Heffernan James R, Katumba George L, McCoy William H, Henderson Jeffrey P
bioRxiv. 2023 Feb 10:2023.02.09.527953. doi: 10.1101/2023.02.09.527953.
Siderophores are secreted ferric ion chelators used to obtain iron in nutrient-limited environmental niches, including human hosts. While all encode the enterobactin (Ent) siderophore system, isolates from patients with urinary tract infections additionally encode the genetically distinct yersiniabactin (Ybt) siderophore system. To determine whether the Ent and Ybt systems are functionally redundant for iron uptake, we compared growth of different isogenic siderophore biosynthesis mutants in the presence of transferrin, a human iron-binding protein. We observed that the Ybt system does not compensate for loss of the Ent system during siderophore-dependent, low density growth. Using transcriptional and product analysis, we found that this non-redundancy is attributable to a density-dependent transcriptional stimulation cycle in which Ybt assume an additional autoinducer function. These results distinguish the Ybt system as a combined quorum-sensing and siderophore system. These functions may reflect Ybt as a public good within bacterial communities or as an adaptation to confined, subcellular compartments in infected hosts. The efficiency of this arrangement may contribute to the extraintestinal pathogenic potential of and related
Urinary tract infections (UTIs) are one of the most common human bacterial infections encountered by physicians. Adaptations that increase the pathogenic potential of commensal microbes such as are of great interest. One potential adaptation observed in clinical isolates is accumulation of multiple siderophore systems, which scavenge iron for nutritional use. While iron uptake is important for bacterial growth, the increased metabolic costs of siderophore production could diminish bacterial fitness during infections. In a siderophore-dependent growth conditions, we show that the virulence-associated yersiniabactin siderophore system in uropathogenic is not redundant with the ubiquitous enterobactin system. This arises not from differences in iron scavenging activity but because yersiniabactin is preferentially expressed during bacterial crowding, leaving bacteria dependent upon enterobactin for growth at low cell density. Notably, this regulatory mode arises because yersiniabactin stimulates its own expression, acting as an autoinducer in a previously unappreciated quorum-sensing system. This unexpected result connects quorum-sensing with pathogenic potential in and related
铁载体是分泌性铁离子螯合剂，用于在营养有限的环境生态位（包括人类宿主）中获取铁。虽然所有菌株都编码肠杆菌素（Ent）铁载体系统，但从尿路感染患者中分离出的菌株还额外编码基因上不同的耶尔森菌素（Ybt）铁载体系统。为了确定Ent和Ybt系统在铁摄取方面是否功能冗余，我们比较了不同同基因铁载体生物合成突变体在转铁蛋白（一种人类铁结合蛋白）存在下的生长情况。我们观察到，在依赖铁载体的低密度生长过程中，Ybt系统无法补偿Ent系统的缺失。通过转录和产物分析，我们发现这种非冗余性归因于一种密度依赖性转录刺激循环，其中Ybt具有额外的自诱导功能。这些结果将Ybt系统区分为一种群体感应和铁载体的联合系统。这些功能可能反映了Ybt作为细菌群落中的一种公共物品，或者是对感染宿主中受限的亚细胞区室的一种适应。这种安排的效率可能有助于[细菌名称]及相关细菌的肠外致病潜力。
尿路感染（UTIs）是医生遇到的最常见的人类细菌感染之一。增加共生微生物（如[细菌名称]）致病潜力的适应性变化备受关注。在临床分离株中观察到的一种潜在适应性变化是多种铁载体系统的积累，这些系统用于 scavenge iron for nutritional use（此处原文有误，推测应为“获取铁用于营养”）。虽然铁摄取对细菌生长很重要，但铁载体产生增加的代谢成本可能会在感染期间降低细菌的适应性。在依赖铁载体的生长条件下，我们表明尿路致病性[细菌名称]中与毒力相关的耶尔森菌素铁载体系统与普遍存在的肠杆菌素系统并非冗余。这并非源于铁清除活性的差异，而是因为耶尔森菌素在细菌聚集期间优先表达，使得细菌在低细胞密度下依赖肠杆菌素生长。值得注意的是，这种调节模式的出现是因为耶尔森菌素刺激其自身表达，在一个以前未被认识的群体感应系统中充当自诱导剂。这个意外的结果将群体感应与[细菌名称]及相关细菌的致病潜力联系起来。
