Antibacterial activity of N(alpha)-benzoylarginine-based surfactants and their possible mechanism of action

FAIT, MARÍA ELISA; VAZQUEZ ROMINA; VELA, M. ELENA; BAKÁS LAURA; DI SANTO-MEZTLER P.; MATÉ SABINA; LORENZO, J.; HERMET, MELISA; PRAT A.; DAZA MILLONE, M. ANTONIETA; MORCELLE, SUSANA

Southampton (conferencia virtual)

Simposio; 6th Young Microbiologists Symposium on Microbe Signalling, Organisation and Pathogenesis (Virtual Conference); 2020

The Federation of European Microbiological Societies (FEMS)

Amino acid-based surfactants consist in a class of compounds of amphiphilic characteristics which have a chemical structure similar to natural lipoaminoacids. They have shown very interesting properties, being the antimicrobial activity one of the most relevant. Within this context, arginine-based tensioactives are considered as the most promising of the family, since they have a satisfactory toxicity profile, high biodegradability, low impact strategy of manufacture and a wide biocidal spectrum. In the present communication we describe the antimicrobial activity of four monocatenary cationic arginine-based surfactants that our group obtained by an enzymatic strategy synthesis. Bz-Arg-NHC10∙HX (being X: Cl or Br, see Fig. 1) were synthetized using papain as biocatalyst and purified through an eco-friendly methodology.The biocidal activity of the four compounds was assayed against a panel consisting on gram positive and gram negative bacterial strains. Interestingly, all the surfactants obtained demonstrated to be effective against the microorganisms tested.It is well known that cationic amino acid-base surfactants interact with the lipid bilayer of microorganisms, resulting in cell death through membrane disruption. This fact has been demonstrated for arginine-based surfactants having dfferent structures [1]. However, some of these tensioactives have shown poor or not activity against gram negative bacteria [2, 3]. As can be seen in Table 1, our compounds showed an interesting antimicrobial action against the gram negative strains tested. In order to gain an insight into the understanding of the biocidal effect of our tensioactives, the ability of Bz-Arg-NHC10∙HCl to interact with the phospholipid layer of the bacterial cell by using as a model membrane composed by 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was studied. Bz-Arg-NHC10∙HCl was able to insert into DPPC monolayers. It also fluidized DPPC bilayers, as demonstrated through differential thermal analysis (DSC). Furthermore, atomic force microscopy (AFM) and surface plasmon resonance (SPR), revealed that Bz-Arg-NHC10∙HCl disrupted the DPPC bilayer, causing the release of lipid-surfactant mixed micelles at saturation of the compound. Although further investigations involving the interaction of Bz-Arg-NHC10∙HCl with model membranes of different composition, the results obtained would indicate that the benzoyl group attached to the polar head of the compound would be the responsible of the increased antimicrobial activity against Gram negative bacteria when compared with other arginine-based surfactants.References[1] Castillo JA, Pinazo A, Carilla J, Infante MR, Alsina MA, Haro I, Clapés P (2004) Interaction of Antimicrobial Arginine-Based Cationic Surfactants with Liposomes and Lipid Monolayers. Langmuir 20:3379?3387. doi: 10.1021/la036452h.[2] Morán C, Clapés P, Comelles F et al (2001b) Chemical structure/property relationship in single-chain arginine surfactants. Langmuir 17:5071?5075. doi:10.1021/la010375d.[3] Pérez L, García MT, Ribosa I et al (2002) Biological properties of arginine-based gemini cationic surfactants. Environ Toxicol Chem 21:1279?1285.