Zinc uptake by Streptococcus pneumoniae depends on both AdcA and AdcAII and is essential for normal bacterial morphology and virulence

Abstract

Zinc is an essential trace metal for living cells. The ABC transporter AdcABC was previously shown to be required for zinc uptake by Streptococcus pneumoniae. As we have recently described AdcAII as another zinc-binding lipoprotein, we have investigated the role of both AdcA and AdcAII in S. pneumoniae zinc metabolism. Deletion of either adcA or adcAII but not phtD reduced S. pneumoniae zinc uptake, with dual mutation of both adcA and adcAII further decreasing zinc import. For the Δ(adcA/adcAII) mutant, growth and intracellular concentrations of zinc were both greatly reduced in low zinc concentration. When grown in zinc-deficient medium, the Δ(adcA/adcAII) mutant displayed morphological defects related to aberrant septation. Growth and morphology of the Δ(adcA/adcAII) mutant recovered after supplementation with zinc. Dual deletion of adcA and adcAII strongly impaired growth of the pneumococcus in bronchoalveolar lavage fluid and human serum, and prevented S. pneumoniae establishing infection in mouse models of nasopharyngeal colonization, pneumonia and sepsis without altering the capsule. Taken together, our results show that AdcA and AdcAII play an essential and redundant role in specifically importing zinc into the pneumococcus, and that both zinc transporters are required for proper cell division and for S. pneumoniae survival during infection.