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Prodigiosin, a valuable intracellular secondary metabolite, is produced by Serratia marcescens. However, synthesis during fermentation is constrained by osmotic pressure. In this study, adaptive laboratory evolution was applied to the strain SDSPY-136 to improve osmotic stress tolerance. After 120 passages, screening and validation yielded a strain with high osmotic pressure resistance, S. marcescens R82. The UV absorption spectrum, HPLC peak time, FTIR functional groups, and 1H NMR chemical shifts revealed that the pigment generated by the evolved strain was prodigiosin. After batch fermentation in a 5 L bioreactor, the prodigiosin concentration was 11.4 g/L, double the initial strain. Transcriptomic analyses revealed significant enrichment for 830 genes. R82 showed alterations in various pathways, indicating that the regulation of intracellular metabolic pathways promoted the availability of prodigiosin precursors, increasing the capacity for prodigiosin synthesis and extracellular release. This study clarifies the molecular evolution mechanism and presents a novel approach for improving yields in S. marcescens. [Display omitted] • Serratia marcescens was modified through adaptive laboratory evolution. • Pigment of the evolved R82 strain was characterized using spectroscopy. • Strain R82 was tolerant to osmotic pressure. • Batch fermentation yielded 11.4 g/L prodigiosin in 5 L bioreactors. • Transcriptome sequencing was used to analyze the evolutionary mechanism. [ABSTRACT FROM AUTHOR]

Cheese is a biologically active food product, characterised by its colour, texture, and taste. Due to its rich matrix of fats and proteins, as well as the fact that the cheese's surface acts as its own packaging, the cheese becomes more susceptible to contamination by microorganisms during the ripening process, particularly bacteria and fungi. The ripening of cheese involves several biochemical reactions, with the proteolytic activity of the cheese microbiota being particularly significant. Proteolysis results in the presence of free amino acids, which are precursors to various metabolic mechanisms that can cause discolouration (blue, pink, and brown) on the cheese rind. Surface defects in cheese have been documented in the literature for many years. Sporadic inconsistencies in cheese appearance can lead to product degradation and economic losses for producers. Over the past few decades, various defects have been reported in different types of cheese worldwide. This issue also presents opportunities for innovation and development in edible and bioactive coatings to prevent the appearance of colour defects. Therefore, this review provides a comprehensive analysis of cheese colour globally, identifying defects caused by microorganisms. It also explores strategies and innovation opportunities in the cheese industry to enhance the value of the final product. [ABSTRACT FROM AUTHOR]

Prodigiosin is a fascinating compound that has been gaining attention in the scientific community for its diverse range of potential applications. From its vibrant red color to its unique chemical properties, prodigiosin has captured the interest of researchers looking for innovative solutions in various fields. Prodigiosin, a red pigment produced by certain bacteria such as Serratia marcescens, has attracted interest from pharmaceutical researchers due to its promising potential in various therapeutic applications. A number of studies have demonstrated the potential of prodigiosin as an antimicrobial agent. With the rise of antibiotic resistance in the environment, prodigiosin is a promising solution to combat resistant strains and improve the effectiveness of existing antibiotic therapy. Moreover, different studies have shown that this natural pigment has anticancer properties by inhibiting the growth and proliferation of cancer cells. Prodigiosin exerts its anticancer effects by inducing apoptosis in cancer cells without causing significant damage to healthy cells. In this review, we will attempt to summarize the capabilities of prodigiosin and its prospects as a valuable tool in pharmaceutical research, and also review recent studies focusing on the various industries in which prodigiosin can be applied and the exciting possibilities it holds in the future. [ABSTRACT FROM AUTHOR]

Dengue (DENV) and Zika virus (ZIKV), transmitted by Aedes mosquitoes, pose significant public health challenges. Effective treatments for these viruses remain elusive, highlighting the urgent need for new efficient antiviral therapies. This study explores prodigiosin, a microbial tripyrrole pigment, as an antiviral agent against both DENV and ZIKV employing advanced analytical approaches which integrate molecular docking, CASTp 3.0 validation and molecular dynamics (MD) simulations providing insights into molecular interactions at an atomic level. Prodigiosin exhibited favourable drug‐likeness properties, meeting Lipinski's rule of five and demonstrating optimal physicochemical and pharmacokinetic characteristics according to Ghose's, Veber's, Egan's and Muegge's filters, essential for oral bioavailability. Absorption, Distribution, Metabolism, Excretion, and Toxicity profiling indicated high intestinal absorption, minimal risk for drug‐drug interactions and a low toxicity profile, with no AMES toxicity, hepatotoxicity, or skin sensitization. Molecular docking revealed prodigiosin's strong binding affinities to NS5 methyltransferases of both DENV (−7.6 kcal/mol) and ZIKV (−7.7 kcal/mol) viruses, suggesting potential disruption of viral replication. Notably, prodigiosin's binding affinities were comparable to ribavirin‐5'‐triphosphate and chloroquine, known inhibitors of DENV and ZIKV, respectively. MD simulations confirmed stable and specific interactions with prodigiosin with low root‐mean‐square deviation values. Additional analyses, including root‐mean‐square fluctuation, radius of gyration and solvent‐accessible surface area, indicated compact and stable complexes. These multi‐parametric in‐silico analytical strategies provide a novel perspective of prodigiosin as an antiviral agent, demonstrating its drug interactions at the molecular level. These promising results suggest that prodigiosin could serve as a broad‐spectrum antiviral agent against both DENV and ZIKV, warranting further experimental validation for therapeutic development against flaviviral infections. [ABSTRACT FROM AUTHOR]

Prodigiosin finds tremendous application in the food industry owing to its physicochemical and non-toxic attributes. In the present investigation, microbial production of food color (prodigiosin) was done by Serratia marcescens NCIM 5246 under solid-state fermentation (SSF). For economical prodigiosin yield, initial substrate screening was conducted using agro-waste such as rice bran, wheat bran, orange peel powder, green gram husk and cane molasses. A maximum pigment yield of 1059.67 ± 1.53 µg/L was observed on wheat bran media. Further, Taguchi Design of the experiment (DOE) using Qualitek-4 software with bigger is better as quality attributes was done for process optimization. The Taguchi (DOE) comprised five independent variables, i.e., pH, temperature, substrate concentration, trace metal concentration, and inoculum size at two levels. The software deduced independent variables' individual and interactive effects on product yield by performing an L8 orthogonal array (OA). The output variable (prodigiosin yield) was improved based on the S/N ratio. Under optimized cultural conditions maximum prodigiosin yield of 1320.2 ± 20 µg/L was obtained. The expected prodigiosin yield of 1386.60 µg/L showed a 95% resemblance with the actual yield, showed model validation, and 24.57% improvement in overall yield. The extracted pigment was purified by TLC and was characterized as prodigiosin by absorption spectroscopy and FTIR. [ABSTRACT FROM AUTHOR]

