Biology subjects

Oggioni, M. R.

Publications and source records attributed to Oggioni, M. R..

7 recordsLinked to original sources

bioRxiv2026

Genomic variation and ancestry of Helicobacter pylori in the admixed population of Cabo Verde reveal host adaptation, limited host-pathogen ancestry concordance, and signatures of trans-Atlantic slave trade migrations

The genomic structure of the stomach-colonising, gastric cancer-associated bacterium Helicobacter pylori mirrors human evolutionary history, making it difficult to disentangle shared ancestry from true host-pathogen interactions driving disease risk. Recently admixed populations offer opportunities for new coevolutionary trajectories between H. pylori and its host that may disrupt parallel evolution. Here, we analyse host H. pylori IgG, blood serum biomarkers, and paired host-bacterial genomic data from the general population (independent of dyspepsia symptoms) of Cabo Verde. Seropositivity is high (82.8%), as in neighbouring African populations. Serum biomarkers indicate that this unique cohort mainly comprises hosts with limited gastric inflammation. Genomic analyses show that Cabo Verdean H. pylori derive European (hspSWeurope) and West African (hspAfrica1WAfrica) ancestry. The delineation of a reference dataset that includes new strains from Ghana and Portugal, uncovered a distinct West-Central African cluster (hspAfrica1WCAfrica). This dataset allowed inference of within-Africa and within-Europe ancestries in Cabo Verdean and American strains that reflect historical migrations linked to European colonisation and the trans-Atlantic Slave Trade. European strains in Cabo Verde show additional population structure, including two low-diversity clusters. Approximate Bayesian Computation (ABC) inference indicates that the most common cluster represents a clonal expansion, likely driven by host adaptation leading to increased transmission within Cabo Verde. Notably, these strains lack known virulence genes and show significant divergence from gastric cancer strains. Finally, host and bacterial ancestry are uncoupled, indicating disruption of ancestral parallel evolution. Cabo Verde, therefore, provides a unique natural model for studying host-pathogen interactions underlying susceptibility to H. pylori.

evolutionary biology↗

bioRxiv2025

Simple Sequence Repeats Mediate Phase Variation of the Mucoid Phenotype in Hypervirulent Klebsiella pneumoniae

Hypervirulent Klebsiella pneumoniae (HVKp) express a thick mucoid capsular polysaccharide which is essential for virulence and survival in the bloodstream but inhibits epithelial adhesion and invasion. The molecular mechanisms regulating capsule expression to rapidly adapt to these distinct niches are unknown. Here, we show that high frequency mutations in a poly-G repeat in the regulator of mucoid phenotype gene, rmpA, mediates reversible ON/OFF phase variation of the mucoid phenotype. We find that these mutations generate subpopulations of bacteria with reduced capsule expression and mucoidy. In vitro and in vivo infection models reveal that phase variation to the OFF state facilitates epithelial cell infection while ON switching enhances resistance to the bactericidal activity of human serum and systemic spread to the liver and spleen in a murine infection model. Genomic analysis reveals that the phase variation mechanism is a conserved feature of all HVKp and that additional novel DNA repeats in rmpD and rmpC drive different combinations of capsule mucoidy and hyperexpression phenotypes. These findings establish a mechanistic basis for how HVKp occupy such a diverse array of niches during infection, with important implications for the design and implementation of Kp-specific vaccines and therapies.

microbiology↗

bioRxiv2023

Long-term evolution of Streptococcus mitis and Streptococcus pneumoniae leads to higher genetic diversity within rather than between human populations

Evaluation of the apportionment of genetic diversity of bacterial commensals within and between populations is an important step in the characterization of their evolutionary potential. Recent studies showed a correlation between the genomic diversity of human commensal strains and that of their host, but the strength of this correlation and of the geographic structure among populations is a matter of debate. Here, we studied the genomic diversity and evolution of the phylogenetically related oronasopharingeal healthy-carriage Streptococcus mitis and Streptococcus pneumoniae, whose lifestyles range from stricter commensalism to high pathogenic potential. A total of 119 S. mitis genomes showed higher within- and among-host variation than 810 S. pneumoniae genomes in European, East Asian and African populations. Summary statistics of the site-frequency spectrum for synonymous and non-synonymous variation and ABC modelling showed this difference to be due to higher historical population effective size (Ne) in S. mitis, whose genomic variation been maintained close to mutation-drift equilibrium across (at least many) generations, whereas S. pneumoniae has been expanding from a smaller ancestral population and has been subjected to adaptive selection. Strikingly, both species show limited differentiation among populations. As genetic differentiation is inversely proportional to the product of effective population size and migration rate (Nem), we argue that large Ne have led to similar differentiation patterns, even if m is very low for S. mitis. We conclude that more diversity within than among human populations and limited population differentiation must be common features of the human microbiome due to large Ne.

evolutionary biology↗

bioRxiv2022

Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 100 immunologically-distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally-disseminated strain, GPSC12 (CC180), which was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage {phi}OXC141. Prior to the introduction of PCV13, this clades composition shifted towards a {phi}OXC141-negative subpopulation in a systematically-sampled UK collection. In the post-PCV era, more rapidly-recombining non-Clade I isolates, also {phi}OXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the [~]100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage {phi}OXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in [~]30% of all pneumococci, and was particularly common in the unusually-clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR data demonstrated the altered csRNA3 was more effective at inhibiting production of the competence stimulating peptide pheromone. This interference with the quorum sensing needed to induce competence lowered the rate of spontaneous transformation, reducing the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics.

