Prodigiosin derived from chromium-resistant Serratia sp. prevents inflammation and modulates gut microbiota homeostasis in DSS-induced colitis mice.

Prodigiosin (PG) is a secondary metabolite of microorganisms with anticancer, antimalarial, antibacterial and immunomodulatory effects. However, the modulatory effects on gut microbiome and intestinal immune microenvironment have never been explored in the ulcerative colitis (UC) mice model. In this study, 2.5% dextran sulfate sodium (DSS) induced UC mice model was constructed to investigate the effects of PG derived from a chromium-resistant Serratia sp. on the intestinal flora and inflammatory response. The results showed that prodigiosin administration attenuated the DSS-induced UC symptoms, including preventing the reduction of colonic length and DSS-induced mortality. Furthermore, prodigiosin ameliorated the DSS-induced gut microbiota community dysbiosis by restoring the abundance of Bacteroidota. At the genus level, the declined abundance of Bifidobacterium, Allobaculum and Akkermannia in UC mice was elevated by the treatment of PG. Pathological results by H&E staining showed that PG prevented the appearance of distortion and atrophy of crypt and neutrophil infiltration in a dose-dependent manner. RT-PCR revealed that the expression levels of the inflammatory factors IL-1ß, IL-6 and IL-10 were significantly suppressed, and the expression of the intestinal tight junction protein Claudin-1, Occludin and ZO-1 were upregulted in PG-treated UC mice. Conclusively, our results revealed that prodigiosin effectively prevented inflammatory response and protected intestinal barrier integrity of DSS-induced colitis mice via modulating gut microbiota community structure, suppressing inflammatory factors' expression, and accelerating the expression of intestinal tight junction protein. These results will provide new insights into the interaction of prodigiosin with intestinal microbiota homeostasis and its application in clinical against inflammatory bowel disease.

Advancing PHBV Biomedical Potential with the Incorporation of Bacterial Biopigment Prodigiosin.

The quest for sustainable biomaterials with excellent biocompatibility and tailorable properties has put polyhydroxyalkanoates (PHAs) into the research spotlight. However, high production costs and the lack of bioactivity limit their market penetration. To address this, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was combined with a bacterial pigment with strong anticancer activity, prodigiosin (PG), to obtain functionally enhanced PHBV-based biomaterials. The samples were produced in the form of films 115.6-118.8 µm in thickness using the solvent casting method. The effects of PG incorporation on the physical properties (morphology, biopolymer crystallinity and thermal stability) and functionality of the obtained biomaterials were investigated. PG has acted as a nucleating agent, in turn affecting the degree of crystallinity, thermal stability and morphology of the films. All samples with PG had a more organized internal structure and higher melting and degradation temperatures. The calculated degree of crystallinity of the PHBV copolymer was 53%, while the PG1, PG3 and PG3 films had values of 64.0%, 63.9% and 69.2%, respectively. Cytotoxicity studies have shown the excellent anticancer activity of films against HCT116 (colon cancer) cells, thus advancing PHBV biomedical application potential.

Antioxidant prodigiosin-producing cold-adapted Janthinobacterium sp. ERMR3:09 from a glacier moraine: Genomic elucidation of cold adaptation and pigment biosynthesis.

Janthinobacterium from cold niches has been studied broadly for bioactive violacein production. However, reports on the atypical red-pigmented Janthinobacterium strains are shallow. The bioactive red prodigiosin pigment has immense pharmacological significance, including antioxidant, antimicrobial and anticancer potential. Here, we report the first complete genome of a prodigiosin-producing Janthinobacterium sp. ERMR3:09 from Sikkim Himalaya in an attempt to elucidate its cold adaptation and prodigiosin biosynthesis. Nanopore sequencing and Flye assembly of the ERMR3:09 genome resulted in a single contig of 6,262,330 bp size and 62.26% GC content. Phylogenomic analysis and genome indices indicate that ERMR3:09 is a potentially novel species of the genus Janthinobacterium. The multicopy cold-responsive genes and gene upregulation under cold stress denoted its cold adaptation mechanisms. Genome analysis identified the unique genes, gene cluster and pathway for prodigiosin biosynthesis in ERMR3:09. Considering the notable antioxidant activity, it can be the next powerhouse of bioactive prodigiosin production.

