Abstract
Antimicrobial resistance poses a serious threat to human health worldwide. Plant compounds may help to overcome antibiotic resistance due to their potential resistance modifying capacity. Several botanical extracts and pure polyphenolic compounds were screened against a panel of eleven bacterial isolates with clinical relevance. The two best performing agents, Cistus salviifolius (CS) and Punica granatum (GP) extracts, were tested against 100 Staphylococcus aureus clinical isolates, which resulted in average MIC50 values ranging between 50–80 µg/mL. CS extract, containing hydrolyzable tannins and flavonoids such as myricetin and quercetin derivatives, demonstrated higher activity against methicillin-resistant S. aureus isolates. GP extract, which contained mostly hydrolyzable tannins, such as punicalin and punicalagin, was more effective against methicillin-sensitive S. aureus isolates. Generalized linear model regression and multiple correspondence statistical analysis revealed a correlation between a higher susceptibility to CS extract with bacterial resistance to beta-lactam antibiotics and quinolones. On the contrary, susceptibility to GP extract was related with bacteria sensitive to quinolones and oxacillin. Bacterial susceptibility to GP and CS extracts was linked to a resistance profile based on cell wall disruption mechanism. In conclusion, a differential antibacterial activity against S. aureus isolates was observed depending on antibiotic resistance profile of isolates and extract polyphenolic composition, which may lead to development of combinatorial therapies including antibiotics and botanical extracts.
Highlights
Antimicrobial resistance poses a serious threat to human health worldwide
By using different statistical approaches, we investigated if the polyphenolic composition or the type of extract might play a role in the bacterial susceptibility, according to the antibiotic resistance profile and mechanism involved in the resistance
A panel consisting of 3 different plant extracts (CS, C. salviifolius; PN, Citrus paradisi; GP, P. granatum) and 7 pure polyphenolic compounds (GA, gallic acid; P, punicalagin; Q3G, quercetin-3-glucuronide; M, myricetin; N, naringenin; EA, ellagic acid) was initially selected for the first antimicrobial screening based on existing literature and previous experiments of the research group in which these agents showed activity against bacterial models[9,12]
Summary
Antimicrobial resistance poses a serious threat to human health worldwide. Plant compounds may help to overcome antibiotic resistance due to their potential resistance modifying capacity. Pharmaceutical companies are uncertain when investing in the development of new antibiotics due to the possibility of rapid bacterial resistance development, resulting in an inability to recover their investment[2]. As traditional drug therapies are losing efficacy, novel therapies based on natural antimicrobial compounds are emerging as alternative or complementary treatments against nosocomial infections Natural combinations such as plant extracts containing a wide range of different molecules, including polyphenols, have demonstrated antimicrobial activity. These combinations can act against many different bacterial molecular targets, sometimes. Universidad s/n, 03202 Elche, Spain. 4CIBER, Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Instituto de Salud Carlos III (CB12/03/30038), Madrid, Spain. 5These authors jointly supervised this work: Enrique
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