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.

Staphylococcus aureus is a major pathogen both within hospitals and in the community. Methicillin, a β-lactam antibiotic, acts by inhibiting penicillin-binding proteins (PBPs) that are involved in the synthesis of peptidoglycan, an essential mesh-like polymer that surrounds the cell. S. aureus can become resistant to methicillin and other β-lactam antibiotics through the expression of a foreign PBP, PBP2a, that is resistant to the action of methicillin but which can perform the functions of the host PBPs. Methicillin-resistant S. aureus isolates are often resistant to other classes of antibiotics (through different mechanisms) making treatment options limited, and this has led to the search for new compounds active against these strains. An understanding of the mechanism of methicillin resistance has led to the discovery of accessory factors that influence the level and nature of methicllin resistance. Accessory factors, such as Fem factors, provide possible new targets, while compounds that modulate methicillin resistance such as epicatechin gallate, derived from green tea, and corilagin, provide possible lead compounds for development of inhibitors.

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(")-Epicatechin gallate (ECg), a component of green tea, sensitizes meticillin-resistant Staphylococcus aureus (MRSA) to b-lactam antibiotics, promotes staphylococcal cell aggregation and increases cell-wall thickness. The potentiation of b-lactam activity against MRSA by ECg was not due to decreased bacterial penicillin-binding protein (PBP) 2a expression or ECg binding to peptidoglycan. A 5-10 % reduction in peptidoglycan cross-linking was observed. Reduced cross-linking was insufficient to compromise the integrity of the cell wall and no evidence of PBP2a activity was detected in the muropeptide composition of ECg-grown cells. ECg increased the quantity of autolysins associated with the cell wall, even though the cells were less susceptible to Triton X-100-induced autolysis than cells grown in the absence of ECg. ECg promoted increased lysostaphin resistance that was not due to alteration of the pentaglycine cross-bridge configuration or inhibition of lysostaphin activity. Rather, decreased lysostaphin susceptibility was associated with structural changes to wall teichoic acid (WTA), an acid-labile component of peptidoglycan. ECg also promoted lipoteichoic acid (LTA) release from the cytoplasmic membrane. It is proposed that ECg reduces b-lactam resistance in MRSA either by binding to PBPs at sites distinct from the penicillin-binding site or by intercalation into the cytoplasmic membrane, displacing LTA from the phospholipid palisade. Thus, ECg-mediated alterations to the physical nature of the bilayer will elicit structural changes to WTA that result in modulation of the cell-surface properties necessary to maintain the b-lactam-resistant phenotype.

Among Escherichia coli organisms isolated at St. Thomas's Hospital during the years 1990 to 1994, the frequency of resistance to amoxicillin-clavulanic acid (tested by disk diffusion in a ratio of 2:1) remained constant at about 5% of patient isolates (10 to 15% of the 41 to 45% that were amoxicillin resistant). Mechanisms of increased resistance were determined for 72 consecutively collected such amoxicillin-clavulanic acid-resistant isolates. MICs of the combination were 16-8 g/ml for 51 (71%) of these and >32-16 g/ml for the remainder. The predominant mechanism was hyperproduction of enzymes isoelectrically cofocusing with TEM-1 (␤-lactamase activities, >200 nmol of nitrocefin hydrolyzed per min per mg of protein) which was found in 44 isolates (61%); two isolates produced smaller amounts (approximately 150 nmol/min/mg) of such enzymes, and two isolates hyperproduced enzymes cofocusing with TEM-2. Eleven isolates produced enzymes cofocusing with OXA-1 ␤-lactamase, which has previously been associated with resistance to amoxicillinclavulanic acid. Ten isolates produced increased amounts of chromosomal ␤-lactamase, and four of these additionally produced TEM-1 or TEM-2. Three isolates produced inhibitor-resistant TEM-group enzymes. In one of the enzymes (pI, 5.4), the amino acid sequence change was Met-673Val, and thus the enzyme is identical to TEM-34. Another (pI, 5.4) had the substitution Met-673Ile and is identical to IRT-I67, which we propose now be given the designation TEM-40. The third (pI, 5.2) had the substitution Arg-2413Thr; this enzyme has not been reported previously and should be called TEM-41. The rarity and diversity of inhibitor-resistant TEM-group enzymes suggest that they are the result of spontaneous mutations that have not yet spread.

L2 writing scholars have recently debated the appropriateness of using cultural constructs to enhance the teaching of English. An important aspect of writing, critical thinking, has received considerable attention. Some have suggested that Asians, including Japanese, do not display critical thought in their writing in English. Other researchers claim that Asians display critical thinking abilities differently than Western learners. In addition, they argue that learners from a particular culture are too diverse to make claims about the whole group's thinking abilities. This study proposes a model for assessing critical thinking in the writing of L2 learners to determine whether content familiarity plays a role in critical thinking. Findings of a study of 45 Japanese undergraduate students indicate that the quality of critical thought depended on the topic content, with a familiar topic generating better critical thinking. Results also suggested that differing assumptions between the L1 and L2 culture may lead to misinterpretations of the critical thinking ability of L2 learners.

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