Crystal structure of prodigiosin binding protein PgbP, a GNAT family protein, in Serratia marcescens FS14.

Acetylation is a conserved modification catalyzed by acetyltransferases that play prominent roles in a large number of biological processes. Members of the general control non-repressible 5 (GCN5)-N-acetyltransferase (GNAT) protein superfamily are widespread in all kingdoms of life and are characterized by highly conserved catalytic fold, and can acetylate a wide range of substrates. Although the structures and functions of numerous eukaryotic GNATs have been identified thus far, many GNATs in microorganisms remain structurally and functionally undescribed. Here, we determined the crystal structure of the putative GCN5-N-acetyltransferase PgbP in complex with CoA in Serratia marcescens FS14. Structural analysis revealed that the PgbP dimer has two cavities, each of which binds a CoA molecule via conserved motifs of the GNAT family. In addition, the biochemical studies showed that PgbP is a prodigiosin-binding protein with high thermal stability. To our knowledge, this is the first view of GNAT binding to secondary metabolites and it is also the first report of prodigiosin binding protein. Molecular docking and mutation experiments indicated that prodigiosin binds to the substrate binding site of PgbP. The structure-function analyses presented here broaden our understanding of the multifunctionality of GNAT family members and may infer the mechanism of the multiple biological activities of prodigiosin.

Structures, biosynthesis, and bioactivities of prodiginine natural products.

Prodiginines are a large family of microbial secondary metabolites with a core structure of tripyrrole rings. They exhibit not only diverse chemical structures but also rich biological activities, such as anti-cancer, anti-microbial, anti-algae, anti-parasitic, pesticides, and UV radiation resistance. The preferred cytotoxicity to cancer cells rather than normal cells indicates a good biological selectivity and safety, which makes the prodiginines promising candidates for drug development and novel additives for food processing. Until now, 33 prodiginine natural products have been identified in various bacteria, including Serratia, Hahella, Pseudoalteromonas, Vibrio, Zooshikella, Streptomyces, and Actinomadura. However, most efforts are still focused on the star molecule prodigiosin, while little yet is known about other prodiginine members, which retards the research and application of prodiginine compounds. To gain insight into the prodiginine family, we reviewed the recent discoveries on their chemical structures, biosynthesis, biological activities, and mechanisms of action. We believe this article will provide a guideline for new research on prodiginines, such as the discovery of new congeners and drug development. KEY POINTS: • The prodiginines are a large family of natural products with a core structure of tripyrrole rings and exhibit various bioactivities. • The prodiginines have a widespread distribution among many environmental microbes and diverse biosynthetic pathways, indicating important ecological roles and a great potential for new congeners. • The potent biological activities and good selectivity of action make prodiginines good lead compounds for drug development.

Prodigiosin inhibits the proliferation of glioblastoma by regulating the KIAA1524/PP2A signaling pathway.

Prodigiosin (PG), a member of a family of natural red pigments produced by a variety of bacteria, was first discovered in Serratia marcescens. PG has been reported to have an apoptosis-inducing effect in many cancers, such as lymphoma, colon cancer and nasopharyngeal carcinoma. For this study, we used three glioblastoma (GBM) cell lines (LN229, U251 and A172) to explore the effect of prodigiosin on GBM cells. A CCK8 assay was used to evaluate cell viability. We determinedthe cell cycle distribution by flow cytometry and measured proliferation by an EdU incorporation assay. The expression of different molecules was investigated by western blotting and RT-PCR. We further confirmed our results by plasmid transfection and lentiviral transduction. The LN229 xenograft model was used to study the effect of prodigiosin in vivo. We confirmed that prodigiosin played an anticancer role in several GBM cell lines through the KIAA1524/PP2A/Akt signalling pathway. Prodigiosin inhibited the protein expression of KIAA1524 by suppressing its transcription, which led to activation of PP2A. Afterward, PP2A inhibited the phosphorylation of Akt, thereby inducing increased expression of p53/p21. Furthermore, it was verified that prodigiosin inhibited the KIAA1524/PP2A/Akt axis in vivo in the LN229 xenograft model. These data improve the understanding of the anticancer effects of prodigiosin and further highlight the potential of prodigiosin for the development of anti-glioma drugs.

