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.
Highlights
A biofilm is an aggregate of microbial cells that attaches to various surfaces, including tissue and medical implants (Stoodley et al, 2013; Saeed et al, 2019)
We evaluated the hypothesis that 2heptylcyclopropane-1-carboxylic acid (2CP) disperses and inhibits biofilm using in vitro assays of S. aureus and P. aeruginosa biofilm dispersion
We further evaluated the combination of 2CP with antibiotics to identify synergistic and additive responses through minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC) assays compared to cis-2-decenoic acid (C2DA) and T2DA
Summary
A biofilm is an aggregate of microbial cells that attaches to various surfaces, including tissue and medical implants (Stoodley et al, 2013; Saeed et al, 2019). Almost 80% of human infections are caused by the development of biofilms by pathogenic bacterial strains such as Staphylococcus aureus, Staphylococcus epidermis, Pseudomonas aeruginosa, and Escherichia coli (Brady et al, 2006) The attachment of these and other bacterial strains to implant or tissue surfaces to form biofilms poses a particular risk for recurring infections, as the cells within a biofilm are resistant to both antibiotics and immune cell clearance (Bauer and Grosso, 2013). Immobilized subgroups of bacterial cells within the biofilm have decreased metabolic activity and can increase the minimum inhibitory concentration of antibiotics up to 1,000 times higher for biofilms compared to planktonic bacteria (Keren et al, 2004) These and other complexities associated with biofilm infections have led to extensive research of their mechanism of action and potential novel treatments
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