Affiliation:
1. Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294
Abstract
ABSTRACT
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
64 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献