Characterization of the ferric uptake regulator Va Fur regulon and its role in Vibrio anguillarum pathogenesis

• Published in: Applied and environmental microbiology 2024-11, Vol.90 (11), p.e0150824
• Main Authors: Li, Yingjie, Yu, Xinran, Li, Peng, Li, Xin, Wang, Lushan
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Fish Diseases - microbiology; Gene Expression Regulation, Bacterial; Iron - metabolism; Regulon; Repressor Proteins; Type VI Secretion Systems - genetics; Type VI Secretion Systems - metabolism; Vibrio - genetics; Vibrio - metabolism; Vibrio - pathogenicity; Vibrio Infections - microbiology; Virulence; Virulence Factors - genetics; Virulence Factors - metabolism
• ISSN: 0099-2240; 1098-5336
• DOI: 10.1128/aem.01508-24

The Gram-negative marine bacterium is able to cause vibriosis with hemorrhagic septicemia in many fish species, and iron acquisition is a critical step for virulence. Despite the fact that genes specific to certain processes of iron transport have been studied, the iron-regulated circuits of the strains remain poorly understood. In this study, we showed that in strain 775, iron could affect the expression of a number of critical metabolic pathways and virulence factors. The global iron uptake regulator Fur is the major actor to control these processes for the bacterium to respond to different iron conditions. A Fur binding motif was identified to distinguish directly and indirectly regulated targets. The absence of Fur resulted in the aberrant expression of most iron acquisition determinants under rich-iron conditions. A similar regulation pattern was also observed in the transcription of genes coding for the type VI secretion system. The expression of peroxidase genes is positively controlled by Fur to prevent iron toxicity, and the deletion of caused impaired growth in the presence of iron and H O . Fur also upregulates some virulence factors under limited-iron conditions, including metalloprotease EmpA and motility, which are likely critical for the high virulence of 775. The deletion of Fur led to reduced swimming motility and decreased extracellular protease activity under limited-iron conditions, thereby leading to attenuated pathogenicity. Our study provides more evidence to better understand the Fur regulon and its role in the pathogenesis of .IMPORTANCEVibriosis, the most common disease caused by marine bacteria belonging to the genus , leads to massive mortality of economical aquatic organisms in Asia. Iron is one of the most important trace elements, and its acquisition is a critical battle occurring between the host and the pathogen. However, excess iron is harmful to cells, so iron utilization needs to be strictly controlled to adapt to different conditions. This process is mediated by the global iron uptake regulator Fur, which acts as a repressor when iron is replete. On the other hand, free iron in the host is limited, so the reduced virulence of the Δ mutant should not be directly caused by abnormally regulated iron uptake. The significance of this work lies in uncovering the mechanism by which the deletion of Fur causes reduced virulence in and identifying the critical virulence factors that function under limited-iron conditions.