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1. Sulfur starvation induces an Fe-replete response and attenuates virulence pathways in Pseudomonas aeruginosa PAO1

   https://doi.org/10.1186/s12866-025-04442-1  

   Ugochukwu, Chidozie G; Schwartz, Tonia S; Zeczycki, Tonya N; Goodwin, Douglas C; Ellis, Holly R (December 2025, BMC Microbiology)

   Understanding bacterial responses to nutrient limitation is critical for developing targeted antimicrobial strategies. Sulfur starvation uniquely induces not only genes responsible for sulfur scavenging but also prominent antioxidant defenses. However, the biological rationale behind the simultaneous induction of antioxidants during sulfur limitation remains largely unexplored. Our study addresses this gap by integrating transcriptomic, proteomic, and targeted metabolomic data fromPseudomonas aeruginosaPAO1 grown under sulfur-free conditions. ResultsAs anticipated, transcripts and proteins involved in sulfur assimilation and metabolism—including members of themsu,ssu, andcysoperons—were upregulated, along with key antioxidant enzymes such as Ohr, LsfA, and SodB. Unexpectedly, however, genes encoding iron uptake systems (pyoverdine, pyochelin, and heme metabolism operons) were markedly downregulated, while iron storage proteins (BfrB, Dps, and PA4880) were elevated, indicating an iron-replete metabolic state. Further targeted metabolic profiling and iron quantification assays confirmed reduced Fe acquisition and diminished extracellular levels of siderophore and phenazine metabolites. This shift in iron homeostasis correlated with the repression of multiple virulence factors regulated by Fur and PrrF, including quorum-sensing components, efflux pumps, and phenazine biosynthesis enzymes. ConclusionOur integrative analysis reveals that sulfur starvation critically regulates iron homeostasis by linking reduced Fe uptake to the induction of antioxidant defenses. This iron-buffering response likely mitigates oxidative damage from unincorporated Fe, representing a protective metabolic adaptation. Additionally, the concurrent attenuation of virulence pathways suggests that targeting sulfur metabolism could disrupt iron-dependent virulence gene regulation, offering therapeutic insights into nutritional immunity strategies. Collectively, our findings uncover a novel sulfur-iron axis that plays a central role in oxidative stress management and pathogenicity modulation in bacteria. Graphical abstractUsing high-throughput RNA-sequencing and proteomics techniques, we identified genes and metabolites differentially expressed during sulfur starvation inP. aeruginosagrown in minimal media. Additional experiments using a range of biophysical techniques were used to quantify select metabolites and Fe. Overall, we found that sulfur starvation induced an Fe-replete response, characterized by the repression of Fe uptake pathways and the upregulation of Fe storage genes. 

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2. Transcriptional Responses to Priority Effects in Nectar Yeast

   https://doi.org/10.1111/mec.17553  

   Chappell, Callie R; Goddard, Pagé C; Golden, Lexi‐Ann; Hernandez, Jonathan; Ortiz Chavez, Daniela; Hossine, Marziiah; Herrera Paredes, Sur; VanValkenburg, Ethan; Nell, Lucas A; Fukami, Tadashi; et al (October 2024, Molecular Ecology)

   Priority effects, where the order and timing of species arrival influence the assembly of ecological communities, have been observed in a variety of taxa and habitats. However, the genetic and molecular basis of priority effects remains unclear, hindering a better understanding of when priority effects will be strong. We sought to gain such an understanding for the nectar yeastMetschnikowia reukaufiicommonly found in the nectar of our study plant, the hummingbird‐pollinatedDiplacus(Mimulus)aurantiacus. In this plant,M.reukaufiican experience strong priority effects when it reaches flowers after other nectar yeasts, such asM.rancensis. After inoculation into two contrasting types of synthetic nectar simulating early arrival ofM.rancensis, we conducted whole‐transcriptome sequencing of 108 strains ofM.reukaufii. We found that several genes were differentially expressed inM.reukaufiistrains when the nectar had been conditioned by growth ofM.rancensis. Many of these genes were associated with amino acid metabolism, suggesting thatM.reukaufiistrains responded molecularly to the reduction in amino acid availability caused byM.rancensis. Furthermore, investigation of expression quantitative trait loci (eQTLs) revealed that genes involved in amino acid transport and resistance to antifungal compounds were enriched in some genetic variants ofM.reukaufii. We also found that gene expression was associated with population growth rate, particularly when amino acids were limited. These results suggest that intraspecific genetic variation in the ability of nectar yeasts to respond to nutrient limitation and direct fungal competition underpins priority effects in this microbial system. 

