P-coumaric acid inhibits biofilm formation in pellicles and association with meropenem shows synergistic effect against Acinetobacter baumannii

Samily Aquino Sá Oliveira , Danillo Sales Rosa , Renata de Faria Silva Souza , Amaro Antônio Silva Neto , Edilson do Carmo Marins Júnior , Márcio Rennan Santos Tavares , Maísa Mota Antunes , Gustavo Batista de Menezes , Vasco Ariston de Carvalho Azevero , Flavia Figueira Aburjaile , Jackson Roberto Guedes da Silva Almeida , Daniel Rodrigo Cavalcante de Araújo , Fabiane Rabelo da Costa Batista , Carine Rosa Naue , Mateus Matiuzzi da Costa
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Abstract

Acinetobacter baumannii is one of the main causes of hospital infections and has shown broad resistance to antimicrobials. Therefore, effective alternatives are needed to combat this species. From this perspective, this study aimed to search for an antimicrobial alternative using products of natural origin with the potential to combat multidrug-resistant A. baumannii (MDR). Initially, the crude ethanolic extract (CEE) from Hymenaea martiana leaves was prepared, which went through phytochemical screening and compound analysis by high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD). The minimum inhibitory concentration and the minimum bactericidal concentration of CEE, as well as secondary metabolites detected in HPLC, were determined using nine isolates of A. baumannii MDR. The motility and formation of biofilms on solid-liquid interfaces and in pellicles were verified, as well as the interference of secondary metabolites on these virulence factors. The synergistic combination of secondary metabolites and meropenem was also evaluated. In the HPLC-DAD analysis, gallic acid (GA), p-coumaric acid (PA), and rutin were detected. Antimicrobial activity was found for CEE, GA, and PA. PA showed antibiofilm potential, especially on the pellicle. Both phenolic acids showed excellent synergistic activity, reversing resistance to meropenem in some cases. The PA-meropenem combination showed good results, and its use rescues the sensitivity of an already known antibiotic, combined with a substance with antibiofilm activity. These results provide a path for the use of new antimicrobial therapies that may assist in treating A. baumannii.
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