Disruption of d-alanyl esterification of Staphylococcus aureus cell wall teichoic acid by the β-lactam resistance modifier (−)-epicatechin gallate

Abstract

ObjectivesThe naturally occurring polyphenol (−)-epicatechin gallate (ECg) increases oxacillin susceptibility in mecA-containing strains of Staphylococcus aureus. Decreased susceptibility to lysostaphin suggests alterations to the wall teichoic acid (WTA) content of ECg-grown bacteria. Changes in WTA structure in response to ECg were determined.MethodsNuclear magnetic resonance spectroscopy of purified monomers from S. aureus was used to elucidate WTA structures. Molecular modelling of WTA chains was employed to determine their spatial configuration.ResultsECg-grown methicillin-resistant S. aureus (MRSA) strains BB568 and EMRSA-16 displayed markedly reduced resistance to oxacillin, had thickened cell walls and separated poorly. Growth in ECg-supplemented medium reduced the substitution of the WTA backbone by d-alanine (d-Ala); ratios of N-acetyl glucosamine to d-Ala were reduced from 0.6 and 0.49 (for BB568 and EMRSA-16) to 0.3 and 0.28, respectively. Molecular simulations indicated a decrease in the positive charge of the bacterial wall, confirmed by increased binding of cationized ferritin, and an increase in WTA chain flexibility to a random coil conformation.ConclusionsStructural elucidation and molecular modelling of WTA indicated that conformational changes associated with reduced d-Ala substitution may contribute to the increased susceptibility of MRSA to β-lactam antibiotics and account for other elements of the ECg-induced phenotype.

Bacteriophage-derived enzyme that depolymerizes the alginic acid capsule associated with cystic fibrosis isolates ofPseudomonas aeruginosa

“…Non-O-acetylated sodium alginate extracted from brown algae was purchased from Sigma-Aldrich (Poole, UK). To monitor the quality of purified material, relevant structural features of alginates were determined using 3 H NMR as described previously (Bernal et al 2009). …”

Interaction with Polyphenols and Antibiotics

“…The most of them are able to suppress a number of microbial virulence factors (such as inhibition of biofilm formation, reduction of host ligands adhesion and neutralization of bacterial toxins) and show synergistic effect with antibiotics [38]. Several studies on the antibacterial activity of flavonoid-rich products was reported that new compounds of flavonoid with bactericidal rather than bacteriostatic effect was increasing the activity of antibiotics through synergistic interactions [5,16,21]. Staphylococcus aureus and methicillin resistant S. aureus (MRSA) are among the most significant gram-positive pathogens.…”

Mechanism of the combined anti-bacterial effect of green tea extract and NaCl against Staphylococcus aureus and Escherichia coli O157:H7

“…However, nearly all measurements of anti-bacterial activity have been performed using agar media, and given the practical application in actual foodstuffs, the anti-bacterial activity of catechin in liquid media needs to be clarified. In addition, studies examining the mode of action of catechins have indicated that hydrogen peroxide generated by catechins (Akagawa, Shigemitsu, Suyama, 2003;Arakawa, 2004;Nakayama, Ichiba, Kuwabara, Kajiya, Kumazawa, 2002) acts to destroy bacteria and that catechins attach and cause damage to the lipid bilayer membrane of bacteria (Bernal, Zloh, Taylor, 2009;Caturla, Vera-Samper, Villalaín, Mateo, Micol, 2003;Nakayama, Shigemune, Tsugukuni, Tokuda, & Miyamoto, 2011;Tsuchiya, 2001). However, many of the details related to the bactericidal action of catechins remain unclear.…”