Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an A5cla cluster from Penicillium sp. MYA5, derived from the Arctic plant Dryas octopetala, is responsible for clavatol biosynthesis. Seven clavatols, including one new clavatol derivate named penicophenone F (1) and six known clavatols (2-7), were isolated from Penicillium sp. MYA5 using a transcriptome mining strategy. These structures were elucidated by comprehensive spectroscopic analysis. Antibacterial, aldose reductase inhibition, and siderophore-producing ability assays were conducted on compounds 1-7. Compounds 1 and 2 demonstrated inhibitory effects on the ALR2 enzyme with inhibition rates of 75.3% and 71.6% at a concentration of 10 μM, respectively. Compound 6 exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 4.0 μg/mL and 4.0 μg/mL, respectively. Additionally, compounds 1, 5, and 6 also showed potential iron-binding ability.

BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness.
METHODS: Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy.
RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness.
CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.

The pyoverdine siderophore is produced by Pseudomonas aeruginosa to access iron. Its synthesis involves the complex coordination of four nonribosomal peptide synthetases (NRPSs), which are responsible for assembling the pyoverdine peptide backbone. The precise cellular organization of these NRPSs and their mechanisms of interaction remain unclear. Here, we used a combination of several single-molecule microscopy techniques to elucidate the spatial arrangement of NRPSs within pyoverdine-producing cells. Our findings reveal that PvdL differs from the three other NRPSs in terms of localization and mobility patterns. PvdL is predominantly located in the inner membrane, while the others also explore the cytoplasmic compartment. Leveraging the power of multicolor single-molecule localization, we further reveal co-localization between PvdL and the other NRPSs, suggesting a pivotal role for PvdL in orchestrating the intricate biosynthetic pathway. Our observations strongly indicates that PvdL serves as a central orchestrator in the assembly of NRPSs involved in pyoverdine biosynthesis, assuming a critical regulatory function.

Bacillus species appearas the most attractive plant growth-promoting rhizobacteria (PGPR) and alternative to synthetic chemical pesticides. The present study examined the antagonistic potential of spore forming-Bacilli isolated from organic farm soil samples of Allahabad, India. Eighty-seven Bacillus strains were isolated and characterized based on their morphological, plant growth promoting traits and molecular characteristics. The diversity analysis used 16S-rDNA, BOX-element, and enterobacterial repetitive intergenic consensus. Two strains, PR30 and PR32, later identified as Bacillus sp., exhibited potent in vitro antagonistic activity against Ralstonia solanaceorum. These isolates produced copious amounts of multiple PGP traits, such as indole-3-acetic acid (40.0 and 54.5 μg/mL), phosphate solubilization index (PSI) (4.4 and 5.3), ammonia, siderophore (3 and 4 cm), and 1-aminocyclopropane-1-carboxylate deaminase (8.1and 9.2 μM/mg//h) and hydrogen cyanide. These isolates were subjected to the antibiotic sensitivity test. The two potent isolates based on the higher antagonistic and the best plant growth-promoting ability were selected for plant growth-promoting response studies in tomatoe, broccoli, and chickpea. In the pot study, Bacillus subtilis (PR30 and PR31) showed significant improvement in seed germination (27-34%), root length (20-50%), shoot length (20-40%), vigor index (50-75%), carotenoid content (0.543-1.733), and lycopene content (2.333-2.646 mg/100 g) in tomato, broccoli, and chickpea. The present study demonstrated the production of multiple plant growth-promoting traits by the isolates and their potential as effective bioinoculants for plant growth promotion and biocontrol of phytopathogens.

