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1. LuxT Is a Global Regulator of Low-Cell-Density Behaviors, Including Type III Secretion, Siderophore Production, and Aerolysin Production, in Vibrio harveyi

   https://doi.org/10.1128/mbio.03621-21  

   Eickhoff, Michaela J.; Fei, Chenyi; Cong, Jian-Ping; Bassler, Bonnie L. (February 2022, mBio)

   Storz, Gisela (Ed.)

   ABSTRACT Quorum sensing (QS) is a chemical communication process in which bacteria produce, release, and detect extracellular signaling molecules called autoinducers. Via combined transcriptional and posttranscriptional regulatory mechanisms, QS allows bacteria to collectively alter gene expression on a population-wide scale. Recently, the TetR family transcriptional regulator LuxT was shown to control Vibrio harveyi qrr 1, encoding the Qrr1 small RNA that functions at the core of the QS regulatory cascade. Here, we use RNA sequencing to reveal that, beyond the control of qrr 1, LuxT is a global regulator of 414 V. harveyi genes, including those involved in type III secretion, siderophore production, and aerolysin toxin biosynthesis. Importantly, LuxT directly represses swrZ , encoding a GntR family transcriptional regulator, and LuxT control of type III secretion, siderophore, and aerolysin genes occurs by two mechanisms, one that is SwrZ dependent and one that is SwrZ independent. All of these target genes specify QS-controlled behaviors that are enacted when V. harveyi is at low cell density. Thus, LuxT and SwrZ function in parallel with QS to drive particular low-cell-density behaviors. Phylogenetic analyses reveal that luxT is highly conserved among Vibrionaceae , but swrZ is less well conserved. In a test case, we find that in Aliivibrio fischeri , LuxT also represses swrZ . SwrZ is a repressor of A. fischeri siderophore production genes. Thus, LuxT repression of swrZ drives the activation of A. fischeri siderophore gene expression. Our results indicate that LuxT is a major regulator among Vibrionaceae , and in the species that also possess swrZ , LuxT functions with SwrZ to control gene expression. IMPORTANCE Bacteria precisely tune gene expression patterns to successfully react to changes that occur in the environment. Defining the mechanisms that enable bacteria to thrive in diverse and fluctuating habitats, including in host organisms, is crucial for a deep understanding of the microbial world and also for the development of effective applications to promote or combat particular bacteria. In this study, we show that a regulator called LuxT controls over 400 genes in the marine bacterium Vibrio harveyi and that LuxT is highly conserved among Vibrionaceae species, ubiquitous marine bacteria that often cause disease. We characterize the mechanisms by which LuxT controls genes involved in virulence and nutrient acquisition. We show that LuxT functions in parallel with a set of regulators of the bacterial cell-to-cell communication process called quorum sensing to promote V. harveyi behaviors at low cell density. 

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2. Petrobactin, a siderophore produced by Alteromonas, mediates community iron acquisition in the global ocean

   https://doi.org/10.1038/s41396-021-01065-y  

   Manck, Lauren E.; Park, Jiwoon; Tully, Benjamin J.; Poire, Alfonso M.; Bundy, Randelle M.; Dupont, Christopher L.; Barbeau, Katherine A. (February 2022, The ISME Journal)

   Abstract It is now widely accepted that siderophores play a role in marine iron biogeochemical cycling. However, the mechanisms by which siderophores affect the availability of iron from specific sources and the resulting significance of these processes on iron biogeochemical cycling as a whole have remained largely untested. In this study, we develop a model system for testing the effects of siderophore production on iron bioavailability using the marine copiotroph Alteromonas macleodii ATCC 27126. Through the generation of the knockout cell line Δ asbB ::km r , which lacks siderophore biosynthetic capabilities, we demonstrate that the production of the siderophore petrobactin enables the acquisition of iron from mineral sources and weaker iron-ligand complexes. Notably, the utilization of lithogenic iron, such as that from atmospheric dust, indicates a significant role for siderophores in the incorporation of new iron into marine systems. We have also detected petrobactin, a photoreactive siderophore, directly from seawater in the mid-latitudes of the North Pacific and have identified the biosynthetic pathway for petrobactin in bacterial metagenome-assembled genomes widely distributed across the global ocean. Together, these results improve our mechanistic understanding of the role of siderophore production in iron biogeochemical cycling in the marine environment wherein iron speciation, bioavailability, and residence time can be directly influenced by microbial activities. 