Prodigiosin from Serratia Marcescens in Cockroach Inhibits the Proliferation of Hepatocellular Carcinoma Cells through Endoplasmic Reticulum Stress-Induced Apoptosis.

Hepatocellular carcinoma (HCC) is the most common primary liver malignant tumor, and the targeted therapy for HCC is very limited. Our previous study demonstrated that prodigiosin(PG), a secondary metabolite from Serratia marcescens found in the intestinal flora of cockroaches, inhibits the proliferation of HCC and increases the expression of CHOP, a marker protein for endoplasmic reticulum stress (ERS)-mediated apoptosis, in a dose-dependent manner. However, the mechanisms underlying the activity of PG in vivo and in vitro are unclear. This study explored the molecular mechanisms of PG-induced ERS against liver cancer in vitro and in vivo. The apoptosis of hepatocellular carcinoma cells induced by PG through endoplasmic reticulum stress was observed by flow cytometry, colony formation assay, cell viability assay, immunoblot analysis, and TUNEL assay. The localization of PG in cells was observed using laser confocal fluorescence microscopy. Flow cytometry was used to detect the intracellular Ca2+ concentration after PG treatment. We found that PG could promote apoptosis and inhibit the proliferation of HCC. It was localized in the endoplasmic reticulum of HepG2 cells, where it induces the release of Ca2+. PG also upregulated the expression of key unfolded response proteins, including PERK, IRE1α, Bip, and CHOP, and related apoptotic proteins, including caspase3, caspase9, and Bax, but down-regulated the expression of anti-apoptotic protein Bcl-2 in liver cancer. Alleviating ERS reversed the above phenomenon. PG had no obvious negative effects on the functioning of the liver, kidney, and other main organs in nude mice, but the growth of liver cancer cells was inhibited by inducing ERS in vivo. The findings of this study showed that PG promotes apoptosis of HCC by inducing ERS.

Chitosan based micro and nano-particulate delivery systems for bacterial prodigiosin: Optimization and toxicity in animal model system.

Prodigiosin, a red bacterial pigment is a compound with promising therapeutic properties. Major hindrance in applying prodigiosin in pharmaceutics is the insolubility in water and lack of bioavailability. This study aims to optimize two different types of chitosan based delivery systems, microspheres and nanoparticles for prodigiosin derived from Serratia marcescens NITDPER1 through Taguchi method and determine toxicity perspectives. The results revealed 0.5 % chitosan, 1 % sodium-alginate and 5 % CaCl2 optimum for microsphere and 0.1 % chitosan, 1.5 % TPP and 1.5 % acetic acid for nanoparticle with the entrapment efficiency and maximum release of 89.27 ± 1.2 % and 87.42 ± 1.9 % for microspheres and 96.36 ± 1.7 % and 91.58 ± 2.1 % for nanoparticles. Particle size was 93.03 ± 0.3 µm and 75.1 ± 1.4 nm for micro and nanoformulations. Kinetic parameters of release fitted best with Korsmeyer-Peppas model. Swelling index of microsphere and nanoparticles in pH 6.8 was 799 ± 7.1 % and 35.3 ± 2.1 % respectively. FESEM, FT-IR and XRD revealed spherical morphology, preservation of prodigiosin functional groups and amorphous nature of the formulations. Anticancer IC50 values were (µg mL-1) 11.7 ± 1.2, 10.8 ± 1.4 and 9.4 ± 0.8 for free prodigiosin, microsphere and nanoparticles respectively. Toxicity studies on HEK-293 cell line, Daphnia magna and zebrafish model determined non-toxic nature of the bacterial prodigiosin and its formulations revealing suitability of animal system application.

Antimicrobial Biosynthetic Potential and Phylogenetic Analysis of Culturable Bacteria Associated with the Sponge Ophlitaspongia sp. from the Yellow Sea, China.

