Phloretin derived from apple can reduce alpha-hemolysin expression in methicillin-resistant Staphylococcus aureus USA300

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has become increasingly important because it is the most common cause of hospital-acquired infections, which have become globally epidemic. Our study specifically focused on the MRSA strain USA300, which was shown in 2014 to be responsible for the most current pandemic of highly virulent MRSA in the United States. We aimed to evaluate the in vitro effect of phloretin on USA300. Susceptibility testing, western blotting assays, hemolysis assays and real-time RT-PCR were employed to examine the in vitro effects of phloretin on alpha-hemolysin (Hla) production when the bacterium was co-cultured with phloretin. The protective effect of phloretin against the USA300-mediated injury of human alveolar epithelial cells (A549) was tested using the live/dead analysis and cytotoxicity assays. We showed that sub-inhibitory concentrations of phloretin have no effect on bacterial viability; however, they can markedly inhibit the production of Hla in culture supernatants and the transcriptional levels of hla (the gene encoding Hla) and agrA (the accessory gene regulator). Phloretin, at a final concentration of 16 µg/ml, could protect A549 cells from injury caused by USA300 in the co-culture system. Our study suggests that phloretin might have a potential application in the development of treatment for MRSA infections.

Chalcone Attenuates Staphylococcus aureus Virulence by Targeting Sortase A and Alpha-Hemolysin

“…For this reason, therapeutic agents targeting virulence factors, such as SrtA and Hla, which do not threaten survival, may not lead to the development of resistance as quickly as conventional antibiotics typically do, and this will have important implications for S. aureus infection. Some agents targeting S. aureus SrtA or Hla have been found previously (Liu et al, 2015 ; Zhou et al, 2015 ; Zhang et al, 2016 ). However, as these compounds are targeted only at one kind of virulence factor, the limitations for clinical treatment will certainly exist.…”

Phloretin, an Apple Phytoalexin, Affects the Virulence and Fitness of Pectobacterium brasiliense by Interfering With Quorum-Sensing

“…Moreover, many of the virulence associated phenotypes were also inhibited at 0.2 mM phloretin, a concentration that did not compromise bacterial growth. Phloretin has been reported to reduce motility and biofilm formation in several Gram-positive and Gram-negative bacteria (Zhou et al, 2015;Wang et al, 2017;Adil et al, 2019). Biofilms are complex three-dimensional structures of bacteria in a matrix consisting of exopolysaccharides (EPS), protein, lipids and extracellular DNA, attached to a biotic or abiotic solid surface (Castiblanco and Sundin, 2016).…”

Identification of Ellagic Acid Rhamnoside as a Bioactive Component of a Complex Botanical Extract with Anti-biofilm Activity

“…As phenol and catechol are key structural components of EA ( Figures 1 , 2 ) and other phenolic compounds have shown anti-biofilm and anti-quorum sensing activity (Cowan, 1999; Brielmann, 2010; Gutierrez-Barranquero et al, 2015; Onsare and Arora, 2015; Zhou et al, 2015; Tsou et al, 2016), they were chosen as targets to determine the structural elements of the EA core required for bioactivity. Phenol and catechol containing compounds are widely observed in plant natural products (Cowan, 1999; Brielmann, 2010), suggesting that they may occur within R. ulmifolius .…”