Copyright of Food & Fermentation Industries is the property of Food & Fermentation Industries and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Prodigiosin is a red bacterial pigment with great potential as a natural dye and drug precursor, while presenting several pharmacological properties, including antimicrobial and anticancer activities. Its commercialization for biomedical applications, however, remains scarce. The major limitations are related to the lack of efficient bioprocesses and scaling up from laboratory to production. In the present work, the upstream process for prodigiosin production was developed using a marine Serratia rubidaea isolated from a sample collected near a shallow-water hydrothermal vent. The yield of product per biomass was found to be influenced by the cell concentration in the inoculum. The system was scaled up to 2 L stirred tank reactors with two different vessel geometries. It was shown that the vessel geometry and a cascade control mode for regulating the dissolved oxygen concentration influenced the volumetric oxygen mass transfer coefficient (kLa) and thus prodigiosin production. To improve product yields, strategies to mimic the aeration conditions found at the sampling site were tested. When the inoculum was grown for 5 h at 200 rpm and for 19 h at 25 rpm, which significantly decreased the oxygen available, the cells produced 588.2 mgproduct/gbiomass, corresponding to a production of 1066.2 mg of prodigiosin in 24 h and a productivity of 36.1 mgproduct/(L.h). This is a 3.7-fold increase in prodigiosin yield and a 4.5-fold increase in productivity in relation to when no particular strategy was promoted. Additionally, it was shown that lipid analysis and flow cytometry may be used as reliable at-line analytical tools, allowing the monitoring of cell condition and prodigiosin production during fermentation. [ABSTRACT FROM AUTHOR]

The negative environmental and social impacts of food waste accumulation can be mitigated by utilizing bio-refineries' approach where food waste is revalorized into high-value products, such as prodigiosin (PG), using microbial bioprocesses. The diverse biological activities of PG position it as a promising compound, but its high production cost and promiscuous bioactivity hinder its wide application. Metal ions can modulate the electronic properties of organic molecules, leading to novel mechanisms of action and increased target potency, while metal complex formation can improve the stability, solubility and bioavailability of the parent compound. The objectives of this study were optimizing PG production through bacterial fermentation using food waste, allowing good quantities of the pure natural product for further synthesizing and evaluating copper(II) and zinc(II) complexes with it. Their antimicrobial and anticancer activities were assessed, and their binding affinity toward biologically important molecules, bovine serum albumin (BSA) and DNA was investigated by fluorescence emission spectroscopy and molecular docking. The yield of 83.1 mg/L of pure PG was obtained when processed meat waste at 18 g/L was utilized as the sole fermentation substrate. The obtained complexes CuPG and ZnPG showed high binding affinity towards target site III of BSA, and molecular docking simulations highlighted the affinity of the compounds for DNA minor grooves. [ABSTRACT FROM AUTHOR]

Wound infections caused by Multidrug-resistant Staphylococcus aureus (MRSA) have been regarded as a challenging problem in clinic for the long time. In this study, based on the excellent antimicrobial effect of prodigiosin(PG) and the ability of hydrogel dressing in terms of tissue repair and regeneration, we prepared the PG hydrogel as a treatment for the wound infection induced by MRSA. Rheological tests indicated that PG hydrogel as a semi-solid gel had good mechanical properties. In ex vitro drug permeation studies and dermatokinetic studies showed that PG hydrogel had high PG permeability and were capable of short-term retention in the skin. In addition, in vivo experiments for mouse skin wounds showed that the serum levels of inflammatory factors including IL-β and other inflammatory factors were reduced, the inflammatory infiltration of tissues was reduced, the transcript levels of genes such as COL1A1 were up-regulated at different stages of wound healing, and the relative abundance of genera such as Desulfovibrio was lowered after treatment with PG hydrogel, which facilitated wound healing in mice. Our study would provide a new solution to the clinical shortage of drugs for the treatment of MRSA infection and provide a research basis for improving the comprehensive values of PG.

Serratia marcescens is an opportunistic human pathogen that produces a vibrant red pigment called prodigiosin. Prodigiosin has implications in virulence of S. marcescens and promising clinical applications. We discovered that addition of the virulent flagellotropic bacteriophage χ (Chi) to a culture of S. marcescens stimulates a greater than fivefold overproduction of prodigiosin. Active phage infection is required for the effect, as a χ-resistant strain lacking flagella does not respond to phage presence. Via a reporter fusion assay, we have determined that the addition of a χ-induced S. marcescens cell lysate to an uninfected culture causes a threefold increase in transcription of the pig operon, containing genes essential for pigment biosynthesis. Replacement of the pig promoter with a constitutive promoter abolished the pigmentation increase, indicating that regulatory elements present in the pig promoter likely mediate the phenomenon. We hypothesize that S. marcescens detects the threat of phage-mediated cell death and reacts by producing prodigiosin as a stress response. Our findings are of clinical significance for two main reasons: (i) elucidating complex phage-host interactions is crucial for development of therapeutic phage treatments, and (ii) overproduction of prodigiosin in response to phage could be exploited for its biosynthesis and use as a pharmaceutical. [ABSTRACT FROM AUTHOR]

Serratia sp. ATCC 39006 is an important model strain for the study of prodigiosin production, whose prodigiosin biosynthesis genes (pigA-O) are arranged in an operon. Several transcription factors have been shown to control the transcription of the pig operon. However, since the regulation of prodigiosin biosynthesis is complex, the regulatory mechanism for this process has not been well established. In most γ-proteobacteria, the ROK family regulator NagC acts as a global transcription factor in response to N-acetylglucosamine (GlcNAc). In Serratia sp. ATCC 39006, NagC represses the transcription of two divergent operons, nagE and nagBAC, which encode proteins involved in the transport and metabolism of GlcNAc. Moreover, NagC directly binds to a 21-nt region that partially overlaps the -10 and -35 regions of the pig promoter and promotes the transcription of prodigiosin biosynthesis genes, thereby increasing prodigiosin production. Although NagC still acts as both repressor and activator in Serratia sp. ATCC 39006, its transcriptional regulatory activity is independent of GlcNAc. NagC was first found to regulate antibiotic biosynthesis in Gram-negative bacteria, and NagC-mediated regulation is not responsive to GlcNAc, which contributes to future studies on the regulation of secondary metabolism by NagC in other bacteria. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Guangdong Pharmaceutical University is the property of Journal of Guangdong Pharmaceutical University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Prodigiosin (PG) is a red tripyrrole pigment from the prodiginine family that has attracted widespread attention due to its excellent biological activities, including anticancer, antibacterial and anti-algal activities. The synthesis and production of PG is of particular significance, as it has the potential to be utilized in a number of applications, including those pertaining to clinical drug development, food safety, and environmental management. This paper provides a systematic review of recent research on PG, covering aspects like chemical structure, bioactivity, biosynthesis, gene composition and regulation, and optimization of production conditions, with a particular focus on the biosynthesis and regulation of PG in Serratia marcescens. This provides a solid theoretical basis for the drug development and production of PG, and is expected to promote the further development of PG in medicine and other applications. [ABSTRACT FROM AUTHOR]

