， 会杀死 ，但各种宿主和环境因素都促进了 的共存。因此，更好地了解 之间的相互作用，特别是这些微生物能够在接近物理空间共存的机制，将导致对慢性多微生物感染的治疗方法更加明智。
