New article published
Thofte O, Kaur R, Su YC, Brant M, Rudin A, Hood D, Riesbeck K.
Eur J Immunol. 2019 Mar;49(3):490-499. doi: 10.1002/eji.201847871. Epub 2019 Jan 3. PubMed PMID: 30566236
Abstract
The effect of pneumococcal conjugate vaccines (PCV) on invasive pneumococcal disease is frequently reported, but the impact on upper respiratory tract infections in a clinical setting is less documented. Our aim in this 5-year observational study was to investigate serotype changes in a large number of Streptococcus pneumoniae upper respiratory tract isolates following sequential introduction of PCV7 and pneumococcal Haemophilus influenza protein D conjugate vaccine (PHiD-CV10) in a Swedish county.
All bacterial isolates from the upper respiratory tract (nasopharynx, sinus or middle ear fluid) from patients with respiratory tract infections referred to a clinical microbiology laboratory prior to (2 years 2007–2008; n = 1566) and after introduction of PCV (3 years 2011–2013; n = 1707) were prospectively collected. Microbiological findings were compared between the two periods, and information from clinical referrals was recorded in order to explore changes in incidence of pneumococcal acute otitis media (AOM).
Pneumococcal serotypes covered by PHiD-CV10 decreased from 45 to 12 % prior to and after immunization (p < 0.001), respectively. Despite non-PHiD-CV10 serotypes increased from 49 to 80 %, a significant decline of 35 % in the absolute incidence of pneumocococal isolates (p < 0.001) was observed. Finally, the frequency of complicated AOM caused by S. pneumoniae decreased by 32 % (p < 0.001).
After introduction of PCV in 2009, we have observed a significantly decreased number of pneumococcal isolates in the upper respiratory tract, a shift to non-PHiD-CV10 serotypes, and a reduction of complicated AOM. Our findings may have implications for future vaccine design.
Nils Littorin, Jonas Ahl, Fabian Uddén, Fredrik Resman and Kristian Riesbeck
BMC Infect Dis. 2016 Aug 11;16(1):407. doi: 10.1186/s12879-016-1750-5.
Abstract
The effect of pneumococcal conjugate vaccines (PCV) on invasive pneumococcal disease is frequently reported, but the impact on upper respiratory tract infections in a clinical setting is less documented. Our aim in this 5-year observational study was to investigate serotype changes in a large number of Streptococcus pneumoniae upper respiratory tract isolates following sequential introduction of PCV7 and pneumococcal Haemophilus influenza protein D conjugate vaccine (PHiD-CV10) in a Swedish county.
All bacterial isolates from the upper respiratory tract (nasopharynx, sinus or middle ear fluid) from patients with respiratory tract infections referred to a clinical microbiology laboratory prior to (2 years 2007–2008; n = 1566) and after introduction of PCV (3 years 2011–2013; n = 1707) were prospectively collected. Microbiological findings were compared between the two periods, and information from clinical referrals was recorded in order to explore changes in incidence of pneumococcal acute otitis media (AOM).
Pneumococcal serotypes covered by PHiD-CV10 decreased from 45 to 12 % prior to and after immunization (p < 0.001), respectively. Despite non-PHiD-CV10 serotypes increased from 49 to 80 %, a significant decline of 35 % in the absolute incidence of pneumocococal isolates (p < 0.001) was observed. Finally, the frequency of complicated AOM caused by S. pneumoniae decreased by 32 % (p < 0.001).
After introduction of PCV in 2009, we have observed a significantly decreased number of pneumococcal isolates in the upper respiratory tract, a shift to non-PHiD-CV10 serotypes, and a reduction of complicated AOM. Our findings may have implications for future vaccine design.
Conserved Patterns of Microbial Immune Escape: Pathogenic Microbes of Diverse Origin Target the Human Terminal Complement Inhibitor Vitronectin via a Single Common Motif.
Hallström T, Singh B, Kraiczy P, Hammerschmidt S, Skerka C, Zipfel PF, Riesbeck K.
PLoS One. 2016 Jan 25;11(1):e0147709. doi: 10.1371
Abstract
Pathogenicity of many microbes relies on their capacity to resist innate immunity, and to survive and persist in an immunocompetent human host microbes have developed highly efficient and sophisticated complement evasion strategies. Here we show that different human pathogens including Gram-negative and Gram-positive bacteria, as well as the fungal pathogen Candida albicans, acquire the human terminal complement regulator vitronectin to their surface. By using truncated vitronectin fragments we found that all analyzed microbial pathogens (n = 13) bound human vitronectin via the same C-terminal heparin-binding domain (amino acids 352-374). This specific interaction leaves the terminal complement complex (TCC) regulatory region of vitronectin accessible, allowing inhibition of C5b-7 membrane insertion and C9 polymerization. Vitronectin complexed with the various microbes and corresponding proteins was thus functionally active and inhibited complement-mediated C5b-9 deposition. Taken together, diverse microbial pathogens expressing different structurally unrelated vitronectin-binding molecules interact with host vitronectin via the same conserved region to allow versatile control of the host innate immune response.