In this study, Chitosan (CS) was newly found as an effective carrier for micro-encapsulation of Pg by spray drying technique for enhancing its bioactivity. Among various tested polymers, CS was screened as the most suitable substance for creating encapsulated Pg/CS microparticles (E-Pg/CS-MPs) with high recovery yield and good nanoscale properties. CS was further combined with other carbohydrate polymers and used for micro-encapsulation of Pg, however, no enhancing yield or better properties of encapsulated Pg microparticles were found. Further experiments indicated that the size of the spaying needle of 5.5 μm and the Pg concentration used at 0.05% were the most effective for producing E-Pg/CS-MPs. In nanoscale properties characterization, the E-Pg/CS-MPs were found spherical with smooth surfaces, good stability (Zeta potential of + 80.1 mV), and average sizes at 529.5 nm. Especially, the E-Pg/CS-MPs demonstrated a potent nematicidal effect against both J2-nematodes and their egg-hatching, besides, the activity of E-Pg/CS-MPs was improved by about fourfold compared with pure Pg. The molecular docking and enzyme inhibition assays suggested the possible pathway of the nematicidal effect of Pg released from E-Pg/CS-MPs via inhibition of acetylcholinesterase. This study thus provides a novel and effective protocol to produce E-Pg/CS-MPs with potential use for managing black pepper nematodes. [ABSTRACT FROM AUTHOR]

The present work aims to biosynthesis of manganese oxide nanoparticles (MnO NPs) using Prodigiosin pigment, produced by Serratia marcescens, as a stabilizing and reducing agent. In addition to the characterizing of the biosynthesized MnO NPs were characterized utilizing several optical methods, including FT-IR, XRD, AFM and UV-Vis. A cut-off wavelength of the biologically synthesized MnO NPs was established at around 440 nm using UV-Vis. Furthermore, the analysis of AFM revealed that MnO NPs have an average diameter size of 74.51 nm. The results showed concentration-dependent antibacterial effect (25, 50, 100 and 200 mg/ml) of MnO nanoparticles on Pseudomonas aeruginosa. Overall, it is concluded that the biosynthesized MnO NPs retain the potential to serve as an alternative antibacterial agents. [ABSTRACT FROM AUTHOR]

A pigment is a naturally occurring colored substance that is created by plants, animals, and microbes. Pigments are utilized in a variety of industries, including food coloring, pharmaceuticals, fabric dying, cosmetics, ink plastics, coloring paints, and so on. The Natural pigments /Bio pigments are very expensive because mass production is difficult. There are more pigments in nature, but only a small number are available in large enough amounts to be useful for industry. This study is attempted to isolate a bacterial red pigmented organism from facial acne was identified as Serratia marcescens MBM‐17 according to Bergey's manual of determinative bacteriology and molecular characterization and production of red pigment was optimized at various growth factors, maximum pigment production was at pH 4, 72 h and 37 ± 2°C, that is, 15.56 g/ L. The partial purified pigment was characterized by UV–Vis, and maximum absorbance was at 533.5 nm. SEM analysis shows that the surface morphology and FTIR spectroscopy revealed the presence of prodigiosin. Prodigiosin has antibacterial efficacy against gram positive bacterial strains, Staphylococcus aureus, Bacillus sp, and gram negative bacterial strains. Klebsiella sp, Pseudomonas sp, Salmonella sp, antifungal potency against Aspergillus niger, Aspergillus flavus, Penicillium sp, Rhizopus sp, and Mucor sp, and checked the fabric dying effects of pigments. Prodigiosin used as fabric dye is applied on clothes, which shows good color tone. This study is highlighting the production of a natural pigment/drug, Prodigiosin with antimicrobial activity may be used for the manufacture of dyed dress materials and masks having antimicrobial action for public especially health workers in this pandemic situation. [ABSTRACT FROM AUTHOR]

Prodigiosin, a red pigment produced by numerous bacterial species, exerts various antibiotic effects on prokaryotic and eukaryotic organisms. For instance, human carcinoma cell lines appear to suffer from endoplasmic reticulum (ER) stress in the presence of prodigiosin. Here, we demonstrated that prodigiosin also triggers the unfolded-protein response (UPR), which is a cytoprotective response against ER stress, in yeast Saccharomyces cerevisiae. An S. cerevisiae mutant carrying a UPR-deficient mutation was hypersensitive to prodigiosin. Our observations cumulatively indicate that protein folding in the ER is impaired by prodigiosin, illustrating a new mode of action.

In this study, novel biomaterial that consisted entirely of bacterial products was developed with the approach of designing cost effective material for biomedical applications. With this aim, bacterial cellulose membranes (BCMs) which synthesized by Komagataeibacter intermedius were produced. Moreover, to impart antimicrobial properties to enhance the capacity of BCMs for biomedical usage, prodigiosin (PG) pigment of Serratia marcescens which presents wide range of antimicrobial activities was loaded to BCMs. Firstly, high yield of PG production was achieved, and then crude pigment was purified with silica gel column. The purified PG was characterized with thin layer chromatography and UV–visible spectrometry. The antimicrobial effect of the produced pigment on Gram-positive and negative bacteria and a yeast was investigated. The success of modification in PG-modified BCMs has been demonstrated by FTIR and SEM. Moreover, antimicrobial and antiadhesive ability of novel PG-BCMs were examined with disc diffusion and plate counting methods. As a result, it was established that PG-BCMs were able to inhibit the growth of all tested microorganisms. Furthermore, excellent antiadhesive effect was observed for the tested microorganisms with the inhibition rates of 82.05–96.25 %. Finally, cytotoxicity test with L929 cell line demonstrated that PG-BCM is biocompatible at a level that can be applied in in vivo studies. • Prodigiosin pigment obtained from S. marcescens ATCC 14756 was used to impart antimicrobial properties to bacterial cellulose produced by K. intermedius. • Bacterial cellulose functionalized with prodigiosin showed excellent antimicrobial activity against both Gram-positive and negative bacteria. • Prodigiosin loaded bacterial cellulose membranes inhibited the adhesion capacity of both bacteria and Candida yeast. [ABSTRACT FROM AUTHOR]