BACKGROUND: Carbapenem-resistant E. coli (CREco) pose a significant public health threat due to their multidrug resistance. Colistin is often a last-resort treatment against CREco; however, the emergence of colistin resistance gene mcr-1 complicates treatment options.
METHODS: Two E. coli strains (ECO20 and ECO21), recovered from hospitalized patients in distinct wards, exhibited resistance to carbapenems and colistin. Whole-genome sequencing and phenotypic characterization were employed to study resistance patterns, plasmid profiles, transferability of resistance and virulence genes, and siderophore production capabilities. Comparative genome analysis was used to investigate the genetic environment of mcr-1, blaNDM-7, and virulence clusters.
RESULTS: Both E. coli strains exhibited thr presence of both mcr-1 and blaNDM-7 genes, showing high resistance to multiple antibiotics. Genomic analysis revealed the clonal transmission of these strains, possessing identical plasmid profiles (pMCR, pNDM, and pVir) associated with colistin resistance, carbapenem resistance, and virulence factors. Conjugation experiments confirmed the transferability of these plasmids, indicating their potential to disseminate resistance and virulence traits to other strains. Comparative genomic analyses unveiled the distribution of mcr-1 (IncX4-type) and blaNDM (IncX3-type) plasmids across diverse bacterial species, emphasizing their adaptability and threat. The novelty of pVir indicates its potential role in driving the evolution of highly adaptable and pathogenic strains.
CONCLUSIONS: Our findings underscore the co-occurrence of mcr-1, blaNDM-7, and siderophore-producing plasmids in E. coli, which poses a significant concern for global health. This research is crucial to unravel the complex mechanisms governing plasmid transfer and recombination and to devise robust strategies to control their spread in healthcare settings.

Ferroptosis is an iron-dependent cell death that was discovered recently. For beneficial microbes to establish mutualistic relationships with hosts, precisely controlled cell death in plant cells is necessary. However, whether ferroptosis is involved in the endophyte‒plant system is poorly understood. Here, we reported that endophytic Streptomyces hygroscopicus OsiSh-2, which established a sophisticated and beneficial interaction with host rice plants, caused ferroptotic cell death in rice characterized by ferroptosis- and immune-related markers. Treatments with ferroptosis inhibitors and inducers, different doses of OsiSh-2, and the siderophore synthesis-deficient mutant ΔcchH revealed that only moderate ferroptosis induced by endophytes is essential for the establishment of an optimal symbiont to enhance plant growth. Additionally, ferroptosis involved in a defence-primed state in rice, which contributed to improved resistance against rice blast disease. Overall, our study provides new insights into the mechanisms of endophyte‒plant interactions mediated by ferroptosis and suggests new directions for crop yield promotion.

The gastrointestinal tract is densely colonized by a polymicrobial community known as the microbiota which serves as primary line of defence against pathogen invasion. The microbiota can limit gut-luminal pathogen growth at different stages of infection. This can be traced to specific commensal strains exhibiting direct or indirect protective functions. Although these mechanisms hold the potential to develop new approaches to combat enteric pathogens, they remain far from being completely described. In this study, we investigated how a mouse commensal Escherichia coli can outcompete Salmonella enterica serovar Typhimurium (S. Tm). Using a salmonellosis mouse model, we found that the commensal E. coli 8178 strain relies on a trojan horse trap strategy to limit S. Tm expansion in the inflamed gut. Combining mutants and reporter tools, we demonstrated that inflammation triggers the expression of the E. coli 8178 antimicrobial microcin H47 toxin which, when fused to salmochelin siderophores, can specifically alter S. Tm growth. This protective function was compromised upon disruption of the E. coli 8178 tonB-dependent catecholate siderophore uptake system, highlighting a previously unappreciated crosstalk between iron intake and microcin H47 activity. By identifying the genetic determinants mediating S. Tm competition, our work not only provides a better mechanistic understanding of the protective function displayed by members of the gut microbiota but also further expands the general contribution of microcins in bacterial antagonistic relationships. Ultimately, such insights can open new avenues for developing microbiota-based approaches to better control intestinal infections.

