The has operon is composed of three genes, hasA, hasB, and hasC that encode hyaluronate synthase, UDP-glucose dehydrogenase, and presumptively UDP-glucose pyrophosphorylase, respectively. Expression of the has operon was shown to be required for the synthesis of the hyaluronic acid capsule in group A streptococci. Previous studies indicated that some group A and group C streptococcal strains produce the hyaluronic acid capsule, while others do not. In addition, it was observed that encapsulated strains cultured in stationary phase of growth lose the hyaluronic acid capsule. Therefore, the molecular mechanisms controlling the expression of the hyaluronic acid capsule in group A streptococci was investigated. In this study, it was determined that all encapsulated and unencapsulated strains of group A streptococci as well as encapsulated group C streptococci analyzed possess the has operon locus. The acapsular phenotype was accounted for by the absence of hyaluronate synthase activity in the membrane and not the production of extracellular hyaluronidase. A has operon mRNA transcript was not expressed by unencapsulated strains of group A streptococci, whereas encapsulated strains of group A streptococci grown to mid to late exponential phase produced the hyaluronate capsule, as well as has operon mRNA. However, as the streptococci entered the stationary phase of growth, they became acapsular and this was concomitant with the loss of has operon mRNA transcript. These results were confirmed by primer extension analyses of RNA isolated from encapsulated and unencapsulated strains of group A streptococci as well as RNA prepared from encapsulated strains cultured in exponential and stationary phases of growth. Thus, the loss of has operon mRNA in unencapsulated group A streptococci, as well as growth phase regulation occurs at the previously mapped has operon promoter. These data suggested that the synthesis of the hyaluronic acid capsule for group A streptococci may be controlled by transcriptional mechanisms.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				R.-J. Hung, H.-S. Chien, R.-Z. Lin, C.-T. Lin, J. Vatsyayan, H.-L. Peng, and H.-Y. Chang Comparative Analysis of Two UDP-glucose Dehydrogenases in Pseudomonas aeruginosa PAO1 J. Biol. Chem., June 15, 2007; 282(24): 17738 - 17748. [Abstract] [Full Text] [PDF]

				B. Widner, R. Behr, S. Von Dollen, M. Tang, T. Heu, A. Sloma, D. Sternberg, P. L. DeAngelis, P. H. Weigel, and S. Brown Hyaluronic Acid Production in Bacillus subtilis Appl. Envir. Microbiol., July 1, 2005; 71(7): 3747 - 3752. [Abstract] [Full Text] [PDF]

				L. E. Hancock, B. D. Shepard, and M. S. Gilmore Molecular Analysis of the Enterococcus faecalis Serotype 2 Polysaccharide Determinant J. Bacteriol., August 1, 2003; 185(15): 4393 - 4401. [Abstract] [Full Text] [PDF]

				S. Dobinsky, K. Kiel, H. Rohde, K. Bartscht, J. K.-M. Knobloch, M. A. Horstkotte, and D. Mack Glucose-Related Dissociation between icaADBC Transcription and Biofilm Expression by Staphylococcus epidermidis: Evidence for an Additional Factor Required for Polysaccharide Intercellular Adhesin Synthesis J. Bacteriol., May 1, 2003; 185(9): 2879 - 2886. [Abstract] [Full Text] [PDF]

				J. Jadoun, O. Eyal, and S. Sela Role of CsrR, Hyaluronic Acid, and SpeB in the Internalization of Streptococcus pyogenes M Type 3 Strain by Epithelial Cells Infect. Immun., February 1, 2002; 70(2): 462 - 469. [Abstract] [Full Text] [PDF]

				M. S. Chaussee, G. L. Sylva, D. E. Sturdevant, L. M. Smoot, M. R. Graham, R. O. Watson, and J. M. Musser Rgg Influences the Expression of Multiple Regulatory Loci To Coregulate Virulence Factor Expression in Streptococcus pyogenes Infect. Immun., February 1, 2002; 70(2): 762 - 770. [Abstract] [Full Text] [PDF]

				P. L. DeAngelis Microbial glycosaminoglycan glycosyltransferases Glycobiology, January 1, 2002; 12(1): 9R - 16R. [Abstract] [Full Text] [PDF]

				P. N. Ward, T. R. Field, W. G. F. Ditcham, E. Maguin, and J. A. Leigh Identification and Disruption of Two Discrete Loci Encoding Hyaluronic Acid Capsule Biosynthesis Genes hasA, hasB, and hasC in Streptococcus uberis Infect. Immun., January 1, 2001; 69(1): 392 - 399. [Abstract] [Full Text] [PDF]

				M. W. Cunningham Pathogenesis of Group A Streptococcal Infections Clin. Microbiol. Rev., July 1, 2000; 13(3): 470 - 511. [Abstract] [Full Text] [PDF]