Sponge-derived bacteria are considered to be a promising source of novel drugs, owing to their abundant secondary metabolites that have diverse biological activities. In this study, we explored the antimicrobial biosynthetic potential and phylogenetics of culturable bacteria associated with the sponge Ophlitaspongia sp. from the Yellow Sea, China. Using culture-dependent methods, we obtained 151 bacterial strains, which were then analysed for their antimicrobial activities against seven indicator strains. The results indicate that 94 (62.3%) of the 151 isolated strains exhibited antimicrobial activities and inhibited at least one of the indicator strains. Fifty-two strains were selected for further phylogenetic analysis using 16S rRNA gene sequencing, as well as for the presence of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes. These 52 strains belonged to 20 genera from 18 families in 4 phyla, including Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. Five strains with PKS genes and ten strains with NRPS genes were detected. Among them, two strains contained both PKS and NRPS genes. Notoacmeibacter sp. strain HMA008 (class Alphaproteobacteria) exhibited potent antimicrobial activity; thus, whole genome sequencing methods were used to analyse its secondary metabolite biosynthetic gene clusters. The genome of HMA008 contained 12 biosynthetic gene clusters that potentially encode secondary metabolites belonging to compound classes such as non-ribosomal peptides, prodigiosin, terpene, ß-lactones, and siderophore, among others. This study indicates that the sponge Ophlitaspongia sp. harbours diverse bacterial strains with antimicrobial properties and may serve as a potential source of bioactive compounds.

Cd2+ tolerance and removal mechanisms of Serratia marcescens KMR-3.

Heavy metal contamination is a global issue, with cadmium (Cd2+) and its treatment becoming major environmental challenge that could be solved by microbial restoration, an eco-friendly technique. Serratia marcescens KMR-3 exhibits high tolerance and removal rate of Cd2+ (≤500 mg/L). Here, we aimed to explore mechanisms underlying tolerance to and removal of Cd2+ by KMR-3. Scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectrometry were conducted to analyze characteristics of the KMR-3 biofilm and Cd2+ combined forms. The results revealed varying degrees of cell adhesion, membrane thickening, and shrinkage on the surface of the bacteria. The binding elements, electronic binding energy, and functional groups on the surface of the bacteria exhibited changes. Furthermore, the biofilm amount following treatment with Cd2+ was 1.5-3 times higher than that in the controls, treatment with Cd2+ substantially enhanced biofilm generation and increased Cd2+ adsorption. Cd2+ adsorption by its own secondary metabolite prodigiosin produced by KMR-3 was enhanced by 19.5 % compared with that observed without prodigiosin. Through transcriptome sequencing and RT-qPCR, we observed that Znu protein-chelating system regulated gene expression (znuA, znuB, and znuC), and the efflux mechanism of the P-type ATPase regulated the expression of genes (zntA, zntB, and zntR), which were significantly enhanced. Through the combined action of various strategies, KMR-3 demonstrated a high tolerance and removal ability of Cd2+, providing a theoretical basis to treat Cd2+ pollution.

Extracellular lactonase-mediated quorum quenching by a novel Bacillus velezensis.

Many Gram-negative bacteria coordinate their gene expression via quorum sensing (QS) mediated by small diffusible autoinducer molecules such as Acyl Homoserine Lactones (AHL). The degradation of AHLs or quorum quenching (QQ) imparts less selection pressure on the target organisms leading to a possible alternative to antimicrobial agents and traditional biofilm control methods. Here, a novel strain of Bacillus velezensis, strain PM7, exhibiting extracellular QQ activity against Gram-negative bacteria has been isolated. Analytical studies of the AHL degradation using LC-MS as well as bioreporters revealed the mechanism of QQ as homoserine lactone ring hydrolysis. Using molecular techniques, the presence of an aiiA homologues gene, specific for acyl homoserine lactonase enzyme, was confirmed in the bacterium. A biofilm inhibitory activity in the range of 36.9%-77.4% was achieved by the PM7 against three different Gram-negative bacteria. Moreover, a significant reduction (P < .05) in the QS-controlled traits such as violacein production in Chromobacterium violaceum (73%), swarming motility and prodigiosin production (67.2%) in Serratia marcescens, and exopolysaccharide production (97.9%) in Pseudomonas aeruginosa, was also observed. The extracellular and broad-spectrum lactonase of this novel strain can be beneficial for its use in QQ applications.

Mechanisms underlying the inhibitory effects of Cd2+ on prodigiosin synthesis in Serratia marcescens KMR-3.