Bioprospecting actinobacterial secondary metabolism from untapped marine sources may lead to the discovery of biotechnologically-relevant compounds. While studying the diversity and bioactive potential of Actinomycetota associated with Codium tomentosum, a green seaweed collected in the northern Portuguese cost, strain CT-F61, identified as Streptomyces violaceoruber, was isolated. Its extracts displayed a strong anticancer activity on breast carcinoma T-47D and colorectal carcinoma HCT116 cells, being effective as well against a panel of human and fish pathogenic bacteria. Following a bioactivity-guided isolation pipeline, a new analogue of the red-pigmented family of the antibiotics prodigiosins, decylprodigiosin (1), was identified and chemically characterized. Despite this family of natural products being well-known for a long time, we report a new analogue and the first evidence for prodigiosins being produced by a seaweed-associated actinomycete. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading threat to public health as it is resistant to most currently available antibiotics. Prodigiosin is a secondary metabolite of microorganisms with broad-spectrum antibacterial activity. This study identified a significant antibacterial effect of prodigiosin against MRSA with a minimum inhibitory concentration as low as 2.5 mg/L. The results of scanning electron microscopy, crystal violet staining, and confocal laser scanning microscopy indicated that prodigiosin inhibited biofilm formation in S. aureus USA300, while also destroying the structure of the cell wall and cell membrane, which was confirmed by transmission electron microscopy. At a prodigiosin concentration of 1.25 mg/L, biofilm formation was inhibited by 76.24%, while 2.5 mg/L prodigiosin significantly reduced the vitality of MRSA cells in the biofilm. Furthermore, the transcriptomic results obtained at 1/8 MIC of prodigiosin indicated that 235and 387 genes of S. aureus USA300 were significantly up- and downregulated, respectively. The downregulated genes were related to two-component systems, including the transcriptional regulator LytS, quorum sensing histidine kinases SrrB, NreA and NreB, peptidoglycan biosynthesis enzymes (MurQ and GlmU), iron-sulfur cluster repair protein ScdA, microbial surface components recognizing adaptive matrix molecules, as well as the key arginine synthesis enzymes ArcC and ArgF. The upregulated genes were mainly related to cell wall biosynthesis, as well as two-component systems including vancomycin resistance-associated regulator, lipoteichoic acid biosynthesis related proteins DltD and DltB, as well as the 9 capsular polysaccharide biosynthesis proteins. This study elucidated the molecular mechanisms through which prodigiosin affects the cell envelope of MRSA from the perspectives of cell wall synthesis, cell membrane and biofilm formation, providing new potential targets for the development of antimicrobials for the treatment of MRSA. [ABSTRACT FROM AUTHOR]

Prodigiosin (PG)—a molecule with promising applications in many fields—was effectively biosynthesized in this study using a novel and eco-friendly fermentation substrate—i.e., beer brewing by-product (BBB). It was confirmed as a nutrient-rich substrate source of protein (22.18%), ash (10.1%), carbohydrate (1.98%), sugar, and abundant mineral elements. The cultural medium with a newly designed formula on a small flask containing 1.25% BBB/Casein (9/1), 0.025% FeSO4, and 0.125% Na2HPO4 for a notable PG yield achieved 6230 mg/L after 48 h. PG production on a bioreactor system also enhanced yield by 1.16 folds (reaching 7220 mg/L) and shortened fermentation time (only taking 10 h). This pure pigment was isolated and identified by analyzing UV/vis absorption, MALDI-TOF MS, and HPLC. The obtained PG was used for antifungal tests. Notably, in this work, most of PG's pathogen fungal inhibition activity are new findings. Of those, PG showed the most positive effect on Colletotrichum gloeosporioides F05 strain (causing on sweet potato roots) with inhibition rates of mycelial growth and spore germination achieved at 47 and 57%, respectively. In particular, PG also reduced resistance and wholly inhibited mycelium growth germinating from spores. Furthermore, PG showed the good interaction ability with multiple target proteins (CDC42, CYP51, CAS2, Pectate lyase B, and Beta tubulin) inhibiting C. gloeosporioides via docking simulation. The results of this study revealed useful scientific information related to the novel application of BBB in PG production and the new PG's effects in the management of fungal pathogens in crops. [ABSTRACT FROM AUTHOR]

Prodigiosin is a tripyrrole red pigment that has been found to have antimicrobial, anticancer, and immunosuppressive properties. Experiments were conducted in this study to determine the best media types, temperature, and nitrogen and carbon sources for improving prodigiosin intracellular yield in Serratia marcescens. The nutrient broth (NB) medium at 30 °C yielded the highest level of prodigiosin (15 mg/L) when compared to peptone glycerol (PG), tryptone soy broth (TSB), Luria–Bertani broth (LBB), and glycerol beef broth (GBB). Lactose and peptone were found to be the most effective carbon and nitrogen sources, and when added to the nutrient broth, prodigiosin production increased to 18.67% (17.8 mg/L) and 22.67% (18.4 mg/L), respectively. To extract prodigiosin from Serratia marcescens biomass, the best ratio of organic solvent to water (pH 3) was 19: 1, and ethanol was found to be the best organic solvent to extract prodigiosin (15 mg/L) among DMSO, methanol, acetone, acetonitrile, and chloroform. To purify the prodigiosin, a column chromatography study was conducted, with Silica Gel 60–120 mesh as the stationary phase and a solvent mixture of chloroform, methanol, and acetone (4:2:3 v/v) as the mobile phase, yielding a purification yield of 65.39%. The absorption maximum of prodigiosin was found to be 535 nm in a UV–VIS study, and FTIR study confirmed that the functional group of prodigiosin is well matched with prior studies. The eluted fraction of the column contained 100% pure prodigiosin, which was validated by HPLC analysis. The LC–MS analysis also confirmed that prodigiosin was present in the eluted fraction of the column, with a peak at 324 m/z. When compared to the commercial pricing of prodigiosin on the worldwide market, modified media I (nutrient broth with 5% peanut), modified media II (nutrient broth with 5% sesame), and conventional media (nutrient broth) were determined to be economically feasible. The total saleable costs for 1 mg of prodigiosin obtained from modified media I, modified media II, and conventional media are 9229.41 INR (120.68 $), 14,502.66 INR (189.63 $), and 20,301.46 INR (265.45 $) respectively. The economic gain obtained from the modified media I, modified media II, and conventional media was found to be 362.27 $, 293.32 $, and 217.50 $ per mg of prodigiosin respectively. [ABSTRACT FROM AUTHOR]

