Biosynthesis of the acetyl‐CoA carboxylase‐inhibiting antibiotic, andrimid in Serratia is regulated by Hfq and the LysR‐type transcriptional regulator, AdmX

Abstract

SummaryInfections due to multidrug‐resistant bacteria represent a major global health challenge. To combat this problem, new antibiotics are urgently needed and some plant‐associated bacteria are a promising source. The rhizobacterium Serratia plymuthica A153 produces several bioactive secondary metabolites, including the anti‐oomycete and antifungal haterumalide, oocydin A and the broad spectrum polyamine antibiotic, zeamine. In this study, we show that A153 produces a second broad spectrum antibiotic, andrimid. Using genome sequencing, comparative genomics and mutagenesis, we defined new genes involved in andrimid (adm) biosynthesis. Both the expression of the adm gene cluster and regulation of andrimid synthesis were investigated. The biosynthetic cluster is operonic and its expression is modulated by various environmental cues, including temperature and carbon source. Analysis of the genome context of the adm operon revealed a gene encoding a predicted LysR‐type regulator, AdmX, apparently unique to Serratia strains. Mutagenesis and gene expression assays demonstrated that AdmX is a transcriptional activator of the adm gene cluster. At the post‐transcriptional level, the expression of the adm cluster is positively regulated by the RNA chaperone, Hfq, in an RpoS‐independent manner. Our results highlight the complexity of andrimid biosynthesis – an antibiotic with potential clinical and agricultural utility.

Growth on Chitin Impacts the Transcriptome and Metabolite Profiles of Antibiotic-Producing Vibrio coralliilyticus S2052 and Photobacterium galatheae S2753

“…We speculate that the well-known antibacterial compounds holomycin (34) and andrimid (35) may serve to antagonize competitors and that the quorum-sensing-interfering molecules solonamides and ngercheumicins may be involved in intercellular communication since they can interfere with the quorum-sensing system of Staphylococcus aureus (36, 37); however, the elucidation of the exact function of the secondary metabolites identified in this work during chitin colonization requires further work. With regard to the transcriptional regulation of the biosynthesis of secondary metabolites, the upregulation of the andrimid biosynthetic genes and of the LysR family transcriptional regulator located just downstream of them supports the hypothesis that such a regulator may have an important regulatory role in andrimid biosynthesis (38). Similarly, the downregulation of the ArsR family transcriptional regulator gene located upstream of the holomycin biosynthetic genes may indicate a role of the encoded regulator as a repressor of holomycin production.…”

Genome Sequence of Serratia marcescens MSU97, a Plant-Associated Bacterium That Makes Multiple Antibiotics

“…MSU97 was the most abundant isolated bacterium found in healthy R. pedicillata plants, and this plant protection phenotype was associated with its ability to inhibit the growth of plant-pathogenic oomycetes, fungi, and bacteria (4, 7, 8). Thus, the strain synthesizes various secondary metabolites, including the antibacterial compound andrimid (8), the antifungal and antioomycete haterumalide oocydin A (7, 9), and the red tripyrrole antibiotic prodigiosin (4). MSU97 was also shown to be highly virulent in Caenorhabditis elegans infection models (7).…”

Genome Sequence of Serratia plymuthica A153, a Model Rhizobacterium for the Investigation of the Synthesis and Regulation of Haterumalides, Zeamine, and Andrimid

“…Serratia plymuthica A153 was isolated from the rhizosphere of wheat ( 3 ) and synthesizes multiple bioactive secondary metabolites, including several antifungal, antioomycete, and anticancer haterumalides/oocydins ( 4 ), the bacterial acetyl-CoA carboxylase inhibitor andrimid ( 5 ), the polyamino antibiotic zeamine ( 6 ), and the broad spectrum antifungal compound pyrrolnitrin ( 4 ). Serratia plymuthica A153 was used to identify the biosynthetic cluster encoding synthesis of the haterumalide oocydin A ( 7 ).…”

“…Serratia plymuthica A153 was used to identify the biosynthetic cluster encoding synthesis of the haterumalide oocydin A ( 7 ). Furthermore, it was used as a model bacterium for the study of the regulation of multiple bioactive non-ribosomal peptides and polyketides ( 5 , 6 , 8 )—research which was greatly facilitated by the facile genetic tractability of A153 and the isolation of a highly efficient generalized transducing phage, ϕMAM1 ( 9 ).…”