Deletion ofarcDin Streptococcus pneumoniae D39 Impairs Its Capsule and Attenuates Virulence

Abstract

ABSTRACTThe arginine deiminase system (ADS) is associated with arginine catabolism and plays a role in virulence of several pathogenic bacteria. InStreptococcus pneumoniae, the ADS genes exist as a locus consisting ofarcABCDT. A recent genome-wide mutagenesis approach revealed that botharcDandarcTare potentially essential in a chinchilla otitis media (OM) model. In the present study, we generated ΔarcD, ΔarcT, and ΔarcDTmutants by homologous recombination and evaluated their infectivity. Our results showed that onlyarcD, and notarcT, of an OM isolate is required during chinchilla middle ear infection. Additionally, D39 ΔarcDexhibited enhanced nasopharyngeal colonization and was attenuated in both mouse pneumonia and bacteremia models.In vitro, D39 ΔarcDdisplayed enhanced adherence to A549 epithelial cells and increased phagocytosis by J774A.1 macrophages compared to those with the parental strain. This mutant also exhibited an impaired capsule, as detected using electron microscopy, immunofluorescence, and a capsule assay. We demonstrated that the capsule defect in the D39 ΔarcDmutant may not be associated with a deficiency in arginine but rather is likely caused by a loss of interaction between the capsule and the transmembrane protein ArcD.