Prodigiosin (PG) is a secondary metabolite produced by Serratia marcescens which has a promising future in food, textile, and other industries due to its bright color and diverse biological activities. Currently, the production of PG is mainly restricted by the components of the fermentation medium and large losses during its extraction process, making large-scale industrial production impossible. In this study, a Box–Behnken design (BBD) was used to optimize the response surface of the fermentation medium of S. marcescens. The optimum medium composition was found to be sucrose, 16.29 g/L; peptone, 11.76 g/L; and tween 80, 2.64 g/L. This composition produced a PG amount of 1653.95 ± 32.12 mg/L, which is a 64-fold increase compared to the initial medium. A Box–Behnken design (BBD) was then used to optimize the response surface of the extraction process of PG, aiming to reduce loss during extraction. The optimal extraction conditions were determined to be a solvent fermentation liquid ratio of 9.12:1, an extraction temperature of 25.35 °C, and an extraction time of 30.33 min. These conditions resulted in a final PG production amount of 2142.75 ± 12.55 mg/L, which was nearly 84 times higher than the initial production amount of PG. These results provide essential theoretical and experimental support for the industrial production of PG. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is known to generate bacterial biofilms that increase antibiotic resistance. With the increase of multi-drug resistance in recent years, the formulation of a new therapeutic strategy has seemed urgent. Preliminary findings show that Prodigiosin (PG), derived from chromium-resistant Serratia marcescens, exhibited efficient anti-biofilm activity against Staphylococcus aureus. However, its anti-biofilm activity against P. aeruginosa remains largely unexplored. The anti-biofilm activity of PG against three clinical single drug-resistant P. aeruginosa was evaluated using crystal violet staining, and the viability of biofilms and planktonic cells were also assessed. A model of chronic lung infection was constructed to test the in vivo antibiofilm activity of PG. The results showed that PG inhibited biofilm formation and effectively inhibited the production of pyocyanin and extracellular polysaccharides in vitro, as well as moderated the expression of interleukins (IL-1β, IL-6, IL-10) and tumor necrosis factor (TNF-α) in vivo, which might be attributed to the downregulation of biofilm-related genes such as algA, pelA, and pslM. These findings suggest that PG could be a potential treatment for drug-resistant P aeruginosa and chronic biofilm infections. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to determine which natural and inexpensive materials induced the highest production of prodigiosin pigment in local Serratia marcescens isolates. Furthermore, this study focused on purifying and identifying a single red pigment among several pigments in the crude extract of S. marcescens by HPLC. Methodology and results: Two isolates of S. marcescens (S1 and S2) were isolated from urine and a urinary catheter. Isolates were identified based on the red color of colonies when growing on nutrient agar medium incubated at 28 °C, which gave an adverse reaction to Gram stain; the diagnosis was completed with several biochemical tests. The highest yield of this pigment was investigated using Luria-Bertani (LB) medium supplemented with available materials (sesame, peanut, and coconut meat seed powders). Results showed that LB containing sesame powder medium induced the highest prodigiosin production in S1 and S2 isolates (179.398 and 107.280 unit/cell, respectively). On the other hand, S1 and S2 isolates on LB supplemented with peanut medium produced 150.492 and 93.970 units/cell of prodigiosin, respectively. However, coconut meat supplement through LB failed to induce bacteria to synthesize the pigment. The pigment was identified in a retention time equal to 2.2 min through crude extraction and prodigiosin (with red color) was purified successfully by the preparative-HPLC technique. Conclusion, significance and impact of study: This study successfully showed that natural and inexpensive products were able to induce prodigiosin pigment production from local S. marcescens isolates. Results showed that sesame seed powder was the best carbon source that induced prodigiosin, followed by peanut seed powder. Prodigiosin was identified and purified successfully by the preparative-HPLC technique. Research findings suggest that low-cost materials could be used to reduce the cost of prodigiosin production. [ABSTRACT FROM AUTHOR]

Serratia marcescens commonly synthesize a red pigment known as prodigiosin. Prodigiosin is considered a promising pharmaceutical due to its documented properties of having antimicrobial, anticancer, and immunosuppressive effects. This investigation involved the isolation of Serratia marcescens, a bacterium capable of producing prodigiosin, from grey water samples collected in Nnamdi Azikiwe University Awka campus, Nigeria. The central composite design (CCD) of the experiment was applied to generate a set of 31 experimental combinations to study the optimal conditions for pigment production using nutrient broth supplemented with glucose as a fermentation medium. A regression model that described the relationship between the test variables for optimum prodigiosin yield was developed. The regression coefficient (R2) value of 72.48% implied adequate model fitness. The optimal conditions identified were 24 g/L glucose concentration, pH 7.2, 2.4 mL inoculum size, and 180 rpm agitation speed. A 4.25-fold increase in prodigiosin yield was recorded in optimized condition than in unoptimized condition. Antimicrobial activity against E. coli and Candida albicans shows that prodigiosin has significantly higher activity than the conventional antibiotics tested. Our results indicate that prodigiosin production by Serratia marcescens can be enhanced using statistical models, and the pigment can be an alternative to conventional antibiotics for treating microbial infections.

Abstract Background The bacterial secondary metabolite prodigiosin has been shown to exert anticancer, antimalarial, antibacterial and immunomodulatory properties. With regard to cancer, it has been reported to affect cancer cells but not non-malignant cells, rendering prodigiosin a promising lead compound for anticancer drug discovery. However, a direct protein target has not yet been experimentally identified. Methods We used mass spectrometry-based thermal proteome profiling in order to identify target proteins of prodigiosin. For target validation, we employed a genetic knockout approach and electron microscopy. Results We identified the Golgi stacking protein GRASP55 as target protein of prodigiosin. We show that prodigiosin treatment severely affects Golgi morphology and functionality, and that prodigiosin-dependent cytotoxicity is partially reduced in GRASP55 knockout cells. We also found that prodigiosin treatment results in decreased cathepsin activity and overall blocks autophagic flux, whereas co-localization of the autophagosomal marker LC3 and the lysosomal marker LAMP1 is clearly promoted. Finally, we observed that autophagosomes accumulate at GRASP55-positive structures, pointing towards an involvement of an altered Golgi function in the autophagy-inhibitory effect of this natural compound. Conclusion Taken together, we propose that prodigiosin affects autophagy and Golgi apparatus integrity in an interlinked mode of action involving the regulation of organelle alkalization and the Golgi stacking protein GRASP55. Video Abstract

Abstract The paper presents the results of the experimental and analytical study of targeted drug-loaded polymer-based microspheres made from blend polymer of polylactic-co-glycolic acid and polycaprolactone (PLGA-PCL) for targeted and localized cancer drug delivery. In vitro sustained release with detailed thermodynamically driven drug release kinetics, over a period of three months using encapsulated targeted drugs (prodigiosin-EphA2 or paclitaxel-EphA2) and control drugs [Prodigiosin (PGS), and paclitaxel (PTX)] were studied. Results from in vitro study showed a sustained and localized drug release that is well-characterized by non-Fickian Korsmeyer–Peppas kinetics model over the range of temperatures of 37 °C (body temperature), 41 °C, and 44 °C (hyperthermic temperatures). The in vitro alamar blue, and flow cytometry assays in the presence of the different drug-loaded polymer formulations resulted to cell death and cytotoxicity that was evidence through cell inhibition and late apoptosis on triple negative breast cancer (TNBC) cells (MDA-MB 231). In vivo studies carried out on groups of 4-week-old athymic nude mice that were induced with subcutaneous TNBC, showed that the localized release of the EphA2-conjugated drugs was effective in complete elimination of residual tumor after local surgical resection. Finally, ex vivo histopathological analysis carried out on the euthanized mice revealed no cytotoxicity and absence of breast cancer metastases in the liver, kidney, and lungs 12 weeks after treatment. The implications of the results are then discussed for the development of encapsulated EphA2-conjugated drugs formulation in the specific targeting, localized, and sustain drug release for the elimination of local recurred TNBC tumors after surgical resection. Graphical Abstract

