Identification of a methicillin-resistant Staphylococcus aureus inhibitory compound isolated from Serratia marcescens

Kadouri, Daniel E.; Shanks, Robert M. Q.

doi:10.1016/j.resmic.2013.06.002

Cited by 31 publications

(24 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…; Romero‐Tabarez et al . ; Kadouri and Shanks ). These findings suggest that screening cell‐free extracts may be a useful method for isolating antimicrobial compounds from environmental bacteria.…”

Section: Discussionmentioning

confidence: 99%

Environmental bacteria produce abundant and diverse antibiofilm compounds

et al. 2014

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Environmental bacteria produce abundant and diverse antibiofilm compounds

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Other transposon-based genetic screens that provided impetus to analyze these two ORFs included the following: (i) a mutation in SMDB11_3959 eliminated production of an antistaphylococcal compound produced by S. marcescens (15), (ii) multiple mutations of SMDB11_3958 eliminated secreted hemolysis activity by a clinical isolate, K904, and (iii) a mutation upstream of SMDB11_3959 eliminated protease secretion by a nonpigmented ocular clinical isolate, K949 (data not shown). Altogether, 12 independent mutations in SMDB11_3958 and SMDB11_3959 have been identified, and all of these mutant strains were found to be deficient in hemolysis (serratamolide) and, if the strain was pigmented, defective in prodigiosin production.…”

Section: Identification Of Eepr and Eepsmentioning

confidence: 99%

“…The chromosomal prodigiosin biosynthetic operon was placed under the control of an arabinose-inducible promoter through integration of pMQ262 (15) in the ⌬eepR strain (CMS2097) to test whether expression of pigA-N alone is sufficient to restore prodigiosin production. Red pigment production was restored when the strain was grown with the addition of the inducer L-arabinose but not when treated with glucose or water (Fig.…”

Section: Identification Of Eepr and Eepsmentioning

confidence: 99%

See 1 more Smart Citation

Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites

et al. 2015

View full text Add to dashboard Cite

Serratia marcescens generates secondary metabolites and secreted enzymes, and it causes hospital infections and communityacquired ocular infections. Previous studies identified cyclic AMP (cAMP) receptor protein (CRP) as an indirect inhibitor of antimicrobial secondary metabolites. Here, we identified a putative two-component regulator that suppressed crp mutant phenotypes. Evidence supports that the putative response regulator eepR was directly transcriptionally inhibited by cAMP-CRP. EepR and the putative sensor kinase EepS were necessary for the biosynthesis of secondary metabolites, including prodigiosin-and serratamolide-dependent phenotypes, swarming motility, and hemolysis. Recombinant EepR bound to the prodigiosin and serratamolide promoters in vitro. Together, these data introduce a novel regulator of secondary metabolites that directly connects the broadly conserved metabolism regulator CRP with biosynthetic genes that may contribute to competition with other microbes. IMPORTANCEThis study identifies a new transcription factor that is directly controlled by a broadly conserved transcription factor, CRP. CRP is well studied in its role to help bacteria respond to the amount of nutrients in their environment. The new transcription factor EepR is essential for the bacterium Serratia marcescens to produce two biologically active compounds, prodigiosin and serratamolide. These two compounds are antimicrobial and may allow S. marcescens to compete for limited nutrients with other microorganisms. Results from this study tie together the CRP environmental nutrient sensor with a new regulator of antimicrobial compounds. Beyond microbial ecology, prodigiosin and serratamolide have therapeutic potential; therefore, understanding their regulation is important for both applied and basic science. In order for organisms to survive and prosper, they must be able to sense their environment and effectively compete with other organisms. To respond to these environmental changes, bacteria have developed elaborate transcriptional regulatory systems that enable fine-tuning of factors that allow for their adaptation and proliferation. One of the most studied signaling systems involved in adaptation to the nutritive status of the environment is the cyclic AMP (cAMP)-associated catabolite repression system (1-4). The second messenger cAMP has been classified as an alarmone that induces positive regulation of alternative carbon transport systems in times of carbon/fuel deprivation (5). In addition to catabolite repression control, this system also can positively regulate flagellum production in unfavorable conditions (6) and activate attachment factors in nutrient-rich conditions (7).Evidence suggests that cAMP-cAMP receptor protein (CRP) can directly bind to and promote expression of secondary metabolite genes involved in antibiotic production in Streptomyces coelicolor (2). A positive or negative role for cAMP has been suggested for control of antimicrobial production in other organisms, including fungi, although dire...

show abstract

“…marcescens ATCC 274 has been shown to have antimicrobial properties against meticillin-resistant Sta. aureus (MRSA) (Kadouri & Shanks, 2013). In Ser.…”

Section: Resultsmentioning

confidence: 99%

Role of the phosphopantetheinyltransferase enzyme, PswP, in the biosynthesis of antimicrobial secondary metabolites by Serratia marcescens Db10

2014

View full text Add to dashboard Cite

Phosphopantetheinyltransferase (PPTase) enzymes fulfil essential roles in primary and secondary metabolism in prokaryotes, archaea and eukaryotes. PPTase enzymes catalyse the essential modification of the carrier protein domain of fatty acid synthases, polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs). In bacteria and fungi, NRPS and PKS enzymes are often responsible for the biosynthesis of secondary metabolites with clinically relevant properties; these secondary metabolites include a variety of antimicrobial peptides. We have previously shown that in the Gram-negative bacterium Serratia marcescens Db10, the PPTase enzyme PswP is essential for the biosynthesis of an NRPS-PKS dependent antibiotic called althiomycin. In this work we utilize bioinformatic analyses to classify PswP as belonging to the F/KES subfamily of Sfp type PPTases and to putatively identify additional NRPS substrates of PswP, in addition to the althiomycin NRPS-PKS, in Ser. marcescens Db10. We show that PswP is required for the production of three diffusible metabolites by this organism, each possessing antimicrobial activity against Staphylococcus aureus. Genetic analyses identify the three metabolites as althiomycin, serrawettin W2 and an as-yet-uncharacterized siderophore, which may be related to enterobactin. Our results highlight the use of an individual PPTase enzyme in multiple biosynthetic pathways, each contributing to the ability of Ser. marcescens to inhibit competitor bacteria by the production of antimicrobial secondary metabolites.

show abstract

Identification of a methicillin-resistant Staphylococcus aureus inhibitory compound isolated from Serratia marcescens

Cited by 31 publications

References 21 publications

Environmental bacteria produce abundant and diverse antibiofilm compounds

Environmental bacteria produce abundant and diverse antibiofilm compounds

Serratia marcescens Cyclic AMP Receptor Protein Controls Transcription of EepR, a Novel Regulator of Antimicrobial Secondary Metabolites

Role of the phosphopantetheinyltransferase enzyme, PswP, in the biosynthesis of antimicrobial secondary metabolites by Serratia marcescens Db10

Contact Info

Product

Resources

About