Prodigiosin (2-methyl-3-pentyl-6-methoxyprodiginine), a red-colored microbial pigment, is produced in large quantities by Serratia marcescens KMR-3. This bacterium can grow in a medium with a Cd2+ concentration of 500 mg/L, but it does not produce prodigiosin when the Cd2+ concentration in the medium is higher than 140 mg/L. Therefore, we investigated the mechanisms by which Cd2+ inhibits prodigiosin synthesis. Upon addition of Cd2+ to the medium, the expression of the prodigiosin (pig) gene cluster was significantly downregulated. Simultaneously, genes encoding proteins related to the synthesis of arginine and proline(prodigiosin precursors) were significantly downregulated, while the degradation-related genes were upregulated. Furthermore, PigF, which encodes a key enzyme involved in the synthesis of 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde and PigC, which encodes a key enzyme involved in the last step of prodigiosin synthesis, were downregulated by 80% and 55%, respectively, following Cd2+ treatment. As PigC and PigF are located on the cell membrane and are involved in the final steps of prodigiosin synthesis, the cell membrane might be presumed to be the site of prodigiosin synthesis. The bacterial membrane exhibited different degrees of elongation, folding, fragmentation, and sagging after the addition of Cd2+, while likely destroying the site of prodigiosin synthesis.

The effectiveness of antimicrobial photodynamic therapy with prodigiosin against reference strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

Prodigiosin (PG) is a secondary metabolite of bacterial origin that is able to absorb the visible light and plays a role as a photosensitizer in photodynamic therapy (PDT). This in vitro study aimed to investigate the cytotoxicity of PG-mediated PDT against the reference strains of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PG were determined. Each strain was then allocated into four groups as follows: G1: control (no treatment), G2: PG-treated groups that received different PG concentrations (1000-1.95 µM), G3: laser-treated group (wavelength: 520 nm, radiation dose: 187 J/cm2), and G4: PG-mediated PDT groups that were initially treated with different concentrations of PG and were then exposed to laser irradiation in the same way as the previous group. Finally, the number of colony-forming units per milliliter (CFU/mL) was calculated and analyzed using the SPSS software. PG had both bacteriostatic and bactericidal activities on the tested bacteria, with the maximum antibacterial effect being observed against S. aureus. In all bacterial strains, the maximum number of CFUs was observed in the control group followed by the laser-irradiated and PG-treated groups, but the differences were not statistically significant (p > 0.05). However, the utilization of PG-mediated PDT resulted in a significant decrease in the mean number of CFUs in all the tested bacteria (p < 0.0001). PG-mediated PDT had the potential to kill some bacterial strains in the laboratory. Yet, further studies are warranted to confirm its efficacy and safety to be applied in clinical settings.

Extraction of the Anticancer and Antimicrobial Agent, Prodigiosin, from Vibrio gazogenes PB1 and Its Identification by 1D and 2D NMR.

Prodigiosin is a secondary metabolite produced in several species of bacteria. It exhibits antimicrobial and anticancer properties. Methods for the extraction and identification of prodigiosin and their related derivatives from bacterial cultures typically depend on solvent-based extractions followed by NMR spectroscopy. The estuarine bacterium, V. gazogenes PB1, was previously shown to produce prodigiosin. This conclusion, however, was based on analytical data obtained from ultraviolet-visible absorption spectrophotometry and infrared spectroscopy. Complete dependence on these techniques would be considered inadequate for the accurate identification of the various members of the prodiginine family of compounds, which possess very similar chemical structures and near-identical optical properties. In this study, we extracted prodigiosin from a culture of Vibrio gazogenes PB1 cultivated in minimal media, and for the first time, confirmed the synthesis of prodigiosin Vibrio gazogenes PB1 using NMR techniques. The chemical structure was validated by 1H and 13C NMR spectroscopy, and further corroborated by 2D NMR, which included 1H-1H-gDQFCOSY, 1H-13C-gHSQC, and 1H-13C-gHMBC, as well as 1H-1H-homonuclear decoupling experiments. Based on this data, previous NMR spectral assignments of prodigiosin are reaffirmed and in some cases, corrected. The findings will be particularly relevant for experimental work relating to the use of V. gazogenes PB1 as a host for the synthesis of prodigiosin.

Concerted regulation of OPG/RANKL/ NF­κB/MMP-13 trajectories contribute to ameliorative capability of prodigiosin and/or low dose γ-radiation against adjuvant- induced arthritis in rats.

