Immunization with the iron uptake ABC transporter proteins PiaA and PiuA prevents respiratory infection with Streptococcus pneumoniae

Jomaa, Maha; Terry, Stephen J.; Hale, Chris; Jones, Christopher; Dougan, Gordon; Brown, Jeremy S.

doi:10.1016/j.vaccine.2006.04.012

Cited by 39 publications

(21 citation statements)

References 28 publications

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“…A co-immunization study of S. pneumoniae , PiuA and PiaA, showed using the two iron SBPs antigens produced additive protection in mice [131]. Mechanistic studies explained how anti-PiaA and anti-PiuA polyclonal rabbit antibodies did not inhibit growth of S. pneumoniae in iron-restricted conditions, indicating these antibodies protect mice against S. pneumoniae infection by promoting opsonophagocytosis, not restricting iron transport by the SBPs [132]. Immunization with recombinant manganese SBP, MntC, elicits an anti-MntC IgG response capable of protecting mice against S. aureus [133].…”

Section: Discussionmentioning

confidence: 99%

Selective substrate uptake: The role of ATP-binding cassette (ABC) importers in pathogenesis

Tanaka

Song

Mason

et al. 2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

129

102

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The uptake of nutrients, including metals, amino acids and peptides are required for many biological processes. Pathogenic bacteria scavenge these essential nutrients from microenvironments to survive within the host. Pathogens must utilize a myriad of mechanisms to acquire these essential nutrients from the host while mediating the effects of toxicity. Bacteria utilize several transport proteins, including ATP-binding cassette (ABC) transporters to import and expel substrates. ABC transporters, conserved across all organisms, are powered by the energy from ATP to move substrates across cellular membranes. In this review, we will focus on nutrient uptake, the role of ABC importers at the host-pathogen interface, and explore emerging therapies to combat pathogenesis. This article is part of a Special Issue entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by Ute Hellmich, Rupak Doshi and Benjamin McIlwain.

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Section: Discussionmentioning

confidence: 99%

Selective substrate uptake: The role of ATP-binding cassette (ABC) importers in pathogenesis

Tanaka

Song

Mason

et al. 2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

129

102

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“…S. pneumoniae strains used for this study were M87 (ST4) and Io11697 (ST23F), both gifts from Brian Spratt, Imperial College London (25), and D39 (ST2). Bacteria were cultured at 37°C in 5% CO 2 on blood agar plates or in Todd-Hewitt broth supplemented with 0.5% yeast extract to an optical density at 580 nm of 0.4 (approximately 10 8 CFU/ml) and stored at Ϫ70°C in 10% glycerol as single-use aliquots.…”

Section: Methodsmentioning

confidence: 99%

Impaired Opsonization with C3b and Phagocytosis ofStreptococcus pneumoniaein Sera from Subjects with Defects in the Classical Complement Pathway

et al. 2008

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Results from studies using mice deficient in specific complement factors and clinical data on patients with an inherited deficiency of the classical complement pathway component C2 suggest that the classical pathway is vital for immunity to Streptococcus pneumoniae. However, the consequences of defects in classical pathway activity for opsonization with C3b and the phagocytosis of different S. pneumoniae serotypes in human serum are not known, and there has not been a systematic analysis of the abilities of sera from subjects with a C2 deficiency to opsonize S. pneumoniae. Hence, to investigate the role of the classical pathway in immunity to S. pneumoniae in more detail, flow cytometry assays of opsonization with C3b and the phagocytosis of three capsular serotypes of S. pneumoniae were performed using human sera depleted of the complement factor C1q or B or sera obtained from C2-deficient subjects. The results demonstrate that, in human serum, the classical pathway is vital for C3b-iC3b deposition onto cells of all three serotypes of S. pneumoniae and seems to be more important than the alternative pathway for phagocytosis. Compared to the results for sera from normal subjects, C3b-iC3b deposition and total anti-S. pneumoniae antibody activity levels in sera obtained from C2 ؊/؊ subjects were reduced and the efficiency of phagocytosis of all three S. pneumoniae strains was impaired. Anticapsular antibody levels did not correlate with phagocytosis or C3b-iC3b deposition. These data confirm that the classical pathway is vital for complement-mediated phagocytosis of S. pneumoniae and demonstrate why subjects with a C2 deficiency have a marked increase in susceptibility to S. pneumoniae infections.

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“…This strategy has been used against many pathogens: in fact, iron import systems have previously been the target of a vaccine for Staphylococcus aureus (Ebert et al, 2010; Kim et al, 2010; Joshi et al, 2012; Pancari et al, 2012; Zapotoczna et al, 2013). Therefore, studies established by Brown et al and expanded upon by Jomaa et al used two of the iron import systems, Piu and Pia, as possible vaccine candidates (Brown et al, 2001b; Jomaa et al, 2005, 2006). Because PiuA and PiaA proteins are found in all pneumococcal serotypes tested, each protein was used (individually and together) to immunize mice for antibody responses and protection from subsequent pneumococcal challenge (Brown et al, 2001b).…”

Section: Ironmentioning

confidence: 99%

“…As expected, immunization with both antigens further reduced the mortality rate. Passive immunization with antisera against PiaA-PiuA also significantly delayed time-to-death, indicating that immunization is at least partially antibody-mediated (Jomaa et al, 2005, 2006). Together, these data demonstrate that the lipoprotein components of two iron import systems can be used as a protein-based vaccine to protect against systemic pneumococcal infection.…”

Section: Ironmentioning

confidence: 99%

The roles of transition metals in the physiology and pathogenesis of Streptococcus pneumoniae

Honsa

Johnson

Rosch

2013

Front. Cell. Infect. Microbiol.

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For bacterial pathogens whose sole environmental reservoir is the human host, the acquisition of essential nutrients, particularly transition metals, is a critical aspect of survival due to tight sequestration and limitation strategies deployed to curtail pathogen outgrowth. As such, these bacteria have developed diverse, specialized acquisition mechanisms to obtain these metals from the niches of the body in which they reside. To oppose the spread of infection, the human host has evolved multiple mechanisms to counter bacterial invasion, including sequestering essential metals away from bacteria and exposing bacteria to lethal concentrations of metals. Hence, to maintain homeostasis within the host, pathogens must be able to acquire necessary metals from host proteins and to export such metals when concentrations become detrimental. Furthermore, this acquisition and efflux equilibrium must occur in a tissue-specific manner because the concentration of metals varies greatly within the various microenvironments of the human body. In this review, we examine the functional roles of the metal import and export systems of the Gram-positive pathogen Streptococcus pneumoniae in both signaling and pathogenesis.

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Immunization with the iron uptake ABC transporter proteins PiaA and PiuA prevents respiratory infection with Streptococcus pneumoniae

Cited by 39 publications

References 28 publications

Selective substrate uptake: The role of ATP-binding cassette (ABC) importers in pathogenesis

Selective substrate uptake: The role of ATP-binding cassette (ABC) importers in pathogenesis

Impaired Opsonization with C3b and Phagocytosis ofStreptococcus pneumoniaein Sera from Subjects with Defects in the Classical Complement Pathway

The roles of transition metals in the physiology and pathogenesis of Streptococcus pneumoniae

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