Ceragenin CSA-44 as a Means to Control the Formation of the Biofilm on the Surface of Tooth and Composite Fillings

Abstract

Recurrent oral infections, as manifested by endodontic and periodontal disease, are often caused by Enterococcus faecalis (E. faecalis) and Candida albicans (C. albicans). Here, we assessed the anti-biofilm activity of ceragenin CSA-44 against these microbes growing as a biofilm in the presence of saliva on the surface of human teeth and dental composite (composite filling) subjected to mechanical stresses. Methods: Biofilm mass analysis was performed using crystal violet (CV) staining. The morphology, viscoelastic properties of the biofilm after CSA-44 treatment, and changes in the surface of the composite in response to biofilm presence were determined by AFM microscopy. Results: CSA-44 prevented biofilm formation and reduced the mass of biofilm formed by tested microorganisms on teeth and dental composite. Conclusion: The ability of CSA-44 to prevent the formation and to reduce the presence of established biofilm on tooth and composite filling suggests that it can serve as an agent in the development of new methods of combating oral pathogens and reduce the severity of oral infections.

Efficacy of Ceragenins in Controlling the Growth of Oral Microorganisms: Implications for Oral Hygiene Management

“…Our earlier study demonstrated that while antibacterial activities of LL-37 and its synthetic analog-WLBU2 are inhibited by salivary mucin, CSA-13 activity against P. aeruginosa PA01 and E. coli MG1655 are undisturbed [ 41 ]. Biofilm formation of C. albicans and E. faecalis on teeth and dental composite was also significantly inhibited despite the presence of saliva [ 45 ]. Accordingly, the presence of saliva did not affect the bactericidal and fungicidal effects of ceragenins [ 41 , 46 ] and was only marginally affected by the addition of dental plaque suspension [ 46 ].…”

Antimicrobial Growth Promoters Altered the Function but Not the Structure of Enteric Bacterial Communities in Broiler Chicks ± Microbiota Transplantation

“…We investigated the use of the ceragenin, CSA-44 [ 21 ] as a novel AGP, along with oral transplantation of cecal microbiota as a method of improving bird growth and increasing enteric bacterial community diversity in young broiler chickens. Additionally, the individual effects of virginiamycin, CSA-44, and microbiota transplantation on the intestinal community establishment, structure, and function were examined.…”

“…CSA-44, the molecule used in the current study is bactericidal to a variety of bacteria, including Escherichia coli , Enterobacter cloacae , and Klebsiella pneumonia [ 65 ]. Additionally, a recent study by Tokajuk et al [ 21 ] observed that CSA-44 was able to prevent and reduce biofilm formation by oral bacterial and fungal pathogens, including Enterococcus faecalis and Candida albicans . This suggests that ceragenins may have value as AGPs.…”

“…On day 3, randomly selected chicks were assigned to one of the three following diet treatments: (1) unamended starter ration (control treatment) [ 2 ]; (2) starter ration containing 20 mg/kg virginiamycin (Phibro, Teaneck, NJ, USA); and (3) starter ration containing 620 mg/kg of synthesized CSA-44 (CSA treatment) [ 21 ] ( Table S1 ). Diet treatments were custom formulated at the AAFC LeRDC Feed Mill.…”

“…In this regard, we investigated the effects of the conventional AGP, virginiamycin, and an alternative AGP candidate (i.e., the ceragenin, CSA-44) on the structure and function of the cecal microbiota. As the use of AMPs, including AMP mimics, is an active area of research in human medicine, we chose to examine the impact of the cathelicidin mimic, CSA-44 [ 21 ], as a potential growth promoter in chickens. We have previously shown that the early establishment of a diverse microbiota in chicks has profound impacts on the health of the birds [ 2 ], and microbiota transplantation was included as an experimental variable to address the impact of the early establishment of a diverse and homogeneous microbiota on the AGP-host-microbiota interaction.…”