[Objective] In order to improve the yield of prodigiosin, the fermentation conditions of a strain of Klebsiella oxytoca P3 isolated and preserved in the laboratory to produce prodigiosin were optimized. [Method] The composition and molecular weight of the extract were analyzed by liquid chromatography-mass spectrometry (LC-MS), and the fermentation conditions (temperature, pH, NaCl concentration, inducing sugar) of P3 were studied by shaking flask culture. [Result]The red pigment produced by fermentation culture was proved to be prodigiosin by LC-MS analysis, with a molecular weight of 324. 27. The optimum fermentation conditions for P3 production of prodigiosin were determined as follows:24 ℃, pH 7. 2-8. 0, NaCl concentration 0. 05%-0. 10%, 2% fructose induction. [Conclusion] The fermentation product of Klebsiella P3 was prodigiosin, and the optimized yield of prodigiosin was 90-130 mg / L. [ABSTRACT FROM AUTHOR]

Pseudomonas species have become promising cell factories for the production of natural products due to their inherent robustness. Although these bacteria have naturally evolved strategies to cope with different kinds of stress, many biotechnological applications benefit from engineering of optimised chassis strains with specially adapted tolerance traits. Here, we explored the formation of outer membrane vesicles (OMV) of Pseudomonas putida KT2440. We found OMV production to correlate with the recombinant production of a natural compound with versatile beneficial properties, the tripyrrole prodigiosin. Further, several P. putida genes were identified, whose up‐ or down‐regulated expression allowed controlling OMV formation. Finally, genetically triggering vesiculation in production strains of the different alkaloids prodigiosin, violacein, and phenazine‐1‐carboxylic acid, as well as the carotenoid zeaxanthin, resulted in up to three‐fold increased product yields. Consequently, our findings suggest that the construction of robust strains by genetic manipulation of OMV formation might be developed into a useful tool which may contribute to improving limited biotechnological applications. [ABSTRACT FROM AUTHOR]

Prodigiosin is a red pigment commonly produced as a secondary metabolite by Serratia marcescens. It exhibits inherent bioactivities, including antimicrobial and anticancer, with low to no toxic effects on normal cells. The present study investigates a bioactive prodigiosin production from an atypical, red-pigmented, potentially novel Janthinobacterium sp. ERMR3:09 isolated from a glacial moraine. Statistically optimized culture parameters, i.e., w/v 1.0% glucose and 0.08% peptone as carbon and nitrogen sources, temperature 20 °C, and media pH 7, resulted in a four-fold increase in the pigment yield. The upscaled production in an 8 L volume resulted in higher pigment production within a shorter period of 48 h. The ultra-performance liquid chromatography (UPLC) analysis validated the identity of the purified pigment as prodigiosin that showed thermostability at 75 °C for 3 h. Evaluation of antimicrobial activity showed potent inhibitory effects (> 50%) against the opportunistic pathogenic fungal and Gram-positive bacterial strains. The pigment showed significant cytotoxicity (p < 0.05) towards A549 and HeLa cell lines with IC50 values of 42.2 μM and 36.11 μM, respectively. The study demonstrated that microbial communities from extreme niches can be ideal sources of bioactive pigments with immense pharmaceutical potential vital for the development of non-synthetic therapeutic agents. [ABSTRACT FROM AUTHOR]

Prodigiosin is a bacterial pigment with therapeutic and antimicrobial properties. Although traditionally produced by Serratia marcescens, alternative methods based on agroindustrial waste are being explored. This research focused on determining the feasibility of obtaining prodigiosin using hydrolysates of Tilapia scales by Serratia marcescens QSC23, isolated from the La Libertad region in Peru. Wastewater from a treatment plant was collected and enriched in a Luria-Bertani medium to isolate colonies of the Serratia genus. These colonies were characterized morphologically, biochemically, and using molecular techniques, including 16S rDNA gene sequencing. Tilapia scales were obtained and subjected to alkaline hydrolysis to produce hydrolysates, which served as a culture medium for prodigiosin production. Different conditions of stirring speed (100 - 250 rpm) and NaCl (0.5 - 2.5%) were evaluated for prodigiosin production over a 72 h incubation period at an initial pH of 7 and 25 ℃. QSC23 was able to produce prodigiosin, with a maximum production of 516.03 ± 15.84 units per cell under conditions of 150 rpm and 1.5 % NaCl from the fermentation of tilapia scale hydrolysates. The chemical characterization of the pigment was confirmed using UV-VIS spectroscopy methods. Serratia marcescens QSC23 demonstrated the ability to produce prodigiosin using fermentation residues from tilapia scales. This sustainable and cost-effective production offers a promising avenue for the global market of natural pigments. [ABSTRACT FROM AUTHOR]

Prodigiosin (PG) is chemically formulated as 4-methoxy-5-[(5-methyl-4-pentyl-2H-pyrrol-2ylidene)methyl]-2,2′-bi-1H-pyrrole and it is an apoptotic agent. Only a few protein targets for PG have been identified so far for regulating various diseases; nevertheless, finding more PG targets is crucial for novel drug discovery research. A bioinformatics method was applied in this work to find additional potential PG targets. Initially, a text mining analysis was conducted to determine the relationship between PG and a variety of metabolic processes. One hundred sixteen proteins from the KEGG pathway were selected for the docking study. Inverse virtual screening was performed by Discovery Studio software 4.1 using CHARMm-based docking tool. Twelve proteins are screened out of 116 because their CDOCKER interaction energy is larger than − 40.22 kcal/mol. The best docking score with PG was reported to be − 44.25 kcal/mol, − 44.99 kcal/mol, and − 40.91 kcal/mol for three novel proteins, such as human epidermal growth factor-2 (HER-2), mitogen-activated protein kinase (MEK), and S6 kinase protein (S6K) respectively. The interactions in the S6K/PG complex are predominantly hydrophobic; however, hydrogen bond interactions can be identified in the MEK/PG and HER-2/PG complexes. The root-mean-square deviation (RMSD) and key interaction score system (KISS) were further used to validate the docking approach. The docking approach employed in this work has a low RMSD value (2.44 Å) and a high KISS score (0.5), indicating that it is significant. [ABSTRACT FROM AUTHOR]

