Browsing by Author "Langereis, Jeroen D."
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- Antibody Binding and Complement-Mediated Killing of Invasive Haemophilus influenzae Isolates from Spain, Portugal, and the NetherlandsPublication . Dudukina, Elena; de Smit, Laura; Verhagen, Giel J.A.; van de Ende, Arie; Marimón, José María; Bajanca-Lavado, Paula; Ardanuy, Carmen; Marti, Sara; de Jonge, Marien I.; Langereis, Jeroen D.Haemophilus influenzae is a Gram-negative bacterium that can be classified into typeable (types a through f) and nontypeable (NTHi) groups. This opportunistic pathogen asymptomatically colonizes the mucosal epithelium of the upper respiratory tract, from where it spreads to other neighboring regions, potentially leading to disease. Infection with NTHi can cause otitis media, sinusitis, conjunctivitis, exacerbations of chronic obstructive pulmonary disease, and pneumonia, but it is increasingly causing invasive disease, including bacteremia and meningitis. Invasive NTHi strains are more resistant to complement-mediated killing. However, the mechanisms of complement resistance have never been studied in large numbers of invasive NTHi strains. In this study, we determined the relationship between binding of IgG or IgM and the bacterial survival in normal human serum for 267 invasive H. influenzae strains from Spain, Portugal, and the Netherlands, of which the majority (200 [75%]) were NTHi. NTHi bacteria opsonized with high levels of IgM had the lowest survival in human serum. IgM binding to the bacterial surface, but not IgG binding, was shown to be associated with complement-mediated killing of NTHi strains. We conclude that evasion of IgM binding by NTHi strains increases survival in blood, thereby potentially contributing to their ability to cause severe invasive diseases.
- Comparative pangenome analysis of capsulated Haemophilus influenzae serotype f highlights their high genomic stabilityPublication . Gonzalez-Diaz, Aida; Carrera-Salinas, Anna; Pinto, Miguel; Cubero, Meritxell; van der Ende, Arie; Langereis, Jeroen D.; Domínguez, M. Ángeles; Ardanuy, Carmen; Bajanca-Lavado, Paula; Marti, SaraHaemophilus influenzae is an opportunistic pathogen adapted to the human respiratory tract. Non-typeable H. influenzae are highly heterogeneous, but few studies have analysed the genomic variability of capsulated strains. This study aims to examine the genetic diversity of 37 serotype f isolates from the Netherlands, Portugal, and Spain, and to compare all capsulated genomes available on public databases. Serotype f isolates belonged to CC124 and shared few single nucleotide polymorphisms (SNPs) (n = 10,999), but a high core genome (> 80%). Three main clades were identified by the presence of 75, 60 and 41 exclusive genes for each clade, respectively. Multi-locus sequence type analysis of all capsulated genomes revealed a reduced number of clonal complexes associated with each serotype. Pangenome analysis showed a large pool of genes (n = 6360), many of which were accessory genome (n = 5323). Phylogenetic analysis revealed that serotypes a, b, and f had greater diversity. The total number of SNPs in serotype f was significantly lower than in serotypes a, b, and e (p < 0.0001), indicating low variability within the serotype f clonal complexes. Capsulated H. influenzae are genetically homogeneous, with few lineages in each serotype. Serotype f has high genetic stability regardless of time and country of isolation.
- Epidemiological analysis of invasive Haemophilus influenzae clinical isolates obtanied from Portugal, Spain and the NetherlandsPublication . Raeven, Elisabeth A.M.; González, Aida; van der Ende, Arie; Liñares, Josefina; Marimón, José María; Bajanca-Lavado, Paula; Langereis, Jeroen D.; Ardanuy, Carmen; Martí, SaraBackground. Haemophilus influenzae is a human-restricted pathogen that forms part of the normal nasopharyngeal microbiota. The introduction of the H. influenzae serotype b vaccine has drastically decreased the number of bacteremia cases caused by H. influenzae serotype b (Hib). Conversely, the cases of non-typeable H. influenzae (NTHi) bacteremia have increased substantially. Therefore, we aimed to perform an epidemiological study comparing invasive H. influenzae clinical isolates from three European countries. Material & Methods. Clinical isolates were obtained from two southern European countries, Spain (Hospital de Bellvitge, n=44; Hospital de Donostia, n=18) and Portugal (n=55), and a northern country, the Netherlands (n=146) between 2013 and 2015. The clinical source of the samples was blood (n=250), cerebrospinal fluid (n=4) and pleural effusion (n=9). Capsular serotyping was done by PCR and genotyping by PFGE (SmaI), followed by FingerPrinting analysis. Antimicrobial susceptibility was tested by disk diffusion and microdilution against Ampicillin (AP), Tetracycline (TC), Chloramphenicol (CL), Ciprofloxacin (CP) and Trimethoprim/Sulfamethoxazole (T/S). Results. Overall, NTHi were the most prevalent isolates (201/263, 76%), followed by Hib (38/263, 14%), Hif (16/263, 6%) and other capsulated H. influenzae (Hia=3; Hid=1; Hie=4). By countries, NTHi was also the major pathogen identified in Spain (82%), Portugal (80%) and the Netherlands (73%), while Hib was slightly more frequent in the Netherlands (27/146, 18%) and Portugal (7/55, 13%) than in Spain (4/62, 6%). PFGE clustering identified high diversity among the NTHi strains, although some strains from different countries were found to be highly related (14 clusters of two or three strains). Hib were grouped together in four main clusters including isolates from different countries: Cluster I (5 strains Netherlands; 4 strains Portugal), Cluster II (18 strains Netherlands, 2 strains Portugal; 1 strain Spain), Cluster III (5 strains Netherlands), Cluster IV (1 strain Portugal; 1 strain Spain).
- Spatial and temporal genomic homogeneity among Haemophilus influenzae serotype fPublication . Gonzalez-Diaz, Aida; Pinto, Miguel; Cubero, Meritxell; Langereis, Jeroen D.; van der Ende, Arie; Bajanca-Lavado, Maria Paula; Ardanuy, Carmen; Marti, SaraBackground: Haemophilus influenzae is an opportunistic pathogen highly adapted to the human respiratory tract which is often reported as the etiologic agent of infectious diseases. After the introduction of serotype b vaccine, non-typeable H. influenzae (NTHi) has become the most frequent cause of respiratory infection, followed in frequency by serotype f strains (Hif). The aim of this study was to analyze the genomic diversity among invasive and colonizing Hif isolates by whole genome sequencing (WGS).