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Infection and Immunity, April 2001, p. 2309-2317, Vol. 69, No. 4
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.4.2309-2317.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Essential Role for Cellular Phosphoglucomutase in
Virulence of Type 3 Streptococcus
pneumoniae
Gail G.
Hardy,
Ashalla D.
Magee,
Christy L.
Ventura,
Melissa J.
Caimano,
and
Janet
Yother*
Department of Microbiology, University of
Alabama at Birmingham, Birmingham, Alabama 35294
Received 6 December 2000/Returned for modification 8 January
2001/Accepted 15 January 2001
Synthesis of the Streptococcus pneumoniae type 3 capsule requires the pathway glucose-6-phosphate (Glc-6-P)
Glc-1-P
UDP-Glc
UDP-glucuronic acid (UDP-GlcUA)
(GlcUA-Glc)n. The UDP-Glc dehydrogenase and
synthase necessary for the latter two steps, and essential for capsule
production, are encoded by genes (cps3D and
cps3S, respectively) located in the type 3 capsule locus. The phosphoglucomutase (PGM) and Glc-1-P
uridylyltransferase activities necessary for the first two steps are
derived largely through the actions of cellular enzymes. Homologues of
these enzymes, encoded by cps3M and cps3U
in the type 3 locus, are not required for capsule production. Here, we
show that cps3M and cps3U also are not
required for mouse virulence. In contrast, nonencapsulated isolates
containing defined mutations in cps3D and
cps3S were avirulent, as were reduced-capsule isolates
containing mutations in pgm. Insertion mutants that
lacked PGM activity were avirulent in both immunologically normal
(BALB/cByJ) and immunodeficient (CBA/N) mice. In contrast, a mutant
(JY1060) with reduced PGM activity was avirulent in the former but had
only modestly reduced virulence in the latter. The high virulence in
CBA/N mice was not due to the lack of antibodies to phosphocholine but
reflected a growth environment distinct from that found in BALB/cByJ
mice. The reduced PGM activity of JY1060 resulted in enhanced binding of complement and antibodies to surface antigens. However,
decomplementation of BALB/cByJ mice did not enhance the virulence of
this mutant. Suppressor mutations, only some of which resulted in
increased capsule production, increased the virulence of JY1060 in
BALB/cByJ mice. The results suggest that PGM plays a critical role in
pneumococcal virulence by affecting multiple cellular pathways.
*
Corresponding author. Mailing address: Department of
Microbiology, BBRB 661, 845 19th St. S., University of Alabama at
Birmingham, Birmingham, AL 35294. Phone: (205) 934-9531. Fax: (205)
975-6715. E-mail: jyother{at}uab.edu.

Present address: Department of Pediatrics, Washington University,
St. Louis, MO
63110.

Present address: Center for Microbial Pathogenesis, University of
Connecticut Health Center, Farmington, CT
06030.
Infection and Immunity, April 2001, p. 2309-2317, Vol. 69, No. 4
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.4.2309-2317.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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