Microbial life present in the marine environment has to be able to adapt to rapidly changing and often extreme conditions. This makes these organisms a putative source of commercially interesting compounds since adaptation provides different biochemical routes from those found in their terrestrial counterparts. In this work, the goal was the identification of a marine bacterium isolated from a sample taken at a shallow water hydrothermal vent and of its red product. Genomic, lipidomic, and biochemical approaches were used simultaneously, and the bacterium was identified as Serratia rubidaea. A high-throughput screening strategy was used to assess the best physico-chemical conditions permitting both cell growth and production of the red product. The fatty acid composition of the microbial cells was studied to assess adaptation at the lipid level under stressful conditions, whilst several state-of-the-art techniques, such as DSC, FTIR, NMR, and Ultra-High Resolution Qq-Time-of-Flight mass spectrometry, were used to characterize the structure of the pigment. We hypothesize that the pigment, which could be produced by the cells up to 62 °C, is prodigiosin linked to an aliphatic compound that acts as an anchor to keep it close to the cells in the marine environment. [ABSTRACT FROM AUTHOR]

Prodigiosin, a red pigment produced by Hahella chejuensis, a marine-derived microorganism, has several biological functions, including antimicrobial activity and inflammatory relief. In this study, the antibacterial activity of prodigiosin against skin microorganisms was explored. Paper disc assay on skin bacterial cells revealed that Cutibacterium acnes related to acne vulgaris highly susceptible to prodigiosin. MIC (Minimal Inhibitory Concentration) and MBC (Minimal Bactericidal Concentration) were determined on Cutibacterium species. The RNA-seq analysis of prodigiosin-treated C. acnes cells was performed to understand the antibacterial mechanism of prodigiosin. Among changes in the expression of hundreds of genes, the expression of a stress-responsive sigma factor encoded by sigB increased. Conversely, the gene expression of cell wall biosynthesis and energy metabolism was inhibited by prodigiosin. Specifically, the expression of genes related to the metabolism of porphyrin, a pro-inflammatory metabolite, was significantly reduced. Therefore, prodigiosin could be used to control C. acnes. Our study provided new insights into the antimicrobial mechanism of prodigiosin against C. acnes strains. [ABSTRACT FROM AUTHOR]

The raising concern of drug resistance, having substantial impacts on public health, has instigated the search of new natural compounds with substantial medicinal activity. In order to find out a natural solution, the current study has utilized prodigiosin, a linear tripyrrole red pigment, as an active ingredient to control bacterial proliferation and prevent cellular oxidation caused by ROS (Reactive Oxygen Species). A prodigiosin-producing bacterium BRL41 was isolated from the ancient Barhind soil of BCSIR Rajshahi Laboratories, Bangladesh, and its morphological and biochemical characteristics were investigated. Whole genome sequencing data of the isolate revealed its identity as Serratia sp. and conferred the presence of prodigiosin gene cluster in the bacterial genome. "Prodigiosin NRPS", among the 10 analyzed gene clusters, showed 100% similarity with query sequences where pigC, pigH, pigI, and pigJ were identified as fundamental genes for prodigiosin biosynthesis. Some other prominent clusters for synthesis of ririwpeptides, yersinopine, trichrysobactin were also found in the chromosome of BRL41, whilst the rest displayed less similarity with query sequences. Except some first-generation beta-lactam resistance genes, no virulence and resistance genes were found in the genome of BRL41. Structural illumination of the extracted red pigment by spectrophotometric scanning, Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and change of color at different pH solutions verified the identity of the isolated compound as prodigiosin. Serratia sp. BRL41 attained its maximum productivity 564.74 units/cell at temperature 30˚C and pH 7.5 in two-fold diluted nutrient broth medium. The compound exhibited promising antibacterial activity against Gram-positive and Gram-negative bacteria with MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) values ranged from 3.9 to15.62 μg/mL and 7.81 to 31.25 μg/mL respectively. At concentration 500 μg/mL, except in Salmonella enterica ATCC-10708, prodigiosin significantly diminished biofilm formed by Listeria monocytogens ATCC-3193, Pseudomonas aeruginosa ATCC-9027, Escherichia coli (environmental isolate), Staphylococcus aureus (environmental isolate). Cellular glutathione level (GSH) was elevated upon application of 250 and 500 μg/mL pigment where 125 μg/mL failed to show any free radical scavenging activity. Additionally, release of cellular components in growth media of both Gram-positive and Gram-negative bacteria were facilitated by the extract that might be associated with cell membrane destabilization. Therefore, the overall findings of antimicrobial, antibiofilm and antioxidant activities suggest that in time to come prodigiosin might be a potential natural source to treat various diseases and infections. [ABSTRACT FROM AUTHOR]

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Bacterial pigments represent a diverse group of secondary metabolites, which confer fitness advantages to the producers while residing in communities. The bioactive potential of such metabolites, including antimicrobial, anticancer, and immunomodulation, are being explored. Reckoning that a majority of such pigments are produced in response to quorum sensing (QS) mediated expression of biosynthetic gene clusters and, in turn, influence cell–cell communication, systemic profiling of the pigments for possible impact on QS appears crucial. A systemic screening of bacterial pigments for QS-inhibition combined with exploration of antibiofilm and antimicrobial action against Acinetobacter baumannii might offer viable alternatives to combat the priority pathogen. Major bacterial pigments are classified (clustered) based on their physicochemical properties, and representatives of the clusters are screened for QS inhibition. The screen highlighted prodigiosin as a potent quorum quencher, although its production from Serratia marcescens appeared to be QS-independent. In silico analysis indicated potential interactions between AbaI and AbaR, two major QS regulators in A. baumannii, and prodigiosin, which impaired biofilm formation, a major QS-dependent process in the bacteria. Prodigiosin augmented antibiotic action of ciprofloxacin against A. baumannii biofilms. Cell viability analysis revealed prodigiosin to be modestly cytotoxic against HEK293, a non-cancer human cell line. While developing dual-species biofilm, prodigiosin producer S. marcescens significantly impaired the fitness of A. baumannii. Enhanced susceptibility of A. baumannii toward colistin was also noted while growing in co-culture with S. marcescens. Antibiotic resistant isolates demonstrated varied responsiveness against prodigiosin, with two resistant strains demonstrating possible collateral sensitivity. Collectively, the results underpin the prospect of a prodigiosin-based therapeutic strategy in combating A. baumannii infection. [ABSTRACT FROM AUTHOR]

