Cytinus is small genus of endophytic parasitic plants distributed in South Africa, Madagascar, and in the Mediterranean region. In the latter area, two species occur, Cytinus hypocistis and C. ruber, distinguished by both morphological characters and ecological traits. We characterized the ethanolic and aqueous extracts obtained from the inflorescences of C. hypocistis and C. ruber collected in Sardinia, Italy, and explored their tannin content, antioxidant properties and antimicrobial activities. Total phenolic contents were determined by Folin-Ciocalteu spectrophotometric method. Tannin content was determined by HPLC. Antioxidant activity of the extracts was tested with both electron transfer-based (FRAP, TEAC, DPPH) and spectrophotometric HAT methods (ORAC-PYR). The antimicrobial activities of extracts/compounds were evaluated using the broth microdilution method. The bactericidal activity was evaluated using the time-kill method. Biofilm formation was evaluated by crystal violet (CV) staining assay. Characterization of the tannin profile of C. hypocistis and C. ruber revealed a significant amount of gallotannins, in particular 1-O-galloyl-β-D-glucose. In addition, pentagalloyl-O-β-D-glucose was present in all extracts, reaching the concentration of 0.117 g/kg in the ethanolic extract of C. hypocistis. C. hypocistis extracts displayed a strongest antioxidant activity than C. ruber extracts. Three Gram-positive bacterial species tested (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium) resulted sensitive to both Cytinus extracts, with MICs ranging from 125 to 500 μg/ml for aqueous extracts and from 31.25 to 250 μg/ml for ethanolic extracts; on the contrary, Gram-negative strains (Pseudomonas aeruginosa and Klebsiella pneumoniae) were not affected by Cytinus extracts. Intriguingly, we observed the suppressive activity of ethanolic extracts of C. hypocistis and C. ruber on biofilm formation of S. epidermidis. Experiments performed with synthetic compounds indicated that pentagalloyl-O-β-D-glucose is likely to be one of the active antimicrobial components of Cytinus extracts. These findings show that Cytinus extracts have antimicrobial and antioxidant activities, suggesting a possible application of Cytinus as sources of natural antimicrobials and antioxidants.

It is widely recognized that many chronic infections of the human body have a polymicrobial etiology. These include diabetic foot ulcer infections, lung infections in cystic fibrosis patients, periodontitis, otitis, urinary tract infections and even a proportion of systemic infections. The treatment of mixed infections poses serious challenges in the clinic. First, polymicrobial communities of microorganisms often organize themselves as biofilms that are notoriously recalcitrant to antimicrobial therapy and clearance by the host immune system. Secondly, a plethora of interactions among community members may affect the expression of virulence factors and the susceptibility to antimicrobials of individual species in the community. Therefore, new strategies able to target multiple pathogens in mixed populations need to be urgently developed and evaluated. In this regard, antimicrobial or host defense peptides (AMPs) deserve particular attention as they are endowed with many favorable features that may serve to this end. The aim of the present review is to offer a comprehensive and updated overview of studies addressing the therapeutic potential of AMPs in mixed infections, highlighting the opportunities offered by this class of antimicrobials in the fight against polymicrobial infections, but also the limits that may arise in their use for this type of application.

In the era of antimicrobial resistance, the identification of new antimicrobials is a research priority at the global level. In this regard, the attention towards functional antimicrobial polymers, with biomedical/pharmaceutical grade, and exerting anti-infective properties has recently grown. The aim of this study was to evaluate the antibacterial, antibiofilm, and antiadhesive properties of a number of quaternized chitosan derivatives that have displayed significant muco-adhesive properties and wound healing promotion features in previous studies. Low (QAL) and high (QAH) molecular weight quaternized chitosan derivatives were synthetized and further modified with thiol moieties or pendant cyclodextrin, and their antibacterial activity evaluated as minimal inhibitory concentrations (MIC) and minimal bactericidal concentrations (MBC). The ability of the derivatives to prevent biofilm formation was assessed by crystal violet staining. Both QAL and QAH derivatives exerted a bactericidal and/or inhibitory activity on the growth of P. aeruginosa and S. epidermidis. The same compounds also showed marked dose-dependent anti-biofilm activity. Furthermore, the high molecular weight derivative (QAH) was used to functionalize titanium plates. The successful functionalization, demonstrated by electron microscopy, was able to partially inhibit the adhesion of S. epidermidis at 6 h of incubation. The shown ability of the chitosan derivatives tested to both inhibit bacterial growth and/or biofilm formation of clinically relevant bacterial species reveals their potential as multifunctional molecules against bacterial infections.

The increasing frequency of multi-drug resistant microorganisms has driven research into alternative therapeutic strategies. In this respect, natural antimicrobial peptides (AMPs) hold much promise as candidates for the development of novel antibiotics. However, AMPs have some intrinsic drawbacks, such as partial degradation by host proteases or inhibition by host body fluid composition, potential toxicity, and high production costs. This review focuses on the hepcidins, which are peptides produced by the human liver with a known role in iron homeostasis, as well by numerous other organisms (including fish, reptiles, other mammals), and their potential as antibacterial and antifungal agents. Interestingly, the antimicrobial properties of human hepcidins are enhanced at acidic pH, rendering these peptides appealing for the design of new drugs targeting infections that occur in body areas with acidic physiological pH. This review not only considers current research on the direct killing activity of these peptides, but evaluates the potential application of these molecules as coating agents preventing biofilm formation and critically assesses technical obstacles preventing their therapeutic application.

Pseudomonas aeruginosa is a major cause of chronic lung infections in cystic fibrosis (CF) patients. The ability of the bacterium to form biofilms and the presence of a thick and stagnant mucus in the airways of CF patients largely contribute to antibiotic therapy failure and demand for new antimicrobial agents able to act in the CF environment. The present study investigated the anti-P. aeruginosa activity of lin-SB056-1, a recently described semi-synthetic antimicrobial peptide, used alone and in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA). Bactericidal assays were carried out in standard culture conditions and in an artificial sputum medium (ASM) closely resembling the CF environment. Peptide’s structure and interaction with large unilamellar vesicles in media with different ionic strengths were also investigated through infrared spectroscopy. Lin-SB056-1 demonstrated fast and strong bactericidal activity against both mucoid and non-mucoid strains of P. aeruginosa in planktonic form and, in combination with EDTA, caused significant reduction of the biomass of P. aeruginosa mature biofilms. In ASM, the peptide/EDTA combination exerted a strong bactericidal effect and inhibited the formation of biofilm-like structures of P. aeruginosa. Overall, the results obtained highlight the potential of the lin-SB056-1/EDTA combination for the treatment of P. aeruginosa lung infections in CF patients.