Immunization with proline rich region of pneumococcal surface protein A has no role in protection against Streptococcus pneumoniae serotype 19F

Girgis, Michael M.; El‐Aziz, Abeer M. Abd; Hassan, Ramadan; Ali, Youssif M.

doi:10.1016/j.micpath.2019.103761

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…Proline-Rich Domains have a modular structure and connect the N-terminal region with the cell wall anchor. The proposed role as a bacterial cell wall-spanning domain is consistent with the position prior to the anchor (49, 50). Our in silico analysis identified a modular composition and further distinct proline-rich domains, which differ in length (57 to 286 aa), type, module composition, and sequence.…”

Section: Resultssupporting

confidence: 63%

Same, Same, but Different: Molecular Analyses ofStreptococcus pneumoniaeImmune Evasion Proteins Identifies new Domains and Reveals Structural Differences between PspC and Hic Variants

Vilhena

King

et al. 2020

Preprint

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PspC and Hic proteins of Streptococcus pneumoniae are some of the most variable microbial immune evasion proteins identified to date. Due to structural similarities and conserved binding profiles it was assumed over a long time that these pneumococcal surface proteins represent a protein family, comprising eleven subgroups. Recently, however, by evaluating more proteins larger diversity of individual proteins became apparent. In contrast to previous assumptions a pattern evaluation of six PspC and five Hic variants, each representing one of the previously defined subgroups, revealed distinct structural and likely functionally regions of the proteins, and identified nine new domains and new domain alternates. Several domains are unique to PspC and Hic variants, while other domains are shared with other S. pneumoniae and bacterial virulent determinants. This understanding improved pattern evaluation on the level of full-length proteins, allowed a sequence comparison on the domain level and furthermore identified domains with a modular composition. This novel concept allows a better characterization of variability, and modular domain composition of individual proteins, enables a structural and functional characterization at the domain level and furthermore shows substantial structural differences between PspC and Hic proteins. Such knowledge will also be useful for molecular strain typing, characterizing PspC and Hic proteins from new clinical S. pneumoniae strains, including those derived from patients who present with pneumococcal hemolytic uremic syndrome. Furthermore this analysis explains the role of multifaceted intact PspC and Hic proteins in pathogen host interactions. and can provide a basis for rational vaccine design.

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Section: Resultssupporting

confidence: 63%

Same, Same, but Different: Molecular Analyses ofStreptococcus pneumoniaeImmune Evasion Proteins Identifies new Domains and Reveals Structural Differences between PspC and Hic Variants

Vilhena

King

et al. 2020

Preprint

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show abstract

“…Proline-Rich Domains have a modular structure and connect the N-terminal region to the cell wall anchor 51 . The proposed role of these domains as spanning the bacterial cell wall-spanning is consistent with the position proximal to the anchor 51 , 52 . Our in-silico analysis identified a modular composition and further distinct proline-rich domains, which differ in length (57 to 286 aa), modular composition, and sequence.…”

Section: Resultsmentioning

confidence: 99%

Molecular analyses identifies new domains and structural differences among Streptococcus pneumoniae immune evasion proteins PspC and Hic

Vilhena

King

et al. 2021

Sci Rep

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The PspC and Hic proteins of Streptococcuspneumoniae are some of the most variable microbial immune evasion proteins identified to date. Due to structural similarities and conserved binding profiles, it was assumed for a long time that these pneumococcal surface proteins represent a protein family comprised of eleven subgroups. Recently, however, the evaluation of more proteins revealed a greater diversity of individual proteins. In contrast to previous assumptions a pattern evaluation of six PspC and five Hic variants, each representing one of the previously defined subgroups, revealed distinct structural and likely functionally regions of the proteins, and identified nine new domains and new domain alternates. Several domains are unique to PspC and Hic variants, while other domains are also present in other virulence factors encoded by pneumococci and other bacterial pathogens. This knowledge improved pattern evaluation at the level of full-length proteins, allowed a sequence comparison at the domain level and identified domains with a modular composition. This novel strategy increased understanding of individual proteins variability and modular domain composition, enabled a structural and functional characterization at the domain level and furthermore revealed substantial structural differences between PspC and Hic proteins. Given the exceptional genomic diversity of the multifunctional PspC and Hic proteins a detailed structural and functional evaluation need to be performed at the strain level. Such knowledge will also be useful for molecular strain typing and characterizing PspC and Hic proteins from new clinical S. pneumoniae strains.

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“…Purified recombinant proteins were used to immunize female BALB/c mice (20–25 gm weight) as described previously with minor modifications (Girgis et al 2020 ). In brief, each mouse was injected subcutaneously (SC) with a mixture of 300 µg protein and 2 mg aluminum hydroxide [Alum (Sigma-Aldrich Co., USA)] as adjuvant, in 200 µl saline.…”

Section: Methodsmentioning

confidence: 99%

A novel pentavalent vaccine candidate completely protects against Acinetobacter baumannii in a mouse model of peritonitis

Hagag

Said

Kenawy

et al. 2022

Appl Microbiol Biotechnol

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Acinetobacter baumannii is considered as one of the most virulent and infectious organisms that have an increased ability to both evade host immune response and resist various classes of antibiotics, leading to life-threatening infections. Multiple virulence factors have been implicated in the high prevalence rate of A. baumannii in hospitalized and immunocompromised patients. Moreover, improper use of antibiotics has led to the emergence of extensive drug-resistant strains that urgently require alternative strategies to control this superbug. Unfortunately, the availability of a licensed vaccine against A. baumannii infections is still challenged by the vast diversity among A. baumannii strains. Here, we report the development of a novel pentavalent vaccine candidate composed of two recombinant proteins (Wza and YiaD) and a pool of capsular polysaccharides isolated from 3 clinical isolates. We tested this new vaccine in vivo in a mouse model of peritonitis against the standard strain ATCC 19606 in addition to 3 clinical isolates of A. baumannii. Immunization with this vaccine completely protected the challenged mice with 100% survival rate in the case of all the tested bacteria. Further clinical studies are urgently needed to evaluate the efficacy and safety of this proprietary vaccine to protect patients from A. baumannii lethal infections. Key points • Recombinant proteins pool (Wza and YiaD) immunization led to a synergistic immune response. • Capsular polysaccharides pool induced up to 90% protection of tested clinical isolates. • The pentavalent pool showed superiority with 100% survival of immunized mice.

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Immunization with proline rich region of pneumococcal surface protein A has no role in protection against Streptococcus pneumoniae serotype 19F

Cited by 5 publications

References 30 publications

Same, Same, but Different: Molecular Analyses ofStreptococcus pneumoniaeImmune Evasion Proteins Identifies new Domains and Reveals Structural Differences between PspC and Hic Variants

Same, Same, but Different: Molecular Analyses ofStreptococcus pneumoniaeImmune Evasion Proteins Identifies new Domains and Reveals Structural Differences between PspC and Hic Variants

Molecular analyses identifies new domains and structural differences among Streptococcus pneumoniae immune evasion proteins PspC and Hic

A novel pentavalent vaccine candidate completely protects against Acinetobacter baumannii in a mouse model of peritonitis

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