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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. (August 2021, 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 ΔasbB::kmr, 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. 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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4. 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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5. Genomic and microbiological analyses of iron acquisition pathways among respiratory and environmental nontuberculous mycobacteria from Hawai’i

   https://doi.org/10.3389/fmicb.2023.1268963  

   Tan, Cara G.; Oberlag, Nicole M.; McGowan, Acelyn E.; Dawrs, Stephanie N.; Chan, Yvonne L.; Strong, Michael; Hasan, Nabeeh A.; Honda, Jennifer R. (November 2023, Frontiers in Microbiology)

   As environmental opportunistic pathogens, nontuberculous mycobacteria (NTM) can cause severe and difficult to treat pulmonary disease. In the United States, Hawai’i has the highest prevalence of infection. Rapid growing mycobacteria (RGM) such asMycobacterium abscessusandM. porcinumand the slow growing mycobacteria (SGM) includingM. intracellularesubspecieschimaeraare common environmental NTM species and subspecies in Hawai’i. Although iron acquisition is an essential process of many microorganisms, iron acquisition via siderophores among the NTM is not well-characterized. In this study, we apply genomic and microbiological methodologies to better understand iron acquisition via siderophores for environmental and respiratory isolates ofM. abscessus,M. porcinum, andM. intracellularesubspecieschimaerafrom Hawai’i. Siderophore synthesis and transport genes, including mycobactin(mbt), mmpL/S, andesx-3were compared among 47 reference isolates, 29 respiratory isolates, and 23 environmental Hawai’i isolates. Among all reference isolates examined, respiratory isolates showed significantly more siderophore pertinent genes compared to environmental isolates. Among the Hawai’i isolates, RGMM. abscessusandM. porcinumhad significantly lessesx-3 andmbtgenes compared to SGMM. chimaerawhen stratified by growth classification. However, no significant differences were observed between the species when grown on low iron culture agar or siderophore production by the chrome azurol S (CAS) assayin vitro. These results indicate the complex mechanisms involved in iron sequestration and siderophore activity among diverse NTM species. 

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