There is an urgent need for new bioactive molecules with unique mechanisms of action and chemistry to address the issue of incorrect use of chemical fertilizers and pesticides, which hurts both the environment and the health of humans. In light of this, research was done for this work to isolate, identify, and evaluate the germination-promoting potential of various plant species\' fungal endophytes. Zea mays L. (maize) seed germination was examined using spore suspension of 75 different endophytic strains that were identified. Three promising strains were identified through screening to possess the ability mentioned above. These strains Alternaria alternate, Aspergilus flavus, and Aspergillus terreus were isolated from the stem of Tecoma stans, Delonix regia, and Ricinus communis, respectively. The ability of the three endophytic fungal strains to produce siderophore and indole acetic acid (IAA) was also examined. Compared to both Aspergillus flavus as well as Aspergillus terreus, Alternaria alternata recorded the greatest rates of IAA, according to the data that was gathered. On CAS agar versus blue media, all three strains failed to produce siderophores. Moreover, the antioxidant and antifungal potentials of extracts from these fungi were tested against different plant pathogens. The obtained results indicated the antioxidant and antifungal activities of the three fungal strains. GC-Mass studies were carried out to determine the principal components in extracts of all three strains of fungi. The three strains\' fungus extracts included both well-known and previously unidentified bioactive compounds. These results may aid in the development of novel plant growth promoters by suggesting three different fungal strains as sources of compounds that may improve seed germination. According to the study that has been given, as unexplored sources of bioactive compounds, fungal endophytes have great potential.

Biofilms commonly develop in immunocompromised patients, which leads to persistent infections that are difficult to treat. In the biofilm state, bacteria are protected against both antibiotics and the host\'s immune system; currently, there are no therapeutics that target biofilms. In this study, we screened a chemical fraction library representing the natural product capacity of the microbiota of marine egg masses, namely, the moon snail egg collars. This led to the identification of active fractions targeting both Pseudomonas aeruginosa and Staphylococcus aureus biofilms. Subsequent analysis revealed that a subset of these fractions were capable of eradicating preformed biofilms, all against S. aureus. Bioassay-guided isolation led us to identify pseudochelin A, a known siderophore, as a S. aureus biofilm inhibitor with an IC50 of 88.5 μM. Mass spectrometry-based metabolomic analyses revealed widespread production of pseudochelin A among fractions possessing S. aureus antibiofilm properties. In addition, a key biosynthetic gene involved in producing pseudochelin A was detected on 30% of the moon snail egg collars and pseudochelin A is capable of inhibiting the formation of biofilms (IC50 50.6 μM) produced by ecologically relevant bacterial strains. We propose that pseudochelin A may have a role in shaping the microbiome or protecting the egg collars from microbiofouling.

Phytopathogenic Fusarium graminearum poses significant threats to crop health and soil quality. Although our laboratory-cultivated Pseudomonas sp. P13 exhibited potential biocontrol capacities, its effectiveness against F. graminearum and underlying antifungal mechanisms are still unclear. In light of this, our study investigated a significant inhibitory effect of P13 on F. graminearum T1, both in vitro and in a soil environment. Conducting genomic, metabolomic, and transcriptomic analyses of P13, we sought to identify evidence supporting its antagonistic effects on T1. The results revealed the potential of P13, a novel Pseudomonas species, to produce active antifungal components, including phenazine-1-carboxylate (PCA), hydrogen cyanide (HCN), and siderophores [pyoverdine (Pvd) and histicorrugatin (Hcs)], as well as the dynamic adaptive changes in the metabolic pathways of P13 related to these active ingredients. During the logarithmic growth stage, T1-exposed P13 strategically upregulated PCA and HCN biosynthesis, along with transient inhibition of the tricarboxylic acid (TCA) cycle. However, with growth stabilization, upregulation of PCA and HCN synthesis ceased, whereas the TCA cycle was enhanced, increasing siderophores secretion (Pvd and Hcs), suggesting that this mechanism might have caused continuous inhibition of T1. These findings improved our comprehension of the biocontrol mechanisms of P13 and provided the foundation for potential application of Pseudomonas strains in the biocontrol of phytopathogenic F. graminearum.
OBJECTIVE: Pseudomonas spp. produces various antifungal substances, making it an effective natural biocontrol agent against pathogenic fungi. However, the inhibitory effects and the associated antagonistic mechanisms of Pseudomonas spp. against Fusarium spp. are unclear. Multi-omics integration analyses of the in vitro antifungal effects of novel Pseudomonas species, P13, against F. graminearum T1 revealed the ability of P13 to produce antifungal components (PCA, HCN, Pvd, and Hcs), strategically upregulate PCA and HCN biosynthesis during logarithmic growth phase, and enhance the TCA cycle during stationary growth phase. These findings improved our understanding of the biocontrol mechanisms of P13 and its potential application against pathogenic fungi.