The fsr Quorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16

Dundar, Halil
Brede, Dag A.
La Rosa, Sabina Leanti
El-Gendy, Ahmed Osama
Diep, Dzung B.
Nes, Ingolf F.
A novel antimicrobial peptide designated enterocin O16 was purified from Enterococcus faecalis. Mass spectrometry showed a monoisotopic mass of 7,231 Da, and N-terminal Edman degradation identified a 29-amino-acid sequence corresponding to residues 90 to 119 of the EF_1097 protein. Bioinformatic analysis showed that enterocin O16 is composed of the 68 most C-terminal residues of the EF_1097 protein. Introduction of an in-frame isogenic deletion in the ef1097 gene abolished the production of enterocin O16. Enterocin O16 has a narrow inhibitory spectrum, as it inhibits mostly lactobacilli. Apparently, E. faecalis is intrinsically resistant to the antimicrobial peptide, as no immunity connected to the production of enterocin O16 could be identified. ef1097 has previously been identified as one of three loci regulated by the fsr quorum-sensing system. The introduction of a nonsense mutation into fsrB consistently impaired enterocin O16 production, but externally added gelatinase biosynthesis-activating pheromone restored the antimicrobial activity. Functional genetic analysis showed that the EF_1097 proprotein is processed extracellularly into enterocin O16 by the metalloprotease GelE. Thus, it is evident that the fsr quorum-sensing system constitutes the regulatory unit that controls the expression of the EF_1097 precursor protein and the protease GelE and that the latter is required for the formation of enterocin O16. On the basis of these results, this study identified antibacterial antagonism as a novel aspect related to the function of fsr and provides a rationale for why ef1097 is part of the fsr regulon.


The NF-kappa B target genes ICAM-1 and VCAM-1 are differentially regulated during spontaneous differentiation of Caco-2 cells
Astarci, Erhan; Sade, Asli; Cimen, Ismail; SAVAŞ, BERNA; Banerjee, Sreeparna (Wiley, 2012-08-01)
Intestinal epithelial differentiation entails the formation of highly specialized cells with specific absorptive, secretory, digestive and immune functions. Cellcell and cellmicroenvironment interactions appear to be crucial in determining the outcome of the differentiation process. Using the Caco-2 cell line, which undergoes spontaneous re-differentiation when grown past confluency, we observed a loss of VCAM-1 (vascular cell adhesion molecule 1) mRNA expression, while ICAM-1 (intercellular cell adhesion m...
Structural Insights into Alternate Aggregated Prion Protein Forms
POLANO, maurizio; Bek, Alpan; BENETTİ, federico; lazzarino, marco; LEGNAME, giuseppe (Elsevier BV, 2009-11-13)
The conversion of the cellular form of the prion protein (PrPC) to an abnormal, alternatively folded isoform (PrPSc) is the central event in prion diseases or transmissible spongiform encephalopathies. Recent studies have demonstrated de novo generation of murine prions from recombinant prion protein (recPrP) after inoculation into transgenic and wild-type mice. These so-called synthetic prions lead to novel prion diseases with unique neuropathological and biochemical features. Moreover, the use of recPrP i...
Investigation of cytocidal effect of K5 type yeast killer protein on sensitive microbial cells
Sertkaya, Abdullah; İzgü, Kadri Fatih; Department of Biology (2005)
Some yeasts secrete polypeptide toxins, which are lethal to other sensitive yeast cells, gram-positive pathogenic bacteria and pathogenic fungi. Therefore these are designated as killer toxins. Killer toxins are suggested as potent antimicrobial agents especially for the protection of fermentation process against contaminating yeasts, biological control of undesirable yeasts in the preservation of foods. Moreover they are promising antimicrobial agents in the medical field; due to immune system suppressing ...
Cloning, characterization and heterologous expression of the aspartokinase and aspartate semialdehyde dehydrogenase genes of cephamycin C-producer Streptomyces clavuligerus
Tunca, S; Yilmaz, EI; Piret, J; Liras, P; Özcengiz, Gülay (Elsevier BV, 2004-09-01)
Carbon flow through the lysine branch of the aspartate biosynthetic pathway is a rate-limiting step in the formation of cephamycin C, a broad spectrum P-lactam antibiotic produced by Streptomyces clavuligerus. In this study, genes which encode the enzymes catalyzing the first two steps of the aspartate pathway, ask (aspartokinase) and asd (aspartate semialdehyde dehydrogenase), in S. clavuligerus NRRL 3585 were cloned and sequenced. Nucleotide sequencing and codon preference analysis revealed three complete...
Targeted disruption of homoserine dehydrogenase gene in Streptomyces clavuligerus and its effects on cephamycin C production
Çaydaşı (Koca), Ayşe; Özcengiz, Gülay; Department of Biology (2006)
The members of the genus Streptomyces are well-known for their capacity to synthesize a vast repertoire of secondary metabolites, including many useful antibiotics and proteins. Streptomyces clavuligerus is the producer of the medically important β-lactam antibiotics such as cephamycin C and the potent β-lactamase inhibitor clavulanic acid. The aspartate pathway of S. clavuligerus is an important primary metabolic pathway providing substrates for β-lactam synthesis. This pathway uses L-aspartic acid as the ...
Citation Formats
H. Dundar, D. A. Brede, S. L. La Rosa, A. O. El-Gendy, D. B. Diep, and I. F. Nes, “The fsr Quorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16,” JOURNAL OF BACTERIOLOGY, pp. 2112–2121, 2015, Accessed: 00, 2020. [Online]. Available: