Prodigiosin found in Serratia marcescens y2 initiates phototoxicity in the cytomembrane

Wang, Fei; Luo, Hailan; Song, Guohua; Liu, Chang; Wang, Jianguo; Xu, Steven Jing-Liang; Su, Xiuhong; Xu, Yangsheng

doi:10.2225/vol16-issue4-fulltext-7

Cited by 18 publications

(12 citation statements)

References 27 publications

(24 reference statements)

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“…The pigment and the cellular membrane were attacked by reactive oxygen. Subsequent lipid peroxidation damaged the integrity of the cellular membrane (Wang et al 2013 )that could be clearly observed in the SEM (Fig. 4 a, b).…”

Section: Discussionmentioning

confidence: 89%

Prodigiosin inhibits motility and activates bacterial cell death revealing molecular biomarkers of programmed cell death

Darshan

Manonmani

2016

AMB Expr

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The antimicrobial activity of prodigiosin from Serratia nematodiphila darsh1, a bacterial pigment was tested against few food borne bacterial pathogens Bacillus cereus, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. The mode of action of prodigiosin was studied. Prodigiosin induced bactericidal activity indicating a stereotypical set of biochemical and morphological feature of Programmed cell death (PCD). PCD involves DNA fragmentation, generation of ROS, and expression of a protein with caspase-like substrate specificity in bacterial cells. Prodigiosin was observed to be internalized into bacterial cells and was localized predominantly in the membrane and the nuclear fraction, thus, facilitating intracellular trafficking and then binding of prodigiosin to the bacterial DNA. Corresponding to an increasing concentration of prodigiosin, the level of certain proteases were observed to increase in bacteria studied, thus initiating the onset of PCD. Prodigiosin at a sub-inhibitory concentration inhibits motility of pathogens. Our observations indicated that prodigiosin could be a promising antibacterial agent and could be used in the prevention of bacterial infections.

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Section: Discussionmentioning

confidence: 89%

Prodigiosin inhibits motility and activates bacterial cell death revealing molecular biomarkers of programmed cell death

Darshan

Manonmani

2016

AMB Expr

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“…Samples were filtered through a 0.45-μm pore size membrane (Merck-Millipore, Billerica, MA, USA), and then quantified by HPLC (Shimadzu, Kyoto, Japan) with a UV detector (535 nm). Aliquots were analyzed by isocratic elution in a solution of 10% 0.5 M PBS, 75% methanol, and 15% water on a C-8 Eclipse XDB column (5 µm, 4.6 × 150 mm; Agilent, USA) with a flow rate of 0.8 mL/min at 30 °C [ 57 ].…”

Section: Methodsmentioning

confidence: 99%

The metabolic switch can be activated in a recombinant strain of Streptomyces lividans by a low oxygen transfer rate in shake flasks

et al. 2018

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BackgroundIn Streptomyces, understanding the switch from primary to secondary metabolism is important for maximizing the production of secondary metabolites such as antibiotics, as well as for optimizing recombinant glycoprotein production. Differences in Streptomyces lividans bacterial aggregation as well as recombinant glycoprotein production and O-mannosylation have been reported due to modifications in the shake flask design. We hypothetized that such differences are related to the metabolic switch that occurs under oxygen-limiting conditions in the cultures.ResultsShake flask design was found to affect undecylprodigiosin (RED, a marker of secondary metabolism) production; the RED yield was 12 and 385 times greater in conventional normal Erlenmeyer flasks (NF) than in baffled flasks (BF) and coiled flasks (CF), respectively. In addition, oxygen transfer rates (OTR) and carbon dioxide transfer rates were almost 15 times greater in cultures in CF and BF as compared with those in NF. Based on these data, we obtained respiration quotients (RQ) consistent with aerobic metabolism for CF and BF, but an RQ suggestive of anaerobic metabolism for NF.ConclusionAlthough the metabolic switch is usually related to limitations in phosphate and nitrogen in Streptomyces sp., our results reveal that it can also be activated by low OTR, dramatically affecting recombinant glycoprotein production and O-mannosylation and increasing RED synthesis in the process.Electronic supplementary materialThe online version of this article (10.1186/s12934-018-1035-3) contains supplementary material, which is available to authorized users.

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“…Prodigiosin, which is produced from the precursors 2-octenal and proline in a complex bifurcated pathway, has several relevant properties such as immunosuppressive and anticancer activities toward different types of human cancer cells [ 9 – 11 ], as well as antimicrobial effects against Gram-positive and Gram-negative bacteria [ 12 – 15 ]. Several molecular mechanisms causing the antibiotic effects of prodigiosin are currently discussed, e.g., membrane potential alteration via anion symport [ 16 ], membrane damage [ 15 ], phototoxicity [ 17 ], and formation of reactive oxygen species (ROS) [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Natural biocide cocktails: Combinatorial antibiotic effects of prodigiosin and biosurfactants

et al. 2018

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Bacterial secondary metabolites are naturally produced to prevail amongst competitors in a shared habitat and thus represent a valuable source for antibiotic discovery. The transformation of newly discovered antibiotic compounds into effective drugs often requires additional surfactant components for drug formulation. Nature may also provide blueprints in this respect: A cocktail of two compounds consisting of the antibacterial red pigment prodigiosin and the biosurfactant serrawettin W1 is naturally produced by the bacterium Serratia marcescens, which occurs in highly competitive habitats including soil. We show here a combinatorial antibacterial effect of these compounds, but also of prodigiosin mixed with other (bio)surfactants, against the soil-dwelling bacterium Corynebacterium glutamicum taken as a model target bacterium. Prodigiosin exerted a combinatorial inhibitory effect with all tested surfactants in a disk diffusion assay which was especially pronounced in combination with N-myristoyltyrosine. Minimal inhibitory and bactericidal concentrations (MIC and MBC) of the individual compounds were 2.56 μg/mL prodigiosin and 32 μg/mL N-myristoyltyrosine, and the MIC of prodigiosin was decreased by 3 orders of magnitude to 0.005 μg/mL in the presence of 16 μg/mL N-myristoyltyrosine, indicative of synergistic interaction. Investigation of bacterial survival revealed similar combinatorial effects; moreover, antagonistic effects were observed at higher compound concentrations. Finally, the investigation of microcolony formation under combined application of concentrations just below the MBC revealed heterogeneity of responses with cell death or delayed growth. In summary, this study describes the combinatorial antibacterial effects of microbial biomolecules, which may have ecological relevance by inhibiting cohabiting species, but shall furthermore inspire drug development in the combat of infectious disease.

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Prodigiosin found in Serratia marcescens y2 initiates phototoxicity in the cytomembrane

Cited by 18 publications

References 27 publications

Prodigiosin inhibits motility and activates bacterial cell death revealing molecular biomarkers of programmed cell death

Prodigiosin inhibits motility and activates bacterial cell death revealing molecular biomarkers of programmed cell death

The metabolic switch can be activated in a recombinant strain of Streptomyces lividans by a low oxygen transfer rate in shake flasks

Natural biocide cocktails: Combinatorial antibiotic effects of prodigiosin and biosurfactants

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