Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules

Abstract

Prodigiosin is a heterocyclic bacterial secondary metabolite belonging to the class of tripyrrole compounds, synthesized by various types of bacteria including Serratia species. Prodigiosin has been the subject of intense research over the last decade for its ability to induce apoptosis in several cancer cell lines. Reports suggest that prodigiosin promotes oxidative damage to double-stranded DNA (dsDNA) in the presence of copper ions and consequently leads to inhibition of cell-cycle progression and cell death. However, prodigiosin has not been previously implicated in biofilm inhibition. In this study, the link between prodigiosin and biofilm inhibition through the production of redox active metabolites is presented. Our study showed that prodigiosin (500 μM) (extracted from Serratia marcescens culture) and a prodigiosin/copper(II) (100 μM each) complex have strong RNA and dsDNA cleaving properties while they have no pronounced effect on protein. Results support a role for oxidative damage to biomolecules by H2O2 and hydroxyl radical generation. Further, it was demonstrated that reactive oxygen species scavengers significantly reduced the DNA and RNA cleaving property of prodigiosin. P. aeruginosa cell surface hydrophobicity and biofilm integrity were significantly altered due to the cleavage of nucleic acids by prodigiosin or the prodigiosin/copper(II) complex. In addition, prodigiosin also facilitated the bactericidal activity. The ability of prodigiosinto cause nucleic acid degradation offers novel opportunities to interfere with extracellular DNA dependent bacterial biofilms.

Natural Compounds from Herbs that can Potentially Execute as Autophagy Inducers for Cancer Therapy

“…The biological role of these pigments in the producer organisms remains unclear. Bacterial PGs and their synthetic derivatives have antimicrobial (bactericidal and bacteriostatic) [ 109 , 110 , 111 , 112 ], antimalarial [ 109 , 110 , 113 ], and antitumor [ 109 , 110 , 114 , 115 , 116 ] activities. In addition, they have been shown to be effective apoptotic agents against various cancer cell lines [ 117 ], with multiple cellular targets including multi-drug resistant cells with little or no toxicity towards normal cell lines and induce apoptosis in T and B lymphocytes [ 118 , 119 ].…”

PG-Priming Enhances Doxorubicin Influx to Trigger Necrotic and Autophagic Cell Death in Oral Squamous Cell Carcinoma

“…Prodigiosin (PG, PubChem CID: 5351169) is a red prodiginine pigment isolated from various bacteria including Serratia marcescens, Pseudoalteromonas rubra, Hahella chejuensis, and actinomycete bacteria [ 22 , 23 , 24 , 25 ]. Even though the original biological function in producer bacteria remains unclear, PG has been identified with numerous biological activities including antimicrobial [ 26 , 27 , 28 , 29 ], antimalarial [ 26 , 27 , 30 ], and antitumor [ 26 , 27 , 31 , 32 , 33 , 34 ] activities. Moreover, PG showed apoptotic inducing property in many cancer types such as lung cancer [ 35 , 36 , 37 ], breast cancer [ 38 , 39 ], colorectal cancer [ 40 , 41 , 42 ], leukemia [ 43 , 44 ], and hepatocellular carcinoma [ 45 ] without normal cell cytotoxicity [ 41 , 46 ].…”

Pseudomonas aeruginosa Extracellular Secreted Molecules Have a Dominant Role in Biofilm Development and Bacterial Virulence in Cystic Fibrosis Lung Infections

“…A recent study by Kimyon et al showed that prodigiosin (a heterocyclic bacterial secondary metabolite secreted by Serratia sp.) induces biofilm disruption and exhibits bactericidal activity against P. aeruginosa [98]. Prodigiosin-mediated P. aeruginosa biofilm disruption occurs by the release of H 2 O 2 and generation of hydroxyl radicals in the presence of copper ions that consequently cleaves/damages eDNA and alters P. aeruginosa cell surface hydrophobicity.…”

“…Prodigiosin-mediated P. aeruginosa biofilm disruption occurs by the release of H 2 O 2 and generation of hydroxyl radicals in the presence of copper ions that consequently cleaves/damages eDNA and alters P. aeruginosa cell surface hydrophobicity. Prodigiosin also induces bacterial cell lysis as a consequence of the oxidative stress generated by H 2 O 2 [98].…”