Structure of CfaA suggests a new family of chaperones essential for assembly of class 5 fimbriae.

Adhesive pili on the surface of pathogenic bacteria comprise polymerized pilin subunits and are essential for initiation of infections. Pili assembled by the chaperone-usher pathway (CUP) require periplasmic chaperones that assist subunit folding, maintain their stability, and escort them to the site of bioassembly. Until now, CUP chaperones have been classified into two families, FGS and FGL, based on the short and long length of the subunit-interacting loops between its F1 and G1 ß-strands, respectively. CfaA is the chaperone for assembly of colonization factor antigen I (CFA/I) pili of enterotoxigenic E. coli (ETEC), a cause of diarrhea in travelers and young children. Here, the crystal structure of CfaA along with sequence analyses reveals some unique structural and functional features, leading us to propose a separate family for CfaA and closely related chaperones. Phenotypic changes resulting from mutations in regions unique to this chaperone family provide insight into their function, consistent with involvement of these regions in interactions with cognate subunits and usher proteins during pilus assembly.

Taste and smell function in chronic disease: a review of clinical and biochemical evaluations of taste and smell dysfunction in over 5000 patients at The Taste and Smell Clinic in Washington, DC.

PURPOSE: To describe systematic methods developed over 40 years among over 5000 patients at The Taste and Smell Clinic in Washington, DC to evaluate taste and smell dysfunction. MATERIALS AND METHODS: A tripartite methodology was developed. First, methods to determine clinical pathology underlying the multiple disease processes responsible for taste and smell dysfunction were developed. Second, methods to determine biochemical parameters responsible for these pathologies were developed. Third, methods to implement these techniques were developed to form a unified basis upon which treatment strategies can be developed to treat these patients. RESULTS: Studies were performed in 5183 patients. Taste loss was present in 62% of patients, smell loss in 87%. Most patients with taste loss (52%) exhibited Type II hypogeusia; most patients with smell loss (56%) exhibited Type II hyposmia. Sensory distortions were present in 60%. Four common diagnostic entities were found: post influenza-type hyposmia and hypogeusia (27% of patients), idiopathic causes (16%), allergic rhinitis (15%) and post head injury (14%). Regardless of clinical diagnosis the major biochemical abnormality found in most patients (~70%) was diminished parotid salivary and nasal mucus secretion of cAMP and cGMP. CONCLUSIONS: Taste and smell dysfunctions are common clinical problems associated with chronic disease processes. These symptoms require a systematic, integrated approach to understand their multiple and complex components. The approach presented here can and has led to effective treatment.

Distinguishing patients with glossopyrosis from those with oropyrosis based upon clinical differences and differences in saliva and erythrocyte magnesium.

OBJECTIVE: Burning mouth syndrome (BMS) is a complex of clinical symptoms defined by burning sensations in the oral cavity without observed oral pathology. Clinically two patient groups within BMS were distinguished, one with burning limited to the anterior tongue (glossopyrosis) and the other with burning in multiple mouth regions, including tongue, lips, palate, gums and cheeks (oropyrosis). Biochemical differences between these two groups could assist in distinguishing them. DESIGN: Eighty-three patients with BMS, 47 with oropyrosis and 31 with glossopyrosis were studied. Measurements of zinc, copper, magnesium and calcium in blood plasma, erythrocytes and parotid saliva were obtained in patients and in normal subjects and mean levels were compared. RESULTS: Clinical history differentiated patients into categories of oropyrosis and glossopyrosis. Erythrocyte and saliva levels of magnesium were significantly lower in patients with glossopyrosis than in patients with oropyrosis or in normal volunteers whereas levels of zinc and calcium were similar. CONCLUSIONS: These data suggest that patients with glossopyrosis not only differ clinically from those with oropyrosis but also exhibit magnesium deficiency as manifested by lower than normal magnesium levels in saliva and erythrocytes. Lingual burning in patients with glossopyrosis is consistent with hyperalgesia and neurogenic inflammation observed in patients and animals with magnesium deficiency and in magnesium deficient tissues. These results suggest a possible biochemical mechanism for pyrosis in patients with glossopyrosis.