Regulator RcsB Controls Prodigiosin Synthesis and Various Cellular Processes in Serratia marcescens JNB5-1

Abstract

Prodigiosin, a red linear tripyrrole pigment normally secreted by Serratia marcescens, has received attention for its reported immunosuppressive, antimicrobial and anticancer properties. Although several genes have been shown to be important for prodigiosin synthesis, information on the regulatory mechanisms behind this cellular process remains limited. In this work, we identified that the transcriptional regulator RcsB encoding gene BVG90_13250 (rcsB) negatively controlled prodigiosin biosynthesis in S. marcescens. Disruption of rcsB conferred a remarkably increased production of prodigiosin. This phenotype corresponded to RcsB negative control of transcription of the prodigiosin-associated pig operon probably by binding to the promoter region of the prodigiosin synthesis positive regulator FlhDC. Moreover, using transcriptomics and further experiments, we revealed that RcsB also controlled some other important cellular processes, including swimming and swarming motilities, capsular polysaccharide production, biofilm formation, and acid resistance in S. marcescens. Collectively, this work proposes that RcsB is a prodigiosin synthesis repressor in S. marcescens and provides insight into the regulatory mechanism of RcsB on cell motility, capsular polysaccharide production, and acid resistance in S. marcescens. Importance RcsB is a two-component response regulator in the Rcs phosphorelay system, and plays versatile regulatory functions in Enterobacteriaceae. However, information on the function of the RcsB protein in bacteria, especially in S. marcescens remains limited. In this work, we illustrated experimentally that the RcsB protein was involved in diverse cellular processes in S. marcescens, including prodigiosin synthesis, cell motility, capsular polysaccharide production, biofilm formation, and acid resistance. Additionally, the regulatory mechanism of the RcsB protein on these cellular processes was investigated. In conclusion, this work indicated that RcsB could be a regulator for prodigiosin synthesis and provides insight into the function of RcsB protein in S. marcescens.

Identification of Essential Genes Associated With Prodigiosin Production in Serratia marcescens FZSF02

“…More details on the regulation of prodigiosin by slyA are still unknown. RcsA was a positive regulatory gene of prodigiosin production in this study, which was accordance with the recent study in S. marcescens JNB5-1 (Pan et al, 2021). Some mutants with genes encoding membrane proteins inserted showed significantly decreased prodigiosin production.…”

PsrA is a novel regulator contributes to antibiotic synthesis, bacterial virulence, cell motility and extracellular polysaccharides production in Serratia marcescens

“…S. marcescens , a part of the Enterobacteriaceae family of eubacteria, is found in a wide range of ecological niches and can produce many high-value secondary metabolites like prodigiosin ( 1 ), althiomycin ( 2 ), serratamolide ( 3 ). Besides the well-studied bacterial genes involved in the metabolic pathway of the secondary metabolites, a number of transcriptional regulator-encoding genes that play important roles in secondary metabolites synthesis in S. marcescens have also been investigated, such as regulator MetR ( 10 ), SpnR ( 11 ), CopA ( 12 ), CRP ( 13 ), HexS ( 14 ), RssB ( 15 ), RcsB ( 16 , 17 ), SmaR ( 18 ), EepR ( 6 ), PigP ( 7 ), GumB ( 8 ), RbsR ( 9 ), and RpoS ( 61 ) mediates prodigiosin production and regulator GumB ( 8 ), EepR ( 6 , 34 ), PigP ( 62 ) and HexS ( 7 ) regulation of serratamolide synthesis. However, our understanding of the regulatory mechanisms behind secondary metabolites synthesis in S. marcescens is still limited.…”

“…Previous studies on the metabolic regulation network of prodigiosin biosynthesis in S. marcescens have revealed that pigABCDEFGHIJKLMN genes were involved in the biosynthetic pathway of prodigiosin synthesis ( Supplementary Figure S1 ) ( 1 ). Also, it is reported that prodigiosin biosynthesis in S. marcescens was widely regulated by a number of transcription factors including positive regulators EepR ( 6 ), PigP ( 7 ), GumB ( 8 ) and RbsR ( 9 ), and negative regulators MetR ( 10 ), SpnR ( 11 ), CopA ( 12 ), CRP ( 13 ), HexS ( 14 ), RssB ( 15 ), RcsB ( 16 , 17 ) and SmaR ( 18 ).…”

Fnr Negatively Regulates Prodigiosin Synthesis in Serratia sp. ATCC 39006 During Aerobic Fermentation

“…Motility bioassays were performed as described by Fineran et al (2005b) and Pan et al (2021), with slight modifications. Overnight cultured Serratia sp.…”