				G. G. Hardy, M. J. Caimano, and J. Yother Capsule Biosynthesis and Basic Metabolism in Streptococcus pneumoniae Are Linked through the Cellular Phosphoglucomutase J. Bacteriol., April 1, 2000; 182(7): 1854 - 1863. [Abstract] [Full Text]

				G. L. Darmstadt, L. Mentele, A. Podbielski, and C. E. Rubens Role of Group A Streptococcal Virulence Factors in Adherence to Keratinocytes Infect. Immun., March 1, 2000; 68(3): 1215 - 1221. [Abstract] [Full Text] [PDF]

				A. Heath, V. J. DiRita, N. L. Barg, and N. C. Engleberg A Two-Component Regulatory System, CsrR-CsrS, Represses Expression of Three Streptococcus pyogenes Virulence Factors, Hyaluronic Acid Capsule, Streptolysin S, and Pyrogenic Exotoxin B Infect. Immun., October 1, 1999; 67(10): 5298 - 5305. [Abstract] [Full Text] [PDF]

				M. Unnikrishnan, J. Cohen, and S. Sriskandan Growth-Phase-Dependent Expression of Virulence Factors in an M1T1 Clinical Isolate of Streptococcus pyogenes Infect. Immun., October 1, 1999; 67(10): 5495 - 5499. [Abstract] [Full Text] [PDF]

				M. J. Federle, K. S. McIver, and J. R. Scott A Response Regulator That Represses Transcription of Several Virulence Operons in the Group A Streptococcus J. Bacteriol., June 15, 1999; 181(12): 3649 - 3657. [Abstract] [Full Text]

				B. Bernish and I. van de Rijn Characterization of a Two-component System in Streptococcus pyogenes Which Is Involved in Regulation of Hyaluronic Acid Production J. Biol. Chem., February 19, 1999; 274(8): 4786 - 4793. [Abstract] [Full Text] [PDF]

				V. L. Tlapak-Simmons, B. A. Baggenstoss, K. Kumari, C. Heldermon, and P. H. Weigel Kinetic Characterization of the Recombinant Hyaluronan Synthases from Streptococcus pyogenes and Streptococcus equisimilis J. Biol. Chem., February 12, 1999; 274(7): 4246 - 4253. [Abstract] [Full Text] [PDF]

				M. Mollerach, R. Lopez, and E. Garcia Characterization of the galU Gene of Streptococcus pneumoniae Encoding a Uridine Diphosphoglucose Pyrophosphorylase: A Gene Essential for Capsular Polysaccharide Biosynthesis J. Exp. Med., December 7, 1998; 188(11): 2047 - 2056. [Abstract] [Full Text] [PDF]

				V. L. Tlapak-Simmons, E. S. Kempner, B. A. Baggenstoss, and P. H. Weigel The Active Streptococcal Hyaluronan Synthases (HASs) Contain a Single HAS Monomer and Multiple Cardiolipin Molecules J. Biol. Chem., October 2, 1998; 273(40): 26100 - 26109. [Abstract] [Full Text] [PDF]

				P. L. DeAngelis, W. Jing, R. R. Drake, and A. M. Achyuthan Identification and Molecular Cloning of a Unique Hyaluronan Synthase from Pasteurella multocida J. Biol. Chem., April 3, 1998; 273(14): 8454 - 8458. [Abstract] [Full Text] [PDF]

				A. P. Spicer and J. A. McDonald Characterization and Molecular Evolution of a Vertebrate Hyaluronan Synthase Gene Family J. Biol. Chem., January 23, 1998; 273(4): 1923 - 1932. [Abstract] [Full Text] [PDF]

				R. E. Campbell, R. F. Sala, I. van de Rijn, and M. E. Tanner Properties and Kinetic Analysis of UDP-glucose Dehydrogenase from Group A Streptococci. IRREVERSIBLE INHIBITION BY UDP-CHLOROACETOL J. Biol. Chem., February 7, 1997; 272(6): 3416 - 3422. [Abstract] [Full Text] [PDF]

				A. M. Shyjan, P. Heldin, E. C. Butcher, T. Yoshino, and M. J. Briskin Functional Cloning of the cDNA for a Human Hyaluronan Synthase J. Biol. Chem., September 20, 1996; 271(38): 23395 - 23399. [Abstract] [Full Text] [PDF]

				D. L. Crater, B. A. Dougherty, and I. van de Rijn Molecular Characterization of hasC from an Operon Required for Hyaluronic Acid Synthesis in Group A Streptococci J. Biol. Chem., December 1, 1995; 270(48): 28676 - 28680. [Abstract] [Full Text] [PDF]