ABSTRACT
Mycoplasma is a well-recognised pathogen that colonises mucosal surfaces of humans and animals. Mycoplasma pneumoniae infects the upper and lower respiratory tracts of children and adults, leading to a wide range of respiratory and non-respiratory clinical conditions. M. pneumoniae infection is frequently considered in the differential diagnosis of patients with respiratory illnesses, and is commonly managed empirically with macrolides and fluoroquinolones. This contrasts with patients who present with non-respiratory symptoms in the context of a recent or current unrecognised M. pneumoniae infection, for whom this pathogen is rarely considered in the initial differential diagnosis. This review considers the microbiological, epidemiological, pathogenic and clinical features of this frequent pathogen that need to be considered in the differential diagnosis of respiratory and non-respiratory infections.
Subject(s)
Communicable Diseases, Emerging/microbiology , Mycoplasma pneumoniae/pathogenicity , Pneumonia, Mycoplasma/microbiology , Anti-Bacterial Agents/therapeutic use , Communicable Diseases, Emerging/diagnosis , Communicable Diseases, Emerging/drug therapy , Communicable Diseases, Emerging/epidemiology , Diagnosis, Differential , Humans , Mycoplasma Infections/diagnosis , Mycoplasma Infections/drug therapy , Mycoplasma Infections/epidemiology , Mycoplasma Infections/microbiology , Mycoplasma pneumoniae/immunology , Pneumonia, Mycoplasma/diagnosis , Pneumonia, Mycoplasma/drug therapy , Pneumonia, Mycoplasma/epidemiologyABSTRACT
Estrogen sulfotransferase (EST) catalyzes the transfer of the sulfuryl group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to 17beta-estradiol (E2). The sulfation of E2 prevents it from binding to, and thereby activating, the estrogen receptor. The regulation of EST appears to be causally linked to tumorigenesis in the breast and endometrium. In this study, recombinant human EST is characterized, and the catalytic mechanism of the transfer reaction is investigated in ligand binding and initial rate experiments. The native enzyme is a dimer of 35-kDa subunits. The apparent equilibrium constant for transfer to E2 is (4.5 +/- 0.2) x 10(3) at pH 6.3 and T = 25 +/- 2 degrees C. Initial rate studies provide the kinetic constants for the reaction and suggest a sequential mechanism. E2 is a partial substrate inhibitor (Ki = 80 +/- 5 nM). The binding of two E2 per EST subunit suggests that the partial inhibition occurs through binding at an allosteric site. In addition to providing the dissociation constants for the ligand-enzyme complexes, binding studies demonstrate that each substrate binds independently to the enzyme and that both the E.PAP.E2S and E.PAP.E2 dead-end complexes form. These results strongly suggest a Random Bi Bi mechanism with two dead-end complexes.
