Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 May 12:12:832254.
doi: 10.3389/fcimb.2022.832254. eCollection 2022.

Pneumococcal Surface Proteins as Virulence Factors, Immunogens, and Conserved Vaccine Targets

Javid Aceil  1 , Fikri Y Avci  1
Affiliations
Review

Pneumococcal Surface Proteins as Virulence Factors, Immunogens, and Conserved Vaccine Targets

Javid Aceil et al. Front Cell Infect Microbiol. .

Abstract

Streptococcus pneumoniae is an opportunistic pathogen that causes over 1 million deaths annually despite the availability of several multivalent pneumococcal conjugate vaccines (PCVs). Due to the limitations surrounding PCVs along with an evolutionary rise in antibiotic-resistant and unencapsulated strains, conserved immunogenic proteins as vaccine targets continue to be an important field of study for pneumococcal disease prevention. In this review, we provide an overview of multiple classes of conserved surface proteins that have been studied for their contribution to pneumococcal virulence. Furthermore, we discuss the immune responses observed in response to these proteins and their promise as vaccine targets.

Keywords: CbpA; PhtD pneumococcal histidine triad protein D; PspA; PsrP; Streptoccoccus pneumoniae; conjugate vaccine; pneumococcal protein vaccine; pneumolysin (PLY).

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Interactions of pneumococcal factors representative of classes within the host respiratory epithelium. (A) PLY is released from Spn. It is pro-inflammatory in the environment and PLY monomers aggregate to form ring complexes that can trigger host cell death. It can interact with MRC-1 to promote bacterial survival. (B) CBPs impair complement-mediated killing by the host. PcpA influences biofilm formation and pneumococcal adhesion. CbpA binds its main receptor, pIgR, to promote adherence. PspA binds lactoferrin for critical iron uptake for the bacterium from the host and inhibits apolactoferrin. Both CbpA and PspA can bind lactate dehydrogenase to enhance virulence. (C) The PHTs are well-conserved surface proteins on the pneumococcus and maintain metal homeostasis through Zn and Ni binding. (D) A model showing PsrP’s SRR1-BR region extending past the CPS. While the SRR1 glycans potentially interact with another host ligand (1), the basic region binds Keratin-10 (2). Alternatively, as previously hypothesized, the glycans may be employed as important interactors with the CPS to hoist PsrP up so that it can extend past the capsule (3).
See this image and copyright information in PMC

References

    1. Adamou J. E., Heinrichs J. H., Erwin A. L., Walsh W., Gayle T., Dormitzer M., et al. . (2001). Identification and Characterization of a Novel Family of Pneumococcal Proteins That are Protective Against Sepsis. Infect. Immun. doi: 10.1128/IAI.69.2.949-958.2001 - DOI - PMC - PubMed
    1. Afshar D., Pourmand M. R., Jeddi-Tehrani M., Saboor Yaraghi A. A., Azarsa M., Shokri F. (2016). Fibrinogen and Fibronectin Binding Activity and Immunogenic Nature of Choline Binding Protein M. Iran J. Public Health 45, 1610–1617. - PMC - PubMed
    1. Alexander J. E., Lock R. A., Peeters C. C., Poolman J. T., Andrew P. W., Mitchell T. J., et al. . (1994). Immunization of Mice With Pneumolysin Toxoid Confers a Significant Degree of Protection Against at Least Nine Serotypes of Streptococcus Pneumoniae. Infect. Immun. 62, 5683–5688. doi: 10.1128/iai.62.12.5683-5688.1994 - DOI - PMC - PubMed
    1. Anderson R., Feldman C. (2017). Pneumolysin as a Potential Therapeutic Target in Severe Pneumococcal Disease. J. Infect. 74, 527–544. doi: 10.1016/j.jinf.2017.03.005 - DOI - PubMed
    1. Andre G. O., Borges M. T., Assoni L., Ferraz L. F. C., Sakshi P., Adamson P., et al. . (2021). Protective Role of PhtD and its Amino and Carboxyl Fragments Against Pneumococcal Sepsis. Vaccine 39, 3626–3632. doi: 10.1016/j.vaccine.2021.04.068 - DOI - PubMed

Publication types

LinkOut - more resources