Duplication of Teichoic Acid Biosynthetic Genes in
Staphylococcus aureus
Leads to Functionally Redundant Poly(Ribitol Phosphate) Polymerases
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abstract
ABSTRACT
Wall teichoic acids are anionic phosphate-rich polymers that are part of the complex meshwork of carbohydrates that make up the gram-positive cell wall. These polymers are essential to the proper rod-shaped morphology of
Bacillus subtilis
and have been shown to be an important virulence determinant in the nosocomial opportunistic pathogen
Staphylococcus aureus
. Together, sequence-based studies, in vitro experiments with biosynthetic proteins, and analyses of the chemical structure of wall teichoic acid have begun to shed considerable light on our understanding of the biogenesis of this polymer. Nevertheless, some paradoxes remain unresolved. One of these involves a putative duplication of genes linked to CDP-ribitol synthesis (
tarI
′
J
′ and
tarIJ
) as well as poly(ribitol phosphate) polymerization (
tarK
and
tarL
) in
S. aureus
. In the work reported here, we performed careful studies of the dispensability of each gene and discovered a functional redundancy in the duplicated gene clusters. We were able to create mutants in either of the putative ribitol phosphate polymerases (encoded by
tarK
and
tarL
) without affecting teichoic acid levels in the
S. aureus
cell wall. Although genes linked to CDP-ribitol synthesis are also duplicated, a null mutant in only one of these (
tarI
′
J
′) could be obtained, while
tarIJ
remained essential. Suppression analysis of the
tarIJ
null mutant indicated that the mechanism of dysfunction in
tarI
′
J
′ is due to poor translation of the TarJ′ enzyme, which catalyzes the rate-limiting step in CDP-ribitol formation. This work provides new insights into understanding the complex synthetic steps of the ribitol phosphate polymer in
S. aureus
and has implications on specifically targeting enzymes involved in polymer biosynthesis for antimicrobial design.
