Enterocin 14 : in vitro, in situ and in vivo activity data
Djamel DIDER & Rozenn RAVALLEC
UMR-T BioEcoAgro INRAe 1158 – Université de Lille, France
Email (djamel.drider@univ-lille.fr) & (rozenn.ravallec@univ-lille.fr)

Enterocin 14 (EntDD14) is a leaderless class IIb bacteriocin produced by Enterococcus faecalis 14, a strain isolated from meconium [1]. Purification and characterization of this bacteriocin revealed that it comprises two complementary peptides EntDD14A (MGAIAKLVAKFGWPIVKKYYKQIMQFIGEGWAINKIIDWIKKHI) and EntDD14B (MGAIAKLVAKFGWPFIKKFYKQIMQFIGQGWTIDQIEKWLKRH) [2]. Bacteriocin’s antimicrobial activity against a panel of Gram-positive and Gram-negative bacteria and microscopic fungi has been studied and the enterocin was active only against a group of genetically related Gram-positive bacteria [1 and new data]. However, this bacteriocin could be of interest for medical purposes due to its activity against potentially dangerous pathogens including Clostridium perfringens and Staphylococcus aureus [1] and its ability to enhance the activity of antibiotics such as erythromycin, kanamycin [3], and methicillin [4]. To verify these results, we conducted in situ studies to establish the EntDD14 efficiency alone or in combination with methicillin in limiting Staphylococcus aureus adhesion to human cells Caco-2. EntDD14 has also been shown to reduce the synthesis of interleukins IL-6 and IL-8 [5]. This activity was validated in vivo using the murine model "holoxenic NMRI-F". We analyzed the impact of the bacteriocin (EntDD14), alone or in combination with erythromycin, against a methicillin-resistant Staphylococcus aureus strain (MRSA) in a murine model infected with this strain. We observed that treatment of the group of mice infected with MRSA (108 cfu) and EntDD14 (165 mg/kg), or EntDD14 (165 mg/kg) combined with erythromycin (100 mg/kg) allowed (i) better histopathological protection of the liver, spleen, and colon, (ii) improved body weight recovery, and (iii) a more stable intestinal microbiota in comparison with untreated infected mice or mice treated only with the antibiotic [6].     

 References.
  1. Al Atya AK, Drider-Hadiouche K, Ravallec R, Silvain A, Vachee A, Drider D (2015). Probiotic potential of Enterococcus faecalis strains isolated from meconium.Frontiers in Microbiology. 2;6:227. doi: 10.3389/fmicb.2015.00227. eCollection 2015.
  2. Caly DL, Chevalier M, Flahaut C, Cudennec B, Al Atya AK, Chataigné G, D'Inca R, Auclair E, Drider D (2017). The safe enterocin DD14 is a leaderless two-peptide bacteriocin with anti-Clostridium perfringens activity.International Journal of Antimicrobial Agents. 49:282-289. doi: 10.1016/j.ijantimicag.2016.11.016. 
  3. Al Atya AK, Belguesmia Y, Chataigne G, Ravallec R, Vachée A, Szunerits S, Boukherroub R, Drider D (2016). Anti-MRSA Activities of Enterocins DD28 and DD93 and Evidences on Their Role in the Inhibition of Biofilm Formation.Frontiers in Microbiology. 31;7:817. doi: 10.3389/fmicb.2016.00817. eCollection 2016.
  4. Belguesmia Y, Spano G, Drider D. (2021). Potentiating effects of leaderless enterocin DD14 in combination with methicillin on clinical methicillin-resistant Staphylococcus aureus S1 strain.Microbiology Research. 252:126864. doi: 10.1016/j.micres.2021.126864.
  5. Teiar R, Pérez-Ramos A, Zgheib H, Cudennec B, Belguesmia Y, Drider D (2022).  Anti-adhesion and Anti-inflammatory Potential of the Leaderless Class IIb Bacteriocin Enterocin DD14.Probiotics and Antimicrobial Proteins. 14(4):613-619. doi: 10.1007/s12602-022-09954-0.
  6.  Bendjeddou K, Hamma-Faradji S, Meddour AA, Belguesmia Y, Cudennec B, Bendali F, Daube G, Taminiau B, Drider D. (2021). Gut microbiota, body weight and histopathological examinations in experimental infection by methicillin-resistant Staphylococcus aureus: antibiotic versus bacteriocin.Beneficial Microbes. 15;12(3):295-305. doi: 10.3920/BM2020.0155.