A new water-soluble bactericidal agent for the treatment of polymicrobial infections

Abstract

Grapefruit and lemon pectin obtained from the respective waste citrus peels via hydrodynamic cavitation in water only are powerful, broad-scope antimicrobial alternatives to antibiotics against Gram-negative and -positive pathogens. Dubbed IntegroPectin, these pectic polymers functionalized with citrus flavonoids and terpenes show superior antimicrobial activity when compared to commercial citrus pectin. Similarly to commercial pectin, lemon IntegroPectin determined ca. 3 log reduction of Staphylococcus aureus cells, while an enhanced activity of commercial citrus pectin was detected in the case of Pseudomonas aeruginosa cells with a minimal bactericidal concentration (MBC) of 15 mg mL-1. Although grapefruit and lemon IntegroPectin share equal MBC in the case of P. aeruginosa cells, grapefruit IntegroPectin shows boosted activity upon exposure of S. aureus cells with a 40 mg mL-1 biopolymer concentration being sufficient to achieve complete killing of the bacterial cells. Insight on the mechanism of action of these biocompatible antimicrobials and their effect on bacterial cells, at the morphological level, were obtained indirectly through Fourier Transform Infrared spectroscopy and directly through scanning electron microscopy. In the era of antimicrobial resistance, these results are of great societal and sanitary relevance as they open new avenues to develop innovative antimicrobials for the treatment of polymicrobial infections unlikely to develop drug resistance.

CytroCell micronized cellulose enhances the structural and thermal properties of IntegroPectin cross-linked films

“…Figure 4 shows that all the typical FTIR absorption bands of pectin and cellulose are observed for each film, with the broad signal of O-H stretching mode at 3275 cm −1 broad signal In agreement with the FTIR spectrum of grapefruit IntegroPectin, 24 also the composite grapefruit IntegroPectin/CytroCell films showed one large ns(C=O) stretching mode signal centered at ~1716 cm −1 of carboxylate groups and another at ~1600 cm −1 due to νas(COO -). 28 Added to water, the films do not dissolve and only moderately swell after several days of immersion in water (Figure 5), eventually leaching in solution most water-soluble adsorbed molecules.…”

“…In the case of grapefruit IntegroPectin/CytroCell films, cellulose depolymerization takes place at ~400-405 °C. We ascribe the ability of the IntegroPectin polymeric chains to protect and stabilize the incorporated cellulose fibrils to the strong hydrogen bonds forming between the free carboxylic acid groups of low esterified grapefruit IntegroPectin (degree of esterification of 14%) 24 and the grapefruit CytroCell cellulose fibrils consisting of highly ramified microfibrils with diameter ranging from 500 nm to 1000 nm. 19 The DSC thermograms of all films show a broad endothermic curve within the whole temperature range studied.…”

Red Orange and Bitter Orange IntegroPectin: Structure and Main Functional Compounds

“…This, once again, is due to the adsorption and concentration process taking place during the HC-based extraction process followed by freezedrying of the aqueous extract rich in flavonoids released into the aqueous phase most likely with pectin acting as emulsifying agent. For comparison, the overall amount of polyphenols found in grapegruit IntegroPectin, a powerful and broad-scope antibacterial agent, 6 was about 75 mg/g. 29 The high amount of naringin (47.16 mg/g), about half of that found in grapefruit IntegroPectin (73.66 mg/g), imparts the bitter taste to C. aurantium due to the sugar neohesperidose, in contrast to rutinose of hesperidin that causes these flavanones to have a neutral taste.…”

“…4 The process has been subsequently extended to other citrus processing biowastes, including those of lemon 5 and grapefruit. 6 Invariably, the citrus pectin thereby obtained contained large amounts of citrus flavonoids and terpenes, with a uniquely low DE of these pectins readily isolated after the HC-based extraction via freeze-drying. Accordingly, we dubbed "IntegroPectin" these whole citrus pectins to differentiate them from conventional citrus pectin industrially extracted via conventional acid hydrolysis of citrus or apple juice processing waste.…”

Pectin: New Science and Forthcoming Applications of the Most Valued Hydrocolloid

“…[15] Recently, for example the broad-scope antibacterial activity of a new citrus pectin ("IntegroPectin") obtained from lemon and grapefruit processing waste via hydrodynamic cavitation has been demonstrated in vitro, suggesting the origins of said enhanced antimicrobial activity. [16] "Tremendous progress in our understanding of the very complex fine structure of pectic polymers" wrote in 2006 researchers at a large pectin manufacturer, allow producers "to develop a new generation of sophisticated designer pectins with specific functionalities". [17] In this study, we offer a unified perspective on the new science and technology of pectin.…”