Immunization with Polyamine Transport Protein PotD Protects Mice against Systemic Infection with Streptococcus pneumoniae

Abstract

The human pathogen Streptococcus pneumoniae contains genes for a putative polyamine ABC transporter which are organized in an operon and designated potABCD. Polyamine transport protein D (PotD) is an extracellular protein which binds polyamines and possibly other structurally related molecules. PotD has been shown to contribute to virulence in both a murine sepsis model and a pneumonia model with capsular type 3 pneumococci. The protective efficacy of recombinant PotD was evaluated by active immunization and intravenous challenge with capsular type 3 pneumococci in CBA/N mice. Immunized mice had 91.7% survival following lethal pneumococcal challenge, compared with 100% mortality in the control group. Immunized animals had high-titer anti-PotD antibodies following three immunizations with alum. Protection in a sepsis model was also seen after passive administration of rabbit antiserum raised against PotD (P < 0.004). These results suggest that antibodies to PotD confer protection against invasive pneumococcal disease and that this protein should be studied further as a potential vaccine candidate for protection against invasive pneumococcal infections.

Identification of a LolC Homologue inBurkholderia pseudomallei, a Novel Protective Antigen for Melioidosis

“…In E. coli, disruption of lolC is lethal and prevents the release of lipoproteins from the inner membrane (26). PotF is a periplasmic binding protein of the PotFGHI system involved in putrescine import in E. coli (31), a system that has homologues required for attachment to plant cells and for full virulence in the phytopathogen Agrobacterium tumefaciens (24). Finally, OppA is an oligopeptide-binding protein of the Opp system in E. coli (14).…”

“…ABC system proteins were selected as potential vaccine candidates because members of this family of proteins have been shown generally to be immunogenic and to play roles in bacterial virulence (16). In addition, some components of ABC systems have been shown to be vaccine antigens (6,31,34,35). Homologues of the LolC, PotF, and OppA proteins identified in B. pseudomallei and soluble domains were produced in E. coli, with membrane-spanning regions removed in order to aid expression and purification for the study.…”

“…Indeed, ABC system proteins that are immu-noreactive with convalescent-phase sera have been identified in both gram-positive and gram-negative bacteria (16). Furthermore, an increasing number of ABC system proteins are being considered as candidate vaccine antigens (6,31,34,35).…”

Recent Advances in Bacterial Polyamine Transport Systems

“…Additionally, proteomics analysis revealed that the secretion of PotD into environment is correlated with the formation of biofi lms in Aggregatibacter actinomycetemcomitans , causing aggressive periodontitis (Zijnge et al 2012 ). Furthermore, Shah and Swiatlo et al reported that in Streptococcus pneumoniae , which causes pneumonia, uptake of spermidine by PotABCD is important for pathogenicity in mice, and an antiPotD antibody was used in a study of infection control of S. pneumoniae (Shah and Swiatlo 2006 ). In uropathogenic Proteus mirabilis PlaP is important for putrescine uptake, swarming motility, and urothelial cell invasion.…”

Spermidine Biosynthesis and Transport Modulate Pneumococcal Autolysis

“…Although the importance of polyamine biosynthesis and transport in pneumococcal pathogenesis has been known for a number of years (15,16,31), the precise molecular role of these molecules in this important bacterial pathogen has remained elusive. We have demonstrated that pneumococci encode enzymes for the synthesis of spermidine from arginine.…”