Anti-Staphylococcus aureus activity and oxacillin resistance modulating capacity of 3-O-acyl-catechins.

Epicatechin gallate (ECg), a component of green tea with weak activity against Staphylococcus aureus, reduces oxacillin resistance in methicillin-resistant S. aureus at concentrations below the MIC. Because catechins bind to artificial lipid bilayers, we investigated whether the anti-staphylococcal activity of catechins could be improved by increasing their capacity to interact with the cytoplasmic membrane. Substitution of the gallate group of ECg with 3-O-acyl chains of varying lengths (C(4)-C(18)) led to enhanced anti-staphylococcal activity with chain lengths of C(8) (octanoyl) and C(10) (decanoyl). 3-O-octanoyl catechin was bactericidal against MRSA as the result of membrane damage. 3-O-acyl catechins tested at a 1/4 MIC did not reduce the oxacillin MIC greater than two-fold. 3-O-acyl catechins warrant further investigation as anti-staphylococcal agents.

Modulation of beta-lactam resistance in Staphylococcus aureus by catechins and gallates.

Aqueous extracts of Japanese green tea (Camellia sinensis) are able to reverse beta-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA). We have attributed the capacity to reverse oxacillin resistance in the homogeneous PBP2a producer BB568 and in EMRSA-16 to (-)-epicatechin gallate (ECG) and (-)-catechin gallate (CG). Minimum inhibitory concentration (MIC) values for oxacillin were reduced from 256 and 512 to 1-4 mg/l, respectively, in the presence of these polyphenols. In addition, (-)-epigallocatechin gallate (EGCG) had a moderate capacity to modulate oxacillin activity against S. aureus BB568, but none against EMRSA-16. ECG, CG and EGCG increased the sensitivity of EMRSA-15 to oxacillin. The gallate moiety was essential for the oxacillin-modulating activity of ECG, as both (-)-epicatechin and (-)-epicatechin-3-cyclohexylcarboxylate were unable to reverse resistance to oxacillin. Gallic acid and three alkyl gallates (methyl gallate, propyl gallate, and octyl gallate) did not modulate beta-lactam resistance in MRSA. Octyl gallate exhibited direct antibacterial activity against S. aureus BB568 (16 mg/l). Modulation of beta-lactam resistance by ECG significantly enhanced the activities of flucloxacillin and the carbapenem antibiotics imipenem and meropenem against 40 MRSA isolates, with MIC(90) values for the antibiotics reduced to the susceptibility breakpoint or below. Consequently, EGCG, CG and, particularly, ECG warrant further investigation as agents to combat beta-lactam resistance in S. aureus.

Chemical and microbiologic aspects of penems, a distinct class of beta-lactams: focus on faropenem.

Many beta-lactam antimicrobials were developed between the 1960s and 1980s, with continuing development driven by the emergence of microbial resistance. Penems form a discrete class of beta-lactams that comprises structural hybrids of penicillins (penams) and cephalosporins (cephems). The chemistry and microbiology of the representative penems MEN 10700, ritipenem, CGP 31608, sulopenem, BRL 42715, and faropenem are reviewed. Particular emphasis is placed on faropenem, which is in late clinical development.

Antimicrobial properties of green tea catechins.

Extracts of leaves from the tea plant Camellia sinensis contain polyphenolic components with activity against a wide spectrum of microbes. Studies conducted over the last 20 years have shown that the green tea polyphenolic catechins, in particular (-)-epigallocatechin gallate (EGCg) and (-)-epicatechin gallate (ECg), can inhibit the growth of a wide range of Gram-positive and Gram-negative bacterial species with moderate potency. Evidence is emerging that these molecules may be useful in the control of common oral infections, such as dental caries and periodontal disease. Sub-inhibitory concentrations of EGCg and ECg can suppress the expression of bacterial virulence factors and can reverse the resistance of the opportunistic pathogen Staphylococcus aureus to beta-lactam antibiotics. For example, relatively low concentrations of ECg can sensitize methicillin-resistant S. aureus (MRSA) clinical isolates to levels of oxacillin that can be readily achieved in clinical practice. Catechin gallates such as ECg intercalate into phopsholipid bilayers and it is likely that they affect both virulence and antibiotic resistance by perturbing the function of key processes associated with the bacterial cytoplasmic membrane.