Regulation of prodigiosin biosynthesis is received wide attention due to the antimicrobial, immunosuppressive and anticancer activities of prodigiosin. Here, we constructed a transposon mutant library in S. marcescens FS14 to identify genes involved in the regulation of prodigiosin biosynthesis. 62 strains with apparently different colors were obtained. Identification of the transposon insertion sites revealed that they are classified into three groups: the coding region of cyaA and two component system eepS/R and the promoter region of rpoH. Since the effect of cyaA and eepS/R genes on prodigiosin was extensively investigated in Serratia marcescens, we chose the mutant of rpoH for further investigation. Further deletion mutation of rpoH gene showed no effect on prodigiosin production suggesting that the effect on prodigiosin production caused by transposon insertion is not due to the deletion of RpoH. We further demonstrated that multicopy expression of RpoH reduced prodigiosin biosynthesis indicating that transposon insertion caused RpoH enhanced expression. Previous results indicate that RpoS is the sigma factor for transcription of pig gene cluster in FS14, to test whether the enhanced expression of RpoH prevents prodigiosin by competing with RpoS, we found that multicopy expression of RpoS could alleviate the prodigiosin production inhibition by enhanced RpoH. We proposed that multicopy expressed RpoH competes with RpoS for core RNA polymerase (RNAP) resulting in decreased transcription of pig gene cluster and prodigiosin production reduction. We also demonstrated that RpoH is not directly involved in prodigiosin biosynthesis. Our results suggest that manipulating the transcription level of sigma factors may be applied to regulate the production of secondary metabolites. [ABSTRACT FROM AUTHOR]

Abstract A novel red-pigmented bacterium was isolated from a water sample collected at Osun River, Ede. Morphological and 16 S rRNA gene sequencing revealed that the bacterium is a strain of Brevundimonas olei, while its red pigment was identified using UV-visible, FTIR and GCMS as a derivative of propylprodigiosin. The maximum absorbance of 534 nm, the FTIR’s 1344 cm− 1 peak of prodigiosin’s methoxyl C-O interaction, and the molecular ions from GCMS confirmed the pigment’s identity. The pigments production was temperature-sensitive (25 °C), lost at > 28 °C, and in the presence of urea and humus. In addition, the pigment turned pink in the presence of hydrocarbons, while its red colour was retained with KCN and Fe2SO4, and enhanced by methylparaben. Furthermore, the pigment is stable in high temperature, salt, and acidic conditions, but changed to yellow in alkaline solution. The pigment, identified as propylprodigiosin (m/z 297), demonstrated broad-spectrum antibacterial activities against clinically important strains of Staphylococcus aureus (ATCC25923), Pseudomonas aeruginosa (ATCC9077), Bacillus cereus (ATCC10876), Salmonella typhi (ATCC13311), and Escherichia coli (DSM10974). The ethanol extract has the highest zones of inhibition of 29 ± 3.0, 26 ± 1.2, 22 ± 3.0, 22 ± 1.5, and 20 ± 2.0 mm, respectively. Furthermore, the acetone pigments interacted with cellulose and glucose such that increasing glucose concentrations showed linearity at 425 nm. Finally, the fastness of the pigments to fabrics was excellent, with percentage fadedness of 0 and − 43% light and washing tests, respectively, in the presence of Fe2SO4 as the mordant. The antibacterial nature of prodigiosin solutions and their good textile fastness to fabrics could be essential in manufacturing antiseptic materials such as bandages, hospital clothing and agricultural applications such as tubers preservation. Key points

Although Serratia marcescens is known for its natural ability to produce the red pigment prodigiosin, it has been little explored as a biocatalyst in bioelectrochemical systems (BES). Here, we have employed an environmental S. marcescens isolate S734 as biocatalyst in a microbial fuel cell (MFC) anode to oxidize glycerol and to produce energy; we have evaluated how the anode behaves in three conditions: (i) as an abiotic electrode (FC-A); (ii) as a biotic electrode after S. marcescens biofilm growth (MFC-B); and (iii) as an abiotic electrode added with the supernatant containing prodigiosin (FC-P). Scanning electron microscopy and electrochemical measurements indicated that prodigiosin formed a conductive film over FC-P, which increased charge transfer by 424 times compared to FC-A. The maximum power density during the FC-P operation was 10.0 mW/m−2. Nevertheless, only in the presence of S. marcescens (MFC-B) was glycerol oxidized and electricity generated. Cyclic voltammetry indicated that the prodigiosin was the electrochemical active substance in the supernatant, and that its process was irreversible and controlled by adsorption. Electrochemical impedance spectroscopy confirmed that the prodigiosin-containing supernatant decreased the load resistance from 8396.3 Ω in FC-A to 58.10 Ω in FC-P. Genomic analysis showed that the prodigiosin biosynthesis gene cluster in strain S734 belonged to the Serratia 274 type, which contains pigA to pigN genes flanked by cueR and copA homologues. In conclusion, the supernatant produced by S. marcescens strain S734, containing prodigiosin could be explored as a green conductor in BES without further purification steps.

Background: The bacterial secondary metabolite prodigiosin has been shown to exert anticancer, antimalarial, antibacterial and immunomodulatory properties. With regard to cancer, it has been reported to affect cancer cells but not non-malignant cells, rendering prodigiosin a promising lead compound for anticancer drug discovery. However, a direct protein target has not yet been experimentally identified. Methods: We used mass spectrometry-based thermal proteome profiling in order to identify target proteins of prodigiosin. For target validation, we employed a genetic knockout approach and electron microscopy. Results: We identified the Golgi stacking protein GRASP55 as target protein of prodigiosin. We show that prodigiosin treatment severely affects Golgi morphology and functionality, and that prodigiosin-dependent cytotoxicity is partially reduced in GRASP55 knockout cells. We also found that prodigiosin treatment results in decreased cathepsin activity and overall blocks autophagic flux, whereas co-localization of the autophagosomal marker LC3 and the lysosomal marker LAMP1 is clearly promoted. Finally, we observed that autophagosomes accumulate at GRASP55-positive structures, pointing towards an involvement of an altered Golgi function in the autophagy-inhibitory effect of this natural compound. Conclusion: Taken together, we propose that prodigiosin affects autophagy and Golgi apparatus integrity in an interlinked mode of action involving the regulation of organelle alkalization and the Golgi stacking protein GRASP55. 8brCwiZ4E3PVMoFvaLMguT Video Abstract [ABSTRACT FROM AUTHOR]

Serratia marcescens is a gram-negative bacterium that is able to produce many secondary metabolites, such as the prominent red pigment prodigiosin (PG). In this work, a ptrA-disrupted mutant strain with reduced PG production was selected from Tn5 transposon mutants. RT–qPCR results indicated that ptrA promoted elevated transcription of the pig gene cluster in S. marcescens FZSF02. Furthermore, we found that ptrA also controls several other important biological functions of S. marcescens, including swimming and swarming motilities, biofilm formation, hemolytic activity, and stress tolerance. In conclusion, this study demonstrates that ptrA is a PG synthesis-promoting factor in S. marcescens and provides a brief understanding of the regulatory mechanism of ptrA in S. marcescens cell motility and hemolytic activity. [ABSTRACT FROM AUTHOR]