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3. Mixtures of phthalates disrupt expression of genes related to lipid metabolism and peroxisome proliferator-activated receptor signaling in mouse granulosa cells

   Hanin, Alahmadi; Stephanie, Martinez; Rivka, Farrell; Rafiatou, Bikienga; Nneka, Arinzeh; Courtney, Potts; Zhong, Li; Genoa, Warner (August 2024, Current research in toxicology)

   Jeffrey, Peters; Alison, Harrill; Kristine, Willett (Ed.)

   Phthalates are a class of known endocrine-disrupting chemicals that are found in common everyday products. Several studies associate phthalate exposure with detrimental effects on ovarian function, including growth and development of the follicle and production of steroid hormones. We hypothesized that dysregulation of the ovary by phthalates may be mediated by phthalate toxicity towards granulosa cells, a major cell type in ovarian follicles responsible for key steps of hormone production and nourishing the developing oocyte. To test the hypothesis that phthalates target granulosa cells, we harvested granulosa cells from adult CD-1 mouse ovaries and cultured them for 96 h in vehicle control, a phthalate mixture, or a phthalate metabolite mixture (0.1 to 100 μg/ml). After culture, we measured metabolism of the phthalate mixture into monoester metabolites by the granulosa cells, finding that granulosa cells do not significantly contribute to ovarian metabolism of phthalates. Immunohistochemistry of phthalate metabolizing enzymes in whole ovaries confirmed that these enzymes are not strongly expressed in granulosa cells of antral follicles and that ovarian metabolism of phthalates likely occurs primarily in the stroma. RNA sequencing of treated granulosa cells identified 407 differentially expressed genes, with overrepresentation of genes from lipid metabolic processes, cholesterol metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Expression of significantly differentially expressed genes related to these pathways was confirmed using qPCR. Our results agree with previous findings that phthalates and phthalate metabolites have different effects on the ovary, but both interfere with PPAR signaling in granulosa cells. 

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4. Validating the Cyc2 Neutrophilic Iron Oxidation Pathway Using Meta-omics of Zetaproteobacteria Iron Mats at Marine Hydrothermal Vents

   https://doi.org/10.1128/mSystems.00553-19  

   McAllister, Sean M.; Polson, Shawn W.; Butterfield, David A.; Glazer, Brian T.; Sylvan, Jason B.; Chan, Clara S.; Lloyd, Karen G. (February 2020, mSystems)