BACKGROUND: Prodigiosin (PDG) is a microbial red dye with antioxidant and anti-inflammatory properties, although its effect on rheumatoid arthritis (RA) remains uncertain. Also, multiple doses of low dose γ- radiation (LDR) have been observed to be as a successful intervention for RA. Thus, the purpose of this study was to investigate the ameliorative potential of PDG and/or LDR on adjuvant-induced arthritis (AIA) in rats. METHODS: The anti-inflammatory and anti-arthritic effects of PDG and/or LDR were examined in vitro and in vivo, respectively. In the AIA model, the arthritic indexes, paw swelling degrees, body weight gain, and histopathological assessment in AIA rats were assayed. The impact of PDG (200 µg/kg; p.o) and/or LDR (0.5 Gy) on the levels of pro- and anti-inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-18, IL-17A, and IL-10) as well as the regulation of osteoprotegrin (OPG)/ receptor activator of nuclear factor κB ligand (RANKL)/ nuclear factor-κB (NF-κB)/MMP-13 pathways was determined. Methotrexate (MTX; 0.05 mg/kg; twice/week, i.p) was administered concurrently as a standard anti-arthritic drug. RESULTS: PDG and/or LDR markedly diminished the arthritic indexes, paw edema, weigh loss in AIA rats, alleviated the pathological alterations in joints, reduced the levels of pro-inflammatory cytokines IL-1ß, TNF-α, IL-6, IL-18, IL-17A, and RANKL in serum and synovial tissues, while increasing anti-inflammatory cytokines IL-10 and OPG levels. Moreover, PDG and/or LDR down-regulated the expression of RANKL, NF-κBp65, MMP13, caspase-3, and decreased the RANKL/OPG ratio, whereas OPG and collagen II were enhanced in synovial tissues. CONCLUSION: PDG and/or LDR exhibited obvious anti-RA activity on AIA.

3-Phenylpropan-1-Amine Enhanced Susceptibility of Serratia marcescens to Ofloxacin by Occluding Quorum Sensing.

Serratia marcescens (S. marcescens) is an environmental bacterium that causes infections with high morbidity and mortality. Notably, infections caused by multidrug-resistant S. marcescens have become a global public health issue. Therefore, the discovery of promising compounds to reduce the virulence of pathogens and restore antibiotic activity against multidrug-resistant bacteria is critical. Quorum sensing (QS) regulates virulence factors and biofilm formation of microorganisms to increase their pathogenicity and is, therefore, an important factor in the formation of multidrug resistance. In this study, we found that 3-phenylpropan-1-amine (3-PPA) inhibited S. marcescens NJ01 biofilm formation and virulence factors, including prodigiosin, protease, lipase, hemolysin, and swimming. The combination of 3-PPA (50.0 µg/mL) and ofloxacin (0.2 µg/mL) enhanced S. marcescens NJ01 sensitivity to ofloxacin. Based on crystalline violet staining, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM), 3-PPA (50.0 µg/mL) reduced S. marcescens NJ01 biofilm formation by 48%. Quantitative real-time PCR (qRT-PCR) showed that 3-PPA regulated the expression of virulence- and biofilm-related genes fimA, fimC, bsmB, pigP, flhC, flhD, and sodB. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that 3-PPA affected intracellular metabolites of S. marcescens NJ01, leading to reduce metabolic activity. These results suggested that 3-PPA inhibits the pathogenicity of S. marcescens NJ01 by occluding QS. Thus, 3-PPA is feasible as an ofloxacin adjuvant to overcome multidrug-resistant S. marcescens and improve the treatment of intractable infections. IMPORTANCE Multidrug-resistant bacteria have become a major threat to global public health, leading to increased morbidity, mortality, and health care costs. Bacterial virulence factors and biofilms, which are regulated by quorum sensing (QS), are the primary causes of multidrug resistance. In this study, 3-PPA reduced virulence factors and eliminated biofilm formation by inhibiting QS in S. marcescens NJ01 bacteria, without affecting bacterial growth, thus restoring sensitivity to ofloxacin. Thus, the discovery of compounds that can restore antibiotic activity against bacteria is a promising strategy to mitigate multidrug resistance in pathogens.

Recent Advances in Prodigiosin as a Bioactive Compound in Nanocomposite Applications.

