The crystal structure of a family GH25 lysozyme from Bacillus anthracis implies a neighboring-group catalytic mechanism with retention of anomeric configuration.

Lysozymes are found in many of the sequence-based families of glycoside hydrolases (www.cazy.org) where they show considerable structural and mechanistic diversity. Lysozymes from glycoside hydrolase family GH25 adopt a (alpha/beta)(5)(beta)(3)-barrel-like fold with a proposal in the literature that these enzymes act with inversion of anomeric configuration; the lack of a suitable substrate, however, means that no group has successfully demonstrated the configuration of the product. Here we report the 3-D structure of the GH25 enzyme from Bacillus anthracis at 1.4A resolution. We show that the active center is extremely similar to those from glycoside hydrolase families GH18, GH20, GH56, GH84, and GH85 implying that, in the absence of evidence to the contrary, GH25 enzymes also act with net retention of anomeric configuration using the neighboring-group catalytic mechanism that is common to this 'super-family' of enzymes.

Inappropriate treatment of catheter-associated asymptomatic bacteriuria in a tertiary care hospital.

BACKGROUND: Evidence-based guidelines state that asymptomatic bacteriuria is not a clinically significant condition in men and nonpregnant women and that treatment is unlikely to confer clinical benefit. We hypothesized that, among patients with indwelling catheters or condom collection systems, many who receive a diagnosis of and are treated for catheter-associated urinary tract infection (CAUTI) actually have asymptomatic bacteriuria and, therefore, that antibiotic therapy is inappropriate. METHODS: We reviewed all urine culture results at a veterans affairs medical center during a 3-month period. Cultures yielding 10(4) colony-forming units/mL were included if the urine had been collected from a hospitalized patient with an indwelling (Foley) catheter or a condom collection system. We applied standardized definitions to determine whether the episode represented catheter-associated asymptomatic bacteriuria (CAABU) or CAUTI. Antibiotic therapy was considered appropriate for patients who met criteria for symptomatic UTI. RESULTS: Overall, 280 episodes met criteria for inclusion: 164 CAABU and 116 CAUTI. Of the 164 episodes of CAABU, 111 (68%) were managed appropriately (no treatment), whereas 53 (32%) were treated with antibiotics (inappropriate treatment). In multivariate analysis, older patient age, having predominantly gram-negative bacteriuria, and higher urine white blood cell count were significantly associated with inappropriate treatment of CAABU (P < .05, by logistic regression). CONCLUSIONS: Better recognition of CAABU and the distinction between this condition and CAUTI, consistent with evidence-based guidelines, may play a key role in reducing unneeded antibiotic usage in hospitalized patients.