Modulation of Iron-Uptake Systems by a Mutation of luxS Encoding an Autoinducer-2 Synthase in Vibrio vulnificus

Abstract

Vibrio vulnificus is a Gram-negative halophilic bacterium that causes primary septicemia and necrotizing wound infections with a high mortality rate in susceptible individuals. V. vulnificus possesses a variety of virulence factors, including acid neutralization, capsular polysaccharide expression, iron acquisition, cytotoxicity, motility, and expression of proteins involved in attachment and adhesion. The concerted expression of the virulence factors is likely required for pathogenesis and appears to be under the control of global regulators. 1)V. vulnificus possesses multiple iron-uptake systems (IUSs), all of which are being considered as virulence factors.1) V. vulnificus produces a catechol-type siderophore (called vulnibactin) and hydroxamate siderophore for iron acquisition in iron-deficient conditions.2) The ability of V. vulnificus to utilize transferrin-bound iron is mainly dependent on the activity of vulnibactin or vulnibactin receptor (VuuA)-mediated IUS.3-5) V. vulnificus also possesses a heme receptor (HupA) for direct acquisition of iron from various heme proteins.6) In addition, V. vulnificus can utilize heterologous siderophores, including deferoxamine and Escherichia coli aerobactin, via DesA-and IutA-mediated IUSs.7-9) These IUSs are all negatively regulated by iron via ferric uptake regulator (Fur), a transcriptional repressor. [4][5][6][7][8][9] Most recently, it has been demonstrated that the IUSs are under the positive control of cyclic AMP-receptor protein. 10,11) Quorum sensing (QS) is a process of bacterial cell-to-cell communication involving the production and detection of extracellular signaling molecules called autoinducers (AIs), and allows populations of bacteria to collectively control gene expression, and thus synchronize group behavior for better survival. Particularly, AI-2 is considered to be universal language for interspecies communication.12,13) V. vulnificus harbors the AI-2-mediated QS system (AI-2-QSS), which is one of the LuxS/LuxR-type systems.14) AI-2-QSS can be simplified into the two steps, AI-2 production and AI-2 signaling. AI-2 synthesis is under the control of LuxS, which is also a metabolic enzyme responsible for methionine synthesis. 15)AI-2 signaling is transmitted to SmcR (LuxR) via LuxO and LuxT.16) As in other pathogens, 12,13) AI-2-QSS affects the expression of several virulence or survival factors in V. vulnificus. 17,18) A direct link between QSS and IUS expression has been documented in Pseudomonas aeruginosa.19) Various and intricate links between LuxS or AI-2-QSS and IUS expression have been reported in some bacteria. [20][21][22][23][24][25][26] However, the presence of such links remains undetermined in V. vulnificus. AI-2 production through the enzymatic action of LuxS is the prerequisite step for AI-2 signaling. Therefore, we first investigated the effect of a luxS mutation on vuuA, iutA or hupA expression in this study. MATERIALS AND METHODSBacterial Strains, Plasmids, Primers, Media, and Reagents The bacterial strains, plasmids, and primers u...

LuxS Mediates Iron-Dependent Biofilm Formation, Competence, and Fratricide in Streptococcus pneumoniae

“…Moreover, the supplementation of media with (25). Similarly, mutation of luxS in Vibrio vulnificus increased the expression of the vulnibactin receptor but decreased the expression of receptors for aerobactin and heme (28). However, in contrast to the present study, the effect of the luxS mutations on actual cellular iron levels in these organisms was not determined.…”

Regulation of iron-uptake systems in Vibrio vulnificus, a ferrophilic bacterium

“…Therefore, Fur is the key repressor that prevents the overexpression of vvsAB in response to Fe in Fe-sufficient environments, whereas SmcR is another key repressor that prevents the overexpression of vvsAB in response to bacterial density in Fe-deficient environments. In another study [69], a mutation in luxS slightly decreased the expression of vuuA but slightly increased the expression of iutA and hupA in V. vulnificus (Figs. 2, 3 and 5).…”

Vibrio Iron Transport: Evolutionary Adaptation to Life in Multiple Environments

“…Under high-iron conditions, Fur repressed vvsA transcription, while in low-iron environments, SmcR regulated the expression of the siderophore biosynthesis genes (245). Using a luxS mutant defective in the synthesis of autoinducer 2 (AI-2), Kim and Shin observed an increase in the synthesis of the siderophore receptors for aerobactin (IutA) and heme (HupA), suggesting that they are also repressed by quorum sensing (246). Additional studies revealed a more complex connection between iron and quorum sensing (247).…”