Prevalence and Homology of the Pneumococcal Serine-Rich Repeat Protein at the Global Scale.
Prevalence and Homology of the Pneumococcal Serine-Rich Repeat Protein at the Global Scale.
复制标题
全球范围内肺炎球菌富含丝氨酸重复蛋白的流行率和同源性。
DOI:
10.1128/spectrum.03252-22
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发表时间:
2023-06-15
影响因子:
3.7
通讯作者:
中科院分区:
文献类型:
--
作者:
Pneumococcal pneumonia remains a WHO high-priority disease despite multivalent conjugate vaccines administered in clinical practice worldwide. A protein-based, serotype-independent vaccine has long-promised comprehensive coverage of most clinical isolates of the pneumococcus. Along with numerous pneumococcal surface protein immunogens, the pneumococcal serine-rich repeat protein (PsrP) has been investigated as a potential vaccine target due to its surface exposure and functions toward bacterial virulence and lung infection. Three critical criteria for its vaccine potential — the clinical prevalence, serotype distribution, and sequence homology of PsrP — have yet to be well characterized. Here, we used genomes of 13,454 clinically isolated pneumococci from the Global Pneumococcal Sequencing project to investigate PsrP presence among isolates, distribution among serotypes, and interrogate its homology as a protein across species. These isolates represent all age groups, countries worldwide, and types of pneumococcal infection. We found PsrP present in at least 50% of all isolates across all determined serotypes and nontypeable (NT) clinical isolates. Using a combination of peptide matching and HMM profiles built on full-length and individual PsrP domains, we identified novel variants that expand PsrP diversity and prevalence. We also observed sequence variability in its basic region (BR) between isolates and serotypes. PsrP has a strong vaccine potential due to its breadth of coverage, especially in nonvaccine serotypes (NVTs) when exploiting its regions of conservation in vaccine design. IMPORTANCE An updated outlook on PsrP prevalence and serotype distribution sheds new light on the comprehensiveness of a PsrP-based protein vaccine. The protein is present in all vaccine serotypes and highly present in the next wave of potentially disease-causing serotypes not included in the current multivalent conjugate vaccines. Furthermore, PsrP is strongly correlated with clinical isolates harboring pneumococcal disease as opposed to pneumococcal carriage. PsrP is also highly present in strains and serotypes from Africa, where the need for a protein-based vaccine is the greatest, giving new reasoning to pursue PsrP as a protein vaccine.
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影响因子:
3.7
作者:
Jurtz VI;Villarroel J;Lund O;Voldby Larsen M;Nielsen M
通讯作者:
Nielsen M
影响因子:
64.8
作者:
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者:
Hassabis D
影响因子:
6.2
作者:
Pichichero ME
通讯作者:
Pichichero ME
影响因子:
14.9
作者:
Mistry J;Finn RD;Eddy SR;Bateman A;Punta M
通讯作者:
Punta M
影响因子:
7.8
作者:
Avci FY;Li X;Tsuji M;Kasper DL
通讯作者:
Kasper DL