Advances in Characterizing the Transport Systems of and Resistance to EntDD14, A Leaderless Two-Peptide Bacteriocin with Potent Inhibitory Activity

Pérez-Ramos, Adrián; Ladjouzi, Rabia; Mihășan, Marius; Teiar, Radja; Benachour, Abdellah; Drider, Djamel

doi:10.3390/ijms24021517

Cited by 5 publications

(10 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The functions of the ddC and ddD genes products are unknown and could serve in the bacteriocin self-immunity. The ddE and ddF encode an essential channel constituted by DdE and DdF, which serves to translocate EntDD14 outside of the cytoplasm 32,33 . Finally, ddGHIJ encode for an ABC transporter composed of the DdG, DdH, DdI, and DdJ proteins contributing to EntDD14 translocation and to resistance to this bacteriocin when it is externally supplied 32,34, .…”

Section: Discussionmentioning

confidence: 99%

Lack of Polynucleotide Phosphorylase activity in Enterococcus faecalis 14 increases the stability of EntDD14 bacteriocin transcripts

Ladjouzi

Lucau-Danila

López

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

A mutant deficient in polynucleotide phosphorylase (PNPase) activity was previously constructed in Enterococcus faecalis 14; a strain producing a leaderless two-peptide bacteriocin, named enterocin DD14 (EntDD14). Here, we examined the impact of the absence of PNPase on the expression and synthesis of EntDD14, at the transcriptional and functional levels. Consequently, synthesis of EntDD14 started after only 3 h of growth at 37ºC and reached its highest level after 9 h, in both E. faecalis 14 and its isogenic PNPase deficient (ΔpnpA), and has remarkably increased at least two-fold in the ΔpnpA mutant. Notably, high expression level of the ddABCDEFGHIJ cluster was registered in ΔpnpA mutant. Transcriptional and in silico analyses support the existence of ddAB and ddCDEFGHIJ independent transcripts, and analysis of the fate of ddAB and ddCDEFGHIJ mRNAs indicated that the differences in mRNA levels and the high EntDD14 activity are likely due to a better stability of the two transcripts in the ΔpnpA mutant, which should result in a higher translation efficiency of the ddAB EntDD14 structural genes and their other protein determinants. Consequently, this study shows a potential link between the mRNA stability and EntDD14 synthesis, secretion and immunity in a genetic background lacking PNPase.

show abstract

Section: Discussionmentioning

confidence: 99%

Lack of Polynucleotide Phosphorylase activity in Enterococcus faecalis 14 increases the stability of EntDD14 bacteriocin transcripts

Ladjouzi

Lucau-Danila

López

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…The best-known immunity system reported for LLBs is the ABC-type multi-drug resistance transporter protein. This ABC transporter was reported for many bacteriocins, including LLB (Figure 5), to be cyclic and non-leaderless [15,22,40,53,59]. This transporter was thought to play a role in both transport and immunity.…”

Section: The Synthesis and Genetic Organization Of The Leaderless Bac...mentioning

confidence: 94%

“…Clusters of some representative LLBs are depicted in Figure 5. Next, studies performed on aureocin A53 [46] lacticin Q or lacticin Z [47][48][49], aureocin A70 [39,50], and EntDD14 [51][52][53] permitted to gain insights into their genetic organization and genes associated functions. Nevertheless, the mechanisms involved in their immunity and transport outside the bacteriocinogenic strains remain to be understood.…”

Section: The Synthesis and Genetic Organization Of The Leaderless Bac...mentioning

confidence: 99%

“…These bacterial ABC transporters are composed of an ATP-binding protein and often one or more accessory proteins [63]. The deficiency of one more component of this ABC transporter affects the self-immunity system of the producing strains [21,53,64]. The transport of bacteriocins is most often mediated by an ABC transporter system [65] or in some cases by a secretory pathway [65].…”

