Deletion of arcD in Streptococcus pneumoniae D39 Impairs Its Capsule and Attenuates Virulence

Abstract

The arginine deiminase system (ADS) is associated with arginine catabolism and plays a role in virulence of several pathogenic bacteria. In Streptococcus pneumoniae, the ADS genes exist as a locus consisting of arcABCDT. A recent genome-wide mutagenesis approach revealed that both arcD and arcT are potentially essential in a chinchilla otitis media (OM) model. In the present study, we generated ⌬arcD, ⌬arcT, and ⌬arcDT mutants by homologous recombination and evaluated their infectivity. Our results showed that only arcD, and not arcT, of an OM isolate is required during chinchilla middle ear infection. Additionally, D39 ⌬arcD exhibited enhanced nasopharyngeal colonization and was attenuated in both mouse pneumonia and bacteremia models. In vitro, D39 ⌬arcD displayed 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 ⌬arcD mutant 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.

Streptococcus pyogenes Arginine and Citrulline Catabolism Promotes Infection and Modulates Innate Immunity

“…One possible explanation for this hyperattenutation could be the disruption of a secondary function of ArcB that resides outside arginine catabolism. Recently it has been demonstrated that deletion of arcD in S. pneumoniae has a negative impact on pathogenesis independent of its canonical function within the ADI pathway (39). However, given that deletion of arcC in S. pyogenes downstream of arcB was also hyperattenuated in the cutaneous model, the data presented are more consistent with a tissue-specific requirement for citrulline metabolism.…”

Panel 4: Report of the Microbiology Panel

“…95 A mutation in the gene encoding the arginine transporter ArcD caused a reduction in capsule production and ability to cause OM in a chinchilla model, likely due to differences in the surface association of capsule. 96 A study demonstrated that a laboratory-generated capsular switch led to increased pathogenesis in a chinchilla barotrauma model of AOM. 93 In another barotrauma model of OM, serotype 6C strains showed reduced ability to produce ME disease as compared with serotype 19A isolates.…”

Identification and analysis of genomic islands in Burkholderia cenocepacia AU 1054 with emphasis on pathogenicity islands

“…A bacterial adhesion assay was performed as previously described with slight modification [41, 42]. Briefly, A549 cells were seeded into 24-well tissue culture plates at 2 × 10 5 cells per well and incubated at 37 °C with 5% CO 2 for 24 h before infection.…”