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3. Siderophore production and utilization by marine bacteria in the North Pacific Ocean

   https://doi.org/10.1002/lno.12373  

   Park, Jiwoon; Durham, Bryndan P; Key, Rebecca S; Groussman, Ryan D; Bartolek, Zinka; Pinedo‐Gonzalez, Paulina; Hawco, Nicholas J; John, Seth G; Carlson, Michael_C G; Lindell, Debbie; et al (July 2023, Limnology and Oceanography)

   Abstract Siderophores are strong iron‐binding molecules produced and utilized by microbes to acquire the limiting nutrient iron (Fe) from their surroundings. Despite their importance as a component of the iron‐binding ligand pool in seawater, data on the distribution of siderophores and the microbes that use them are limited. Here, we measured the concentrations and types of dissolved siderophores during two cruises in April 2016 and June 2017 that transited from the iron‐replete, low‐macronutrient North Pacific Subtropical Gyre through the North Pacific Transition Zone (NPTZ) to the iron‐deplete, high‐macronutrient North Pacific Subarctic Frontal Zone (SAFZ). Surface siderophore concentrations in 2017 were higher in the NPTZ (4.0–13.9 pM) than the SAFZ (1.2–5.1 pM), which may be partly attributed to stimulated siderophore production by environmental factors such as dust‐derived iron concentrations (up to 0.51 nM). Multiple types of siderophores were identified on both cruises, including ferrioxamines, amphibactins, and iron‐free forms of photoreactive siderophores, which suggest active production and use of diverse siderophores across latitude and depth. Siderophore biosynthesis and uptake genes and transcripts were widespread across latitude, and higher abundances of these genes and transcripts at higher latitudes may reflect active siderophore‐mediated iron uptake by the local bacterial community across the North Pacific. The variability in the taxonomic composition of bacterial communities that transcribe putative ferrioxamine, amphibactin, and salmochelin transporter genes at different latitudes further suggests that the microbial groups involved in active siderophore production and usage change depending on local conditions. 

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4. Stereospecific control of microbial growth by a combinatoric suite of chiral siderophores

   https://doi.org/10.1073/pnas.2423730122  

   Stow, Parker R; Forsch, Kiefer O; Thomsen, Emil; Naka, Hiroaki; Haygood, Margo G; Barbeau, Katherine A; Butler, Alison (March 2025, Proceedings of the National Academy of Sciences)

   Bacteria compete for iron by producing small-molecule chelators known as siderophores. The triscatechol siderophores trivanchrobactin and ruckerbactin, produced byVibrio campbelliiDS40M4 andYersinia ruckeriYRB, respectively, are naturally occurring diastereomers that form chiral ferric complexes in opposing enantiomeric configurations. Chiral recognition is a hallmark of specificity in biological systems, yet the biological consequences of chiral coordination compounds are relatively unexplored. We demonstrate stereoselective discrimination of microbial growth and iron uptake by chiral Fe(III)–siderophores. The siderophore utilization pathway inV. campbelliiDS40M4 is stereoselective for Λ-Fe(III)–trivanchrobactin, but not the mismatched Δ-Fe(III)–ruckerbactin diastereomer. Chiral recognition is likely conferred by the stereospecificity of both the outer membrane receptor (OMR) protein FvtA and the periplasmic binding protein (PBP) FvtB, both of which must interact preferentially with the Λ-configured Fe(III)-coordination complexes. 

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5. The Global Regulator MftR Controls Virulence and Siderophore Production in Burkholderia thailandensis

   https://doi.org/10.1128/jb.00237-22  

   Thapa, Sudarshan S.; Al-Tohamy, Ahmed; Grove, Anne (November 2022, Journal of Bacteriology)

   Comstock, Laurie E. (Ed.)

   ABSTRACT Burkholderia thailandensis is a member of the Burkholderia pseudomallei complex. It encodes the transcription factor MftR, which is conserved among the more pathogenic Burkholderia spp. and previously shown to be a global regulator of gene expression. We report here that a B. thailandensis strain in which the mftR gene is disrupted is more virulent in both Caenorhabditis elegans and onion. The Δ mftR strain exhibits a number of phenotypes associated with virulence. It is more proficient at forming biofilm, and the arcDABC gene cluster, which has been linked to anaerobic survival and fitness within a biofilm, is upregulated. Swimming and swarming motility are also elevated in Δ mftR cells. We further show that MftR is one of several transcription factors which control production of the siderophore malleobactin. MftR binds directly to the promoter driving expression of mbaS , which encodes the extracytoplasmic function sigma factor MbaS that is required for malleobactin production. Malleobactin is a primary siderophore in B. thailandensis as evidenced by reduced siderophore production in mbaS ::Tc cells, in which mbaS is disrupted. Expression of mbaS is increased ~5-fold in Δ mftR cells, and siderophore production is elevated. Under iron-limiting conditions, mbaS expression is increased ~150-fold in both wild-type and Δ mftR cells, respectively, reflecting regulation by the ferric uptake regulator (Fur). The mbaS expression profiles also point to repression by a separate, ligand-responsive transcription factor, possibly ScmR. Taken together, these data indicate that MftR controls a number of phenotypes, all of which promote bacterial survival in a host environment. IMPORTANCE Bacterial pathogens face iron limitation in a host environment. To overcome this challenge, they produce siderophores, small iron-chelating molecules. Uptake of iron-siderophore complexes averts bacterial iron limitation. In Burkholderia spp., malleobactin or related compounds are the primary siderophores. We show here that genes encoding proteins required for malleobactin production in B. thailandensis are under the direct control of the global transcription factor MftR. Repression of gene expression by MftR is relieved when MftR binds xanthine, a purine metabolite present in host cells. Our work therefore identifies a mechanism by which siderophore production may be optimized in a host environment, thus contributing to bacterial fitness. 

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