Section: The Synthesis and Genetic Organization Of The Leaderless Bac...mentioning

confidence: 99%

See 1 more Smart Citation

A Review on Enterocin DD14, the Leaderless Two-Peptide Bacteriocin with Multiple Biological Functions and Unusual Transport Pathway

et al. 2023

Self Cite

View full text Add to dashboard Cite

Enterocin DD14 (EntDD14) is a two-peptide leaderless bacteriocin (LLB) produced by Enterococcus faecalis 14, a human strain isolated from meconium. Studies performed on EntDD14 enabled it to show its activity against Gram-positive bacteria such as Listeria monocytogenes, Clostridium perfringens, Enterococcus faecalis, and Staphylococcus aureus. EntDD14 was also shown to potentiate the activity of different antibiotics such as erythromycin, kanamycin, and methicillin when assessed against methicillin-resistant Staphylococcus aureus (MRSA) in vitro and in vivo in the NMRI-F holoxenic mouse model. Additionally, EntDD14 has an antiviral activity and decreased the secretion of pro-inflammatory IL-6 and IL-8 in inflamed human intestinal Caco-2 cells. The genome of E. faecalis 14 was sequenced and annotated. Molecular tools such as Bagel4 software enabled us to locate a 6.7kb-EntDD14 cluster. Transport of EntDD14 outside of the cytoplasm was shown to be performed synergistically by a channel composed of two pleckstrin-homology-domain-containing proteins, namely DdE/DdF and the ABC transporter DdGHIJ. This latter could also protect the bacteriocinogenic strain against extracellular EntDD14. Here, we focus on academic data and potential therapeutic issues of EntDD14, as a model of two-peptide LLB.

show abstract

“…Periplasmic binding proteins are needed in some cases to confer affinity, specificity, and directionality to the ABC transporter, as well as peripheral or auxiliary proteins [ 26 ]. In the case of the ABC transporter shared by both gene clusters, recent studies on EntDD14, a L50-like leaderless enterocin, have described a dual role for this transporter, which is involved in both self-immunity and export of the enterocin [ 27 ]. However, knowledge on the role of each individual component remans limited.…”

Section: Introductionmentioning

confidence: 99%

Circular and L50-like leaderless enterocins share a common ABC-transporter immunity gene

Teso-Pérez,

Martínez-Bueno,

Peralta Sánchez

et al. 2023

BMC Genomics

View full text Add to dashboard Cite

Microbes live within complex communities of interacting populations, either free-living in waters and soils or symbionts of animals and plants. Their interactions include the production of antimicrobial peptides (bacteriocins) to antagonize competitors, and these producers must carry their own immunity gene for self-protection. Whether other coexisting populations are sensitive or resistant to the bacteriocin producer will be key for the population dynamics within the microbial community. The immunity gene frequently consists of an ABC transporter to repel its own bacteriocin but rarely protects against a nonrelated bacteriocin. A case where this cross-resistance occurs mediated by a shared ABC transporter has been shown between enterocins MR10A/B and AS-48. The first is an L50-like leaderless enterocin, while AS-48 is a circular enterocin. In addition, L50-like enterocins such as MR10A/B have been found in E. faecalis and E. faecium, but AS-48 appears only in E. faecalis. Thus, using the ABC transporter of the enterocin MR10A/B gene cluster of Enterococcus faecalis MRR10-3 as a cross-resistance model, we aimed to unravel to what extent a particular ABC transporter can be shared across multiple bacteriocinogenic bacterial populations. To this end, we screened the MR10A/B-ABC transporters in available microbial genomes and analyzed their sequence homologies and distribution. Overall, our main findings are as follows: (i) the MR10A/B-ABC transporter is associated with multiple enterocin gene clusters; (ii) the different enterocins associated with this transporter have a saposin-like fold in common; (iii) the Mr10E component of the transporter is more conserved within its associated enterocin, while the Mr10FGH components are more conserved within the carrying species. This is the least known component of the transporter, but it has shown the greatest specificity to its corresponding enterocin. Bacteriocins are now being investigated as an alternative to antibiotics; hence, the wider or narrower distribution of the particular immunity gene should be taken into account for clinical applications to avoid the selection of resistant strains. Further research will be needed to investigate the mechanistic interactions between the Mr10E transporter component and the bacteriocin as well as the specific ecological and evolutionary mechanisms involved in the spread of the immunity transporter across multiple bacteriocins.

show abstract

Advances in Characterizing the Transport Systems of and Resistance to EntDD14, A Leaderless Two-Peptide Bacteriocin with Potent Inhibitory Activity

Cited by 5 publications

References 40 publications

Lack of Polynucleotide Phosphorylase activity in Enterococcus faecalis 14 increases the stability of EntDD14 bacteriocin transcripts

Lack of Polynucleotide Phosphorylase activity in Enterococcus faecalis 14 increases the stability of EntDD14 bacteriocin transcripts

A Review on Enterocin DD14, the Leaderless Two-Peptide Bacteriocin with Multiple Biological Functions and Unusual Transport Pathway

Circular and L50-like leaderless enterocins share a common ABC-transporter immunity gene

Contact Info

Product

Resources

About