2-Heptylcyclopropane-1-Carboxylic Acid Disperses and Inhibits Bacterial Biofilms

Abstract

Fatty-acid signaling molecules can inhibit biofilm formation, signal dispersal events, and revert dormant cells within biofilms to a metabolically active state. We synthesized 2-heptylcyclopropane-1-carboxylic acid (2CP), an analog of cis-2-decenoic acid (C2DA), which contains a cyclopropanated bond that may lock the signaling factor in an active state and prevent isomerization to its least active trans-configuration (T2DA). 2CP was compared to C2DA and T2DA for ability to disperse biofilms formed by Staphylococcus aureus and Pseudomonas aeruginosa. 2CP at 125 μg/ml dispersed approximately 100% of S. aureus cells compared to 25% for C2DA; both 2CP and C2DA had significantly less S. aureus biofilm remaining compared to T2DA, which achieved no significant dispersal. 2CP at 125 μg/ml dispersed approximately 60% of P. aeruginosa biofilms, whereas C2DA and T2DA at the same concentration dispersed 40%. When combined with antibiotics tobramycin, tetracycline, or levofloxacin, 2CP decreased the minimum concentration required for biofilm inhibition and eradication, demonstrating synergistic and additive responses for certain combinations. Furthermore, 2CP supported fibroblast viability above 80% for concentrations below 1 mg/ml. This study demonstrates that 2CP shows similar or improved efficacy in biofilm dispersion, inhibition, and eradication compared to C2DA and T2DA and thus may be promising for use in preventing infection for healthcare applications.

Antibacterial Nanoassembled Calix[4]arene Exposing Choline Units Inhibits Biofilm and Motility of Gram Negative Bacteria

“…Compounds reducing preformed biofilm at concentration >100 μg/mL are present in literature. 47,48 Furthermore, it is remarkable that the potency of Chol-Calix may be enhanced by loading an additional antibiofilm agent in the micellar structure, which can entrap active molecules including antibiotics. 25 The disturbance of the bacterial cell membrane could be responsible for the activity on the biofilm as reported for a choline-based ionic liquid.…”

“…For E. coli , a 66.5% reduction was detected at 8 MIC dose corresponding to 150 μg/mL. Compounds reducing preformed biofilm at concentration >100 μg/mL are present in literature. , Furthermore, it is remarkable that the potency of Chol-Calix may be enhanced by loading an additional antibiofilm agent in the micellar structure, which can entrap active molecules including antibiotics …”

Synthesis and Characterization of 2-Decenoic Acid Modified Chitosan for Infection Prevention and Tissue Engineering

“…Synthesized chlorides can modify various chitosan-based biomaterial properties in a nondetrimental way, particularly in that the functionalization imparts hydrophobic properties that limit bacterial attachment and may also allow loading and release of therapeutics [6,7]. The ability to synthesize chlorides that are not commercially available could expand the possible applications to other fatty acid analogs, including cis-2-decenoic acid and 2-heptylcyclopropane-1-carboxylic acid [24,25], to expand possible antimicrobial solutions in the continuing fight against antibiotic resistance and complex biofilm-associated infections.…”

Cis-2-Decenoic Acid and Bupivacaine Delivered from Electrospun Chitosan Membranes Increase Cytokine Production in Dermal and Inflammatory Cell Lines

“…Chitosan flakes (86% DDA) were purchased from Primex (Siglufjordur, Iceland). C2DA was synthesized by the authors as previously described [21]. NHDFs, NHEKs, and their respective media and additives were purchased from Lonza (Basel, Switzerland).…”