Identification of type b isolates among Haemophilus influenzae using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Månsson V, Resman F, Kostrzewa M, Nilson B, Riesbeck K.
J Clin Microbiol. 2015 Apr 29. pii: JCM.00137-15.
Abstract
Haemophilus influenzae type b (Hib) is, in contrast to non-b H. influenzae, associated with severe invasive disease such as meningitis and epiglottitis in small children. To date accurate H. influenzae capsule typing requires PCR, a time-consuming and cumbersome method. MALDI-TOF MS provides rapid bacterial diagnostics and is increasingly used in clinical microbiology laboratories. Here MALDI-TOF MS was evaluated as a novel approach to separate Hib from other H. influenzae. PCR-verified Hib and non-Hib reference isolates were selected based on genetic and spectral characteristics. Mass spectra of reference isolates were acquired, and used to generate different classification algorithms for Hib/non-Hib separation using both ClinProTools and MALDI Biotyper software. A test series of mass spectra from 33 Hib and 77 non-Hib isolates, all characterized by PCR, was used to evaluate the algorithms. Several algorithms yielded good results but the two best were a ClinProTools model based on 22 separating peaks and a subtyping main spectra (MSP) model using MALDI Biotyper. The ClinProTools model had a sensitivity of 100%, a specificity of 99% and the results were 98% reproducible using a different MALDI-TOF MS instrument. The Biotyper subtyping MSPs had a sensitivity of 97%, a specificity of 100% and 93% reproducibility. Our results suggest that it is possible to use MALDI-TOF MS to differentiate Hib from other H. influenzae. This is a promising method to rapidly identify Hib in unvaccinated populations, and for screening or surveillance of Hib carriage in vaccinated populations.
Haemophilus influenzae surface fibril (Hsf) is a unique twisted hairpin-like trimeric autotransporter.
Singh B, Jubair TA, Mörgelin M, Sundin A, Linse S, Nilsson UJ, Riesbeck K.
Int J Med Microbiol. 2014 [Epub ahead of print]
Abstract
The Haemophilus surface fibril (Hsf) is an extraordinary large (2413 amino acids) trimeric autotransporter, present in all encapsulated Haemophilus influenzae. It contributes to virulence by directly functioning as an adhesin. Furthermore, Hsf recruits the host factor vitronectin thereby inhibiting the host innate immune response resulting in enhanced survival in serum. Here we observed by electron microscopy that Hsf appears as an 100nm long fibril at the bacterial surface albeit the length is approximately 200nm according to a bioinformatics based model. To unveil this discrepancy, we denaturated Hsf at the surface of Hib by using guanidine hydrochloride (GuHCl). Partial denaturation induced in the presence of GuHCl unfolded the Hsf molecules, and resulted in an increased length of fibres in comparison to the native trimeric form. Importantly, our findings were also verified by E. coli expressing Hsf at its surface. In addition, a set of Hsf-specific peptide antibodies also indicated that the N-terminal of Hsf is located near the C-terminal at the base of the fibril. Taken together, our results demonstrated that Hsf is not a straight molecule but is folded and doubled over. This is the first report that provides the unique structural features of the trimeric autotransporter Hsf.
Haemophilus influenzae stores and distributes hemin by using Protein E.
Al Jubair T, Singh B, Fleury C, Blom AM, Mörgelin M, Thunnissen MM, Riesbeck K. Int J Med Microbiol. 2014 Jul;304(5-6):662-8
Abstract
The human pathogen Haemophilus influenzae causes mainly respiratory tract infections such as acute otitis media in children and exacerbations in patients with chronic obstructive pulmonary disease. We recently revealed the crystal structure of H. influenzeae protein E (PE), a multifunctional adhesin that is involved in direct interactions with lung epithelial cells and host proteins. Based upon the PE structure we here suggest a hypothetical binding pocket that is compatible in size with a hemin molecule. An H. influenzae mutant devoid of PE bound significantly less hemin in comparison to the PE-expressing wild type counterpart. In addition, E. coli expressing PE at the surface resulted in a hemin-binding phenotype. An interaction between hemin and recombinant soluble PE was also demonstrated by native-PAGE and UV-visible spectrophotometry. Surface plasmon resonance revealed an affinity (Kd) of 1.6×10-6M for the hemin-PE interaction. Importantly, hemin that was bound to PE at the H. influenzae surface, was donated to co-cultured luciferase-expressing H. influenzae that were starved of hemin. When hemin is bound to PE it thus may serve as a storage pool for H. influenzae. To our knowledge this is the first report showing that H. influenzae can share hemin via a surface-located outer membrane protein.