A B S T R A C T The role of' dextrani in the pathogeniesis of' bacterial endocarditis was investigated by studying the adhereniee of' dextran producing oral streptococci to the constituenits of' nonl)acterial thrombotic endocarditis (NBTE) in vitro and in vivo. The adherence of' Streptococcus saniguis to fibrin and platelets was determinedl in an in vitro assay system simulating non-I)acterial thrombotic endocarditis. Adherence was increased when the organismiis were grown in sucrosesuipplemented media (adherence ratio x 104, 177+6 in 5% suicrose vs. 140±7 in 0.5% sucrose, P < 0.001), and decreased by incubating the organisms in dextranase (adherence ratio x 104, 117+ 16, P < 0.001), an effect which was nullified by heat inactivating this enzyme (adherence ratio x 104, 192+7, P < 0.001). The amount of dextran produced in broth by three different oral streptococci correlated directly with the adherence observed to fibrin and a fibrin-platelet matrix in vitro (P < 0.001). These organisms adhered more readily to a fibrin-platelet matrix than to fibrin alone (adherence ratio x 104, 455±30 vs. 177±6, respectively, P < 0.001).The role of dextran formation was also examined in vivo in rabbits with preexisting NBTE. After injection of 107 S. sangguis, 12 of 17 animals developed endocarditis. In contrast, when the organisms were pretreated with dextranase (an enzyme that removes dextran from the bacterial cell surface), the same inoculum resulted in endocarditis in only 5 of' 19 animals (P < 0.05). In addition, a fresh strain of' S. sanguis that produiced high levels of dextran (1,220+50 ,Ag/ml) and adhered avidly to fibrin (adherence ratio x 104, 220 ±11) prodtuced endocarditis in 12 of' 18 rabbits after injection of 107 organisms. Another isolate of the same

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In Neurospora crassa, evidence has recently been obtained for a cluster of four closely-linked genes controlling the inducible enzymes catalyzing the first three reactions in the catabolism of quinic acid. Three of these genes appear to be the structural genes for the three enzymes. The fourth gene, designated qa-1, has been interpreted as having a regulatory function, since qa-) mutants are pleiotropic types, are noninducible for the three enzymes, and form heterocaryons which complement mutants in the structural genes. The present studies were undertaken to elucidate further the nature of the regulatory role of the qa-) locus. A number of constitutive (qa-1C) mutants (3,4) have reported that the regulatory gene for the galactose system of Saccharomyces cerevisiae is unlinked to the cluster of three structural genes and, furthermore, that no evidence exists for an operator region adjacent to this cluster. Also, although there is evidence that the arom gene cluster in Neurospora crassa has certain operon-like characteristics, such as polarized transcription, again no clear evidence has been obtained for an adjacent operator or promoter region (5). Recent work by Rines (6,8) on the quinic acid catabolic pathway of Neurospora crassa has suggested the occurrence of a regulatory gene, qa-1, controlling the expression of the first three enzymatic activities in the pathway. This qa-1 gene is closely linked to the structural gene, qa-2, which encodes one of the activities, catabolic dehydroquinase (5-dehydroquinate dehydratase, EC 4.2.1.10) (9). Very recent evidence also indicates that the structural genes for the other two enzymes, qa-3, encoding quinate dehydrogenase (quinate: NAD oxidoreductase, EC 1.1.1.24) and qa-4, encoding 5-dehydroshikimate dehydrase, are also closely linked to the qa-1 locus (7). Rines (8) has suggested that the regulatory locus, qa-1, might resemble an operontype system in producing a regulatory protein which controls the synthesis of the three structural gene products. However, alternative models were also considered. For example, the qa-1 gene might encode an enzyme which converts the presumed inducer (dehydroquinic acid) into the actual, as yet unknown, inducer or the locus might produce a polypeptide common to all three structural gene products and necessary for all their activities.Acting on the hypothesis that the wild-type qa-1 + locus produces a regulatory protein necessary to initiate synthesis of the first three enzymes in quinate catabolism, we have sought to recover qa-1 mutants constitutive for the enzymes encoded in the three structural genes. These types have been sought among revertants of various qa-1 mutants (which are pleiotropic mutants, noninducible for all three enzymes) for which revertant selection has occurred on medium containing quinic acid as a sole carbon source. This paper presents evidence for the recovery of such constitutive mutants (qa-1C) in Neurospora and a preliminary characterization of these mutants in terms of the magnitude of their catabolic...