   ABSTRACT Zetaproteobacteria create extensive iron (Fe) oxide mats at marine hydrothermal vents, making them an ideal model for microbial Fe oxidation at circumneutral pH. Comparison of neutrophilic Fe oxidizer isolate genomes has revealed a hypothetical Fe oxidation pathway, featuring a homolog of the Fe oxidase Cyc2 from Acidithiobacillus ferrooxidans . However, Cyc2 function is not well verified in neutrophilic Fe oxidizers, particularly in Fe-oxidizing environments. Toward this, we analyzed genomes and metatranscriptomes of Zetaproteobacteria , using 53 new high-quality metagenome-assembled genomes reconstructed from Fe mats at Mid-Atlantic Ridge, Mariana Backarc, and Loihi Seamount (Hawaii) hydrothermal vents. Phylogenetic analysis demonstrated conservation of Cyc2 sequences among most neutrophilic Fe oxidizers, suggesting a common function. We confirmed the widespread distribution of cyc2 and other model Fe oxidation pathway genes across all represented Zetaproteobacteria lineages. High expression of these genes was observed in diverse Zetaproteobacteria under multiple environmental conditions and in incubations. The putative Fe oxidase gene cyc2 was highly expressed in situ , often as the top expressed gene. The cyc2 gene showed increased expression in Fe(II)-amended incubations, with corresponding increases in carbon fixation and central metabolism gene expression. These results substantiate the Cyc2-based Fe oxidation pathway in neutrophiles and demonstrate its significance in marine Fe-mineralizing environments. IMPORTANCE Iron oxides are important components of our soil, water supplies, and ecosystems, as they sequester nutrients, carbon, and metals. Microorganisms can form iron oxides, but it is unclear whether this is a significant mechanism in the environment. Unlike other major microbial energy metabolisms, there is no marker gene for iron oxidation, hindering our ability to track these microbes. Here, we investigate a promising possible iron oxidation gene, cyc2 , in iron-rich hydrothermal vents, where iron-oxidizing microbes dominate. We pieced together diverse Zetaproteobacteria genomes, compared these genomes, and analyzed expression of cyc2 and other hypothetical iron oxidation genes. We show that cyc2 is widespread among iron oxidizers and is highly expressed and potentially regulated, making it a good marker for the capacity for iron oxidation and potentially a marker for activity. These findings will help us understand and potentially quantify the impacts of neutrophilic iron oxidizers in a wide variety of marine and terrestrial environments. 

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5. Characterizing host-pathogen interactions between Zostera marina and Labyrinthula zosterae

   https://doi.org/10.3389/fmars.2023.1152647  

   Venkataraman, Yaamini R; Shore, Amanda; Dayal, Sukanya; Lee, James Sanghyun; Alidoost_Salimi, Mahsa; Crandall, Grace; Loeher, Malina M; Stoops, Mark; Swanger, Megan; Eisenlord, Morgan E; et al (August 2023, Frontiers in Marine Science)

   IntroductionSeagrass meadows serve as an integral component of coastal ecosystems but are declining rapidly due to numerous anthropogenic stressors including climate change. Eelgrass wasting disease, caused by opportunisticLabyrinthulaspp., is an increasing concern with rising seawater temperature. To better understand the host-pathogen interaction, we paired whole organism physiological assays with dual transcriptomic analysis of the infected host and parasite. MethodsEelgrass (Zostera marina) shoots were placed in one of two temperature treatments, 11° C or 18° C, acclimated for 10 days, and exposed to a waterborne inoculation containing infectiousLabyrinthula zosterae(Lz) or sterile seawater. At two- and five-days post-exposure, pathogen load, visible disease signs, whole leaf phenolic content, and both host- and pathogen- transcriptomes were characterized. ResultsTwo days after exposure, more than 90% of plants had visible lesions andLzDNA was detectable in 100% percent of sampled plants in theLzexposed treatment. Concentrations of total phenolic compounds were lower after 5 days of combined exposure to warmer temperatures andLz, but were unaffected in other treatments. Concentrations of condensed tannins were not affected byLzor temperature, and did not change over time. Analysis of the eelgrass transcriptome revealed 540 differentially expressed genes in response toLzexposure, but not temperature.Lz-exposed plants had gene expression patterns consistent with increased defense responses through altered regulation of phytohormone biosynthesis, stress response, and immune function pathways. Analysis of the pathogen transcriptome revealed up-regulation of genes potentially involved in breakdown of host defense, chemotaxis, phagocytosis, and metabolism. DiscussionThe lack of a significant temperature signal was unexpected but suggests a more pronounced physiological response toLzinfection as compared to temperature. Pre-acclimation of eelgrass plants to the temperature treatments may have contributed to the limited physiological responses to temperature. Collectively, these data characterize a widespread physiological response to pathogen attack and demonstrate the value of paired transcriptomics to understand infections in a host-pathogen system. 

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