Targeted Transcriptomic Screen of Pneumococcal Genes Expressed during Murine and Human Infection.

Basset, Alan, Wall, Emma, Mitsi, Elena, Deshusses, Chloe, Daly, Raecliffe, Pojar, Sherin ORCID: https://orcid.org/0000-0002-7746-3279, Reiné, Jesús, Guerra-Assuncao, Jose Afonso, Denis, Brigitte, Jochems, Simon ORCID: https://orcid.org/0000-0002-4835-1032, Heyderman, Robert, Brown, Jeremy, Lu, Ying-Jie, Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902 and Malley, Richard (2022) 'Targeted Transcriptomic Screen of Pneumococcal Genes Expressed during Murine and Human Infection.'. Infection and immunity, Vol 90, Issue 7, e0017522.

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Abstract

The advent of pneumococcal conjugate vaccines led to the near disappearance of most of the included serotypes in high-income settings but also the rise of nonvaccine-type colonization and disease. Alternative strategies, using genetically conserved proteins as antigens, have been evaluated preclinically and clinically for years, so far unsuccessfully. One possible explanation for the failure of these efforts is that the choice of antigens may not have been sufficiently guided by an understanding of the gene expression pattern in the context of infection. Here, we present a targeted transcriptomic analysis of 160 pneumococcal genes encoding bacterial surface-exposed proteins in mouse models, human colonization, and human meningitis. We present the overlap of these different transcriptomic profiles. We identify two bacterial genes that are highly expressed in the context of mouse and human infection: SP_0282, an IID component of a mannose phosphotransferase system (PTS), and SP_1739, encoding RNase Y. We show that these two proteins can confer protection against pneumococcal nasopharyngeal colonization and intraperitoneal challenge in a murine model and generate opsonophagocytic antibodies. This study emphasizes and confirms the importance of studies of pneumococcal gene expression of bacterial surface proteins during human infection and colonization and may pave the way for the selection of a protein-based vaccine candidate.

Item Type:	Article
Subjects:	QU Biochemistry > Genetics > QU 460 Genomics. Proteomics WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 204 Pneumococcal pneumonia. Staphylococcal pneumonia WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1128/iai.00175-22
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	24 Nov 2022 12:00
Last Modified:	30 Aug 2023 14:05
URI:	https://archive.lstmed.ac.uk/id/eprint/20633

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