Synergistic Antimicrobial Action of Lactoferrin-Derived Peptides and Quorum Quenching Enzymes

Abstract

Combined use of various antimicrobial peptides (AMPs) with enzymes that hydrolyze the signaling molecules of the resistance mechanism of various microorganisms, quorum sensing (QS), to obtain effective antimicrobials is one of the leading approaches in solving the antimicrobial resistance problem. Our study investigates the lactoferrin-derived AMPs, lactoferricin (Lfcin), lactoferampin and Lf(1-11), as potential partners for combination with enzymes hydrolyzing lactone-containing QS molecules, the hexahistidine-containing organophosphorus hydrolase (His6-OPH) and penicillin acylase, to obtain effective antimicrobial agents with a scope of practical application. The possibility of the effective combination of selected AMPs and enzymes was first investigated in silico using molecular docking method. Based on the computationally obtained results, His6-OPH/Lfcin combination was selected as the most suitable for further research. The study of physical–chemical characteristics of His6-OPH/Lfcin combination revealed the stabilization of enzymatic activity. A notable increase in the catalytic efficiency of action of His6-OPH in combination with Lfcin in the hydrolysis of paraoxon, N-(3-oxo-dodecanoyl)-homoserine lactone and zearalenone used as substrates was established. Antimicrobial efficiency of His6-OPH/Lfcin combination was determined against various microorganisms (bacteria and yeasts) and its improvement was observed as compared to AMP without enzyme. Thus, our findings demonstrate that His6-OPH/Lfcin combination is a promising antimicrobial agent for practical application.

Metal Nanomaterials and Hydrolytic Enzyme-Based Formulations for Improved Antifungal Activity

“…The ability of individual enzymes to catalyze the hydrolysis of fungal QSMs allows them to be attributed to the so-called Quorum Quenching enzymes (QQE). Gluconolactonase- [138]) and hexahistidine-containing organophosphorus hydrolase (His 6 -OPH) [139,140] esterases [141,142]) have been identified as such enzymes acting against fungi today (Table 5).…”

“…A. niger Lactone-containing QSMs His 6 -OPH [139,140] Trichosporon beigelii, Candida sp., S. cerevisiae, Pachysolen tannophilus, Kluyveromyces marxianus Lactone-containing QSMs Esterases [141,142] Mucor mucedo, Blakeslea trispor Phycomyces blakesleeanus…”

Recent Advances on Antimicrobial Peptides from Milk: Molecular Properties, Mechanisms, and Applications

“…Consequently, bLFH (bovine lactoferrin) has been adopted as a supplementary for multiple foods, particularly newborn dairy products, to improve infants' innate defenses and protect against detrimental microbial contamination. 133 Furthermore, Aslanli et al 134 generated a combination of QQ enzyme His 6 -OPH with milk protein derived AMP Lfcin, which is capable of being adopted as a bioactive additive for various newborn dairy-based products. A recent study developed a double-coating system using alginate microparticles loaded with Ctx (Ile 21 )-Ha AMP that showed potent activity against pathogenic bacteria causing infectious diseases, such as Salmonella spp.…”

Various Biomimetics as Antifungals

“…Combination of metalloenzyme such as hexahistidine-containing organophosphorus hydrolase (His6-OPH), capable of hydrolyzing signal molecules of yeast QS, with AFPs (polymyxins, bacitracin, Lfcin) resulted in a notable improvement of antimicrobial efficiency of action of the AFPs (up to 8.5 times) against different yeast species, such as Saccharomyces cerevisiae, Candida sp., Trichosporon beigeii, etc. It is interesting, that His6-OPH had an increased catalytic efficiency of action in the hydrolysis of its substrates (QS molecules) when it was introduced in combination with AFPs [143,144]. Thus, combination of the AFPs with enzymes possessing antifungal activity is a perspective trend in the development of efficient antifungals.…”