Bionanocomposites based on natural bioactive entities have gained importance due to their abundance; renewable and environmentally benign nature; and outstanding properties with applied perspective. Additionally, their formulation with biological molecules with antimicrobial, antioxidant, and anticancer activities has been produced nowadays. The present review details the state of the art and the importance of this pyrrolic compound produced by microorganisms, with interest towards Serratia marcescens, including production strategies at a laboratory level and scale-up to bioreactors. Promising results of its biological activity have been reported to date, and the advances and applications in bionanocomposites are the most recent strategy to potentiate and to obtain new carriers for the transport and controlled release of prodigiosin. Prodigiosin, a bioactive secondary metabolite, produced by Serratia marcescens, is an effective proapoptotic agent against bacterial and fungal strains as well as cancer cell lines. Furthermore, this molecule presents antioxidant activity, which makes it ideal for treating wounds and promoting the general improvement of the immune system. Likewise, some of the characteristics of prodigiosin, such as hydrophobicity, limit its use for medical and biotechnological applications; however, this can be overcome by using it as a component of a bionanocomposite. This review focuses on the chemistry and the structure of the bionanocomposites currently developed using biorenewable resources. Moreover, the work illuminates recent developments in pyrrole-based bionanocomposites, with special insight to its application in the medical area.

Identifying Algicides of Enterobacter hormaechei F2 for Control of the Harmful Alga Microcystis aeruginosa.

Eutrophication has become an increasingly serious environmental issue and has contributed towards an explosion in harmful algal blooms (HABs) affecting local development. HABs can cause serious threats to ecosystems and human health. A newly isolated algicidal strain, Enterobacter hormaechei F2, showed high algicidal activity against the typical HAB species Microcystis aeruginosa. Potential algicides were detected through liquid chromatograph-mass spectrometer analysis, revealing that prodigiosin is an algicide and PQS is a quorum sensing molecule. RNA-seq was used to understand the algicidal mechanisms and the related pathways. We concluded that the metabolism of prodigiosin and PQS are active at the transcriptional level. The findings indicate that E. hormaechei F2 can be used as a potential biological agent to control harmful algal blooms to prevent the deterioration of the ecological and economic value of water bodies.

Downstream Process Development for Extraction of Prodigiosin: Statistical Optimization, Kinetics, and Biochemical Characterization.

Prodigiosin is natural red colourant derived from Serratia marcescens. However, the high cost of prodigiosin restricts its use in food and pharmaceutical industries, which can be addressed with the design of a suitable extraction procedure. Therefore, the present study aims to use Taguchi methodology to optimize various process parameters during ultrasound-assisted extraction (UAE) to get a higher prodigiosin extraction yield. The most significant contribution comes from the solid-to-liquid ratio (36.66%), followed by sonication of duty cycle (34.82%), medium pH (15.7%), and acoustic intensity (12.82%). The Taguchi technique predicts the highest optimal yield using the solid-liquid ratio (0.3 g/mL), duty cycle sonication (75%), acoustic intensity (12.5 w/cm2), and medium pH (3) as parameters. When the extraction conditions were optimized, the yield of prodigiosin increased by 4166.89 mg/L. In the future, the above extraction conditions determined using Taguchi approach will be applied for large-scale extraction of prodigiosin. Finally, a second-order kinetic model is used to suit the batch extraction investigation and the second-order rate constant (k) has a value of 4 × 10-5 L/mg/min. In the future, the rate constant, which is reported for the first time, will be used to create a batch extractor for commercial extraction of prodigiosin. Prodigiosin has also been shown to have substantial antioxidant and scavenging properties, which increase in a dose-dependent way with prodigiosin concentration. Because of its antioxidant and scavenging properties, prodigiosin can be used as food additives or pharmaceutical ingredients in industries.

Simple Dipyrrin Analogues of Prodigiosin for Use as Colistin Adjuvants.

Multidrug resistant (MDR) bacteria are an increasing public health problem. One promising alternative to the development of new antibiotics is the use of antibiotic adjuvants, which would allow the continued use of FDA-approved antibiotics that have been rendered ineffective due to resistance. Herein, we report a series of dipyrrins and pyrrole derivatives designed as analogues of prodigiosin and obatoclax, several of which potentiate the activity of colistin against Klebsiella pneumoniae, with lead compounds also potentiating colistin against Acinetobacter baumannii and Pseudomonas aeruginosa.