Biology subjects

Haraldsson, G.

Publications and source records attributed to Haraldsson, G..

4 recordsLinked to original sources

bioRxiv2025

Intra-host genomic variation of Haemophilus influenzae isolates from asymptomatic nasopharyngeal carriers involves genes encoding proteins with diverse inferred functions

Haemophilus influenzae is a human-specific pathogen that causes infections ranging in severity from otitis media to potentially fatal meningitis. It also asymptomatically colonizes the upper respiratory tract. Although intra-host genomic variation of H. influenzae has been investigated in some anatomic sites, the genes most frequently acquiring nonsynonymous (amino acid changing) or nonsense (protein truncating) single nucleotide polymorphisms (SNPs) during human carriage or infection remain largely unidentified. To study intra-host genomic variation of H. influenzae during human asymptomatic carriage in the nasopharynx, the genomes of 805 isolates recovered from 24 healthy Icelandic children were sequenced. Most children were colonized with isolates with a single multilocus sequence type (MLST), although some were concurrently colonized with isolates with multiple MLSTs. Intra-host genomic variation was discovered with 120 genes acquiring SNPs in at least one isolate. Among them, 69 genes were recurrently polymorphic in isolates recovered from multiple children, and 72 SNPs occurred in multiple isolates recovered from the same child. The polymorphic genes encode proteins with diverse inferred functions, including transcription regulators and putative virulence factors. Many of the proteins likely play roles in bacterial fitness, virulence, and host-pathogen molecular interactions. This intra-host variation study provides a model for understanding the genomic diversity acquired by H. influenzae during human asymptomatic carriage in the nasopharynx.

microbiology↗

bioRxiv2022

Nasopharyngeal competition dynamics are likely to be altered following vaccine introduction: bacteriocin prevalence and diversity among Icelandic and Kenyan pneumococci

Bacteriocins are antimicrobial peptides produced by bacteria to inhibit other bacteria in the surrounding environment. Streptococcus pneumoniae is a leading cause of disease worldwide and colonises the healthy human nasopharynx, where it competes for space and nutrients. Pneumococcal conjugate vaccines have reduced the incidence of disease, but they also restructure the bacterial population, and this restructuring likely alters the nasopharyngeal competition dynamics. Here, the distribution of bacteriocins was examined in over 5000 carriage and disease-causing pneumococci from Iceland and Kenya, recovered before and after the introduction of pneumococcal vaccination. Overall, up to eleven different bacteriocin gene clusters were identified per pneumococcus. Significant differences in the prevalence of bacteriocins were observed before and after vaccine introduction, and among carriage and disease-causing pneumococci, which were largely explained by the bacterial population structure. Genetically similar pneumococci generally harboured the same bacteriocins although sometimes different repertoires of bacteriocins were observed, which suggested that horizontal transfer of bacteriocin clusters had occurred. These findings demonstrated that vaccine-mediated changes in the pneumococcal population altered the prevalence and distribution of bacteriocins. The consequences of this for pneumococcal colonisation and disease remain to be determined.

genomics↗

bioRxiv2020

Population genomic molecular epidemiological study of macrolide resistant Streptococcus pyogenes in Iceland,1995-2016: Identification of a large clonal population with a pbp2x mutation conferring reduced in vitro beta-lactam susceptibility

Resistance to macrolide antibiotics is a global concern in the treatment of Streptococcus pyogenes (Group A Streptococcus, GAS) infections. In Iceland, since the detection of the first macrolide-resistant isolate in 1998, three epidemic waves of macrolide-resistant GAS infections have occurred with peaks in 1999, 2004, and 2008. We conducted whole genome sequencing of all 1,575 available GAS macrolide-resistant clinical isolates of all infection types collected at the national reference laboratory in Reykjavik from 1998 to 2016. Among 1,515 erythromycin-resistant isolates, 90.3% were of only three emm types: emm4 (n = 713), emm6 (n = 324), and emm12 (n = 332), with each being predominant in a distinct epidemic peak. The antibiotic efflux pump genes, mef(A) and msr(D), were present on chimeric mobile genetic elements in 99.3% of the macrolide-resistant isolates of these emm types. Of note, in addition to macrolide resistance, virtually all emm12 isolates had a single amino acid substitution in penicillin-binding protein PBP2X that conferred a two-fold increased penicillin G and ampicillin MIC among isolates tested. We conclude that each of the three large epidemic peaks of macrolide-resistant GAS infections occurring in Iceland since 1998 was caused by the emergence and clonal expansion of progenitor strains, with macrolide resistance being conferred predominantly by inducible Mef(A)-Msr(D) drug efflux pumps. The occurrence of emm12 strains with macrolide resistance and decreased beta-lactam susceptibility was unexpected and is of public health concern. RepositoriesGenomic sequencing data for all 1,515 macrolide/erythromycin-resistant isolates were deposited into the National Center for Biotechnology Information Sequence Read Archive under bioproject accession PRJNA614628 and assembled sequences for composite elements {Phi}29854, {Phi}29862 and {Phi}29661 were deposited in Genbank under accessions ###, ### and ### respectively.

genomics↗

bioRxiv2017

Heterogeneity Among Estimates Of The Core Genome And Pan-Genome In Different Pneumococcal Populations

BackgroundUnderstanding the structure of a bacterial population is essential in order to understand bacterial evolution, or which genetic lineages cause disease, or the consequences of perturbations to the bacterial population. Estimating the core genome, the genes common to all or nearly all strains of a species, is an essential component of such analyses. The size and composition of the core genome varies by dataset, but our hypothesis was that variation between different collections of the same bacterial species should be minimal. To test this, the genome sequences of 3,121 pneumococci recovered from healthy individuals in Reykjavik (Iceland), Southampton (United Kingdom), Boston (USA) and Maela (Thailand) were analysed.\n\nResultsThe analyses revealed a supercore genome (genes shared by all 3,121 pneumococci) of only 303 genes, although 461 additional core genes were shared by pneumococci from Reykjavik, Southampton and Boston. Overall, the size and composition of the core genomes and pan-genomes among pneumococci recovered in Reykjavik, Southampton and Boston were very similar, but pneumococci from Maela were distinctly different. Inspection of the pan-genome of Maela pneumococci revealed several >25 Kb sequence regions that were homologous to genomic regions found in other bacterial species.\n\nConclusionsSome subsets of the global pneumococcal population are highly heterogeneous and thus our hypothesis was rejected. This is an essential point of consideration before generalising the findings from a single dataset to the wider pneumococcal population.

genomics↗