Streptococcus pneumoniae Surface Adhesin PfbA Exhibits Host Specificity by Binding to Human Serum Albumin but Not Bovine, Rabbit and Porcine Serum Albumins

Sankar, Sreejanani; Yamaguchi, M.; Kawabata, Shigetada; Ponnuraj, Karthe

doi:10.1007/s10930-019-09875-y

Cited by 9 publications

(5 citation statements)

References 37 publications

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“…In contrast, this figure was 3% of codons for pfbA . We have previously reported that PfbA is pneumococcal cell surface protein that forms a right-handed parallel β-helix and interacts with human fibronectin, plasmin, plasminogen, albumin, hemoglobin, and fibrinogen ( Yamaguchi et al, 2008 ; Beulin et al, 2014 , 2017 ; Radhakrishnan et al, 2018 ; Sankar et al, 2020 ). A BLAST search and phylogenetic analysis showed that pfbA is highly conserved in S. pneumoniae among mitis group Streptococcus ( Yamaguchi et al, 2019b ).…”

Section: Discussionmentioning

confidence: 99%

Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

et al. 2020

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Streptococcus pneumoniae is a major cause of pneumonia, sepsis, and meningitis. Previously, we identified a novel virulence factor by investigating evolutionary selective pressure exerted on pneumococcal choline-binding cell surface proteins. Herein, we focus on another pneumococcal cell surface protein. Cell wall-anchoring proteins containing the LPXTG motif are conserved in Gram-positive bacteria. Our evolutionary analysis showed that among the examined genes, nanA and bgaA had high proportions of codon that were under significant negative selection. Both nanA and bgaA encode a multi-functional glycosidase that aids nutrient acquisition in a glucose-poor environment, pneumococcal adherence to host cells, and evasion from host immunity. However, several studies have shown that the role of BgaA is limited in a mouse pneumonia model, and it remains unclear if BgaA affects pneumococcal pathogenesis in a mouse sepsis model. To evaluate the distribution and pathogenicity of bgaA, we performed phylogenetic analysis and intravenous infection assay. In both Bayesian and maximum likelihood phylogenetic trees, the genetic distances between pneumococcal bgaA was small, and the cluster of pneumococcal bgaA did not contain other bacterial orthologs except for a Streptococcus gwangjuense gene. Evolutionary analysis and BgaA structure indicated BgaA active site was not allowed to change. The mouse infection assay showed that the deletion of bgaA significantly reduced host mortality. These results indicated that both nanA and bgaA encode evolutionally conserved pneumococcal virulence factors and that molecular evolutionary analysis could be a useful alternative strategy for identification of virulence factors.

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Section: Discussionmentioning

confidence: 99%

Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

et al. 2020

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“…BLI has been previously used to study the binding of proteins to HSA. 46 However, due to the multiple fatty acid binding sites on HSA, only qualitative analysis of binding was performed in our study. Biotinylated HSA was captured on streptavidincoated biosensors.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…We examined the hypothesis that our bioconjugates could form a noncovalent bond with albumin through modified fatty acid to extend the half-life in vivo . BLI has been previously used to study the binding of proteins to HSA . However, due to the multiple fatty acid binding sites on HSA, only qualitative analysis of binding was performed in our study.…”

Section: Results and Discussionmentioning

confidence: 99%

Long-Acting Human Interleukin 2 Bioconjugate Modified with Fatty Acids by Sortase A

Qian

Zhang

et al. 2021

Bioconjugate Chem.

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Human Interleukin 2 (IL-2) has already achieved impressive results as a therapeutic agent for cancer and autoimmune diseases. However, one of the limitations associated with the clinical application of IL-2 is its short half-life owing to rapid clearance by the kidneys. Modification with fatty acids, as an albumin noncovalent ligand with the advantage of deep penetration into tissues and high activity-to-mass ratio, is a commonly used approach to improve the half-life of native peptides and proteins. In this investigation, we attempted to extend the half-life of IL-2 through conjugation with a fatty acid using sortase A (srtA). We initially designed and optimized three IL-2 analogues with different peptide linkers between the C-terminus of IL-2 and srtA recognition sequence (LPETG). Among these, analogue A3 was validated as the optimal IL-2 analogue for further modification. Next, six fatty acid moieties with the same fatty acid and different hydrophilic spacers were conjugated to A3 through srtA. The six bioconjugates generated were screened for in vitro biological activity, among which bioconjugate B6 was identified as near-optimal to IL-2. Additionally, B6 could effectively bind albumin through the conjugated fatty acid, which contributed to a significant improvement in its pharmacokinetic properties in vivo. In summary, we have developed a novel IL-2 bioconjugate, B6, modified with fatty acids using srtA, which may effectively serve as a new-generation long-acting IL-2 immunotherapeutic agent.

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“…Furthermore, albumin can increase the viscoelasticity of airway mucus, impeding mucus clearance [197]. Some bacteria, including S. pneumoniae [198] can bind to albumin, exploiting albumin-derived fatty acids as a source of nutrition [199]. Yeast form C. albicans can also aggregate around albumin.…”

Section: Serum Albuminmentioning

confidence: 99%

How Does Airway Surface Liquid Composition Vary in Different Pulmonary Diseases, and How Can We Use This Knowledge to Model Microbial Infections?

Walsh,

Bevan,

Harrison

2024

Microorganisms

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Growth environment greatly alters many facets of pathogen physiology, including pathogenesis and antimicrobial tolerance. The importance of host-mimicking environments for attaining an accurate picture of pathogen behaviour is widely recognised. Whilst this recognition has translated into the extensive development of artificial cystic fibrosis (CF) sputum medium, attempts to mimic the growth environment in other respiratory disease states have been completely neglected. The composition of the airway surface liquid (ASL) in different pulmonary diseases is far less well characterised than CF sputum, making it very difficult for researchers to model these infection environments. In this review, we discuss the components of human ASL, how different lung pathologies affect ASL composition, and how different pathogens interact with these components. This will provide researchers interested in mimicking different respiratory environments with the information necessary to design a host-mimicking medium, allowing for better understanding of how to treat pathogens causing infection in these environments.

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Streptococcus pneumoniae Surface Adhesin PfbA Exhibits Host Specificity by Binding to Human Serum Albumin but Not Bovine, Rabbit and Porcine Serum Albumins

Cited by 9 publications

References 37 publications

Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

Long-Acting Human Interleukin 2 Bioconjugate Modified with Fatty Acids by Sortase A

How Does Airway Surface Liquid Composition Vary in Different Pulmonary Diseases, and How Can We Use This Knowledge to Model Microbial Infections?

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