microbiology↗

bioRxiv2022

Moonlighting proteins activate transformation in multidrug-resistant Streptococcus pneumoniae epigenetic phase variants

Despite enabling Streptococcus pneumoniae to acquire antibiotic resistance and evade vaccine-induced immunity, transformation occurs at variable rates across pneumococci. Phase variants of isolate RMV7, distinguished by altered methylation patterns driven by the translocating variable restriction-modification (tvr) locus, differed significantly in their transformation efficiencies and biofilm thicknesses. These differences were replicated when the corresponding tvr alleles were introduced into an RMV7 derivative lacking the locus. RNA-seq identified differential expression of the type 1 pilus, causing the variation in biofilm formation, and inhibition of competence induction in the less transformable variant, RMV7domi. This was partly attributable to lower expression of ManLMN in RMV7domi, which promoted competence induction through importing N-acetylglucosamine. This effect was potentiated by orthologues of the gram-negative competence regulatory machinery. Furthermore, a phage-related chromosomal island was more active in RMV7domi, which inhibited transformation by increasing expression of the stress response proteins ClpP and HrcA. However, HrcA increased competence induction in the other variant, with its effects depending on Ca2+ supplementation or heat shock. Hence the heterogeneity in transformation efficiency likely reflects the diverse signalling pathways by which it is affected. This regulatory complexity will modulate population-wide responses to synchronising quorum sensing signals to produce co-ordinated yet stochastic "bet hedging" behaviour.

microbiology↗

bioRxiv2022

Diurnal differences in intracellular replication within splenic macrophages correlates with the outcome of pneumococcal infection.

Circadian rhythms affect the progression and severity of bacterial infections including those caused by Streptococcus pneumoniae, but the mechanisms responsible for this phenomenon remain largely elusive. Following advances in our understanding of the role of replication of S. pneumoniae within a specific subset of splenic macrophages, we sought to investigate events within the spleen that correlate with differential outcomes of invasive pneumococcal infection. Utilising murine invasive pneumococcal disease (IPD) models, here we report that infection during the murine active phase (zeitgeber time; 15h after start of light cycle, 3h after start of dark cycle) resulted in significantly faster onset of moderate septicaemia compared to rest phase (zeitgeber time 3; 3h after start of light cycle) infection. These findings correlated with significantly higher pneumococcal burden within the spleen of active phase-infected mice at early time points compared to rest phase-infected mice. Whole-section confocal microscopy analysis of these spleens revealed that the number of pneumococci is significantly higher exclusively within marginal zone metallophilic macrophages (MMMs), known to allow intracellular pneumococcal replication as a prerequisite step to the onset of septicaemia. Pneumococcal clusters within MMMs were more abundant and increased in size in active phase-infected mice compared to those in rest phase-infected mice which decreased in size over time and were present in a lower percentage of MMMs. This phenomenon preceded significantly higher levels of bacteraemia alongside serum IL-6 and TNF- concentrations in active phase-infected mice following re-seeding of pneumococci into the blood. In summary, these data link the difference in susceptibility to invasive pneumococcal infection to variation in the ability of MMMs to successfully control and digest phagocytosed bacteria. Author summaryCircadian rhythms are present within the majority of multicellular organisms and influence almost all aspects of our physiology. As such, circadian rhythm disorders have been shown to result in an increased susceptibility to certain diseases. The effects of host circadian rhythm have been also mirrored in rodent studies, with the outcome of Streptococcus pneumoniae infection being dependent on the time of challenge. Whilst studies into the functional effects of circadian rhythm on the host immune system are present, knowledge of how these contribute to the control of invasive S. pneumoniae infection are lacking, especially considering the recent breakthrough in understanding the stages of pneumococcal pathogenesis. We show here that mice infected with S. pneumoniae during their active phase developed septicaemia quicker than those infected during their rest phase. We demonstrate that this is likely due to increased replication of pneumococci specifically within a subset of splenic macrophages, which subsequently results in increased numbers of pneumococci in the blood and higher levels of pro-inflammatory cytokines which result in septicaemia. These data provide novel insights into how circadian rhythm influences the immune functionality of the spleen, and how the regulation of function of one macrophage subtype can significantly alter the course of infection.

microbiology↗

bioRxiv2020

A virulence associated siderophore importer causes antimicrobial efflux in Klebsiella pneumoniae

The accessory genome of many pathogenic bacteria includes ABC transporters that scavenge metal by siderophore uptake and ABC transporters that contribute to antimicrobial resistance by multidrug efflux. There are mechanistic and recently recognised structural similarities between siderophore importer proteins and efflux pumps. Here we investigated the influence of siderophore importer YbtPQ on antimicrobial resistance of Klebsiella pneumoniae. YbtPQ is encoded in the yersiniabactin cluster in a prevalent mobile genetic element ICEKp, and is also common in pathogenicity islands of Escherichia coli and Yersinia species, where yersiniabactin enhances virulence. Deletion of ICEKp increased the sensitivity of K. pneumoniae to all antimicrobials tested. The mechanism was dependent on the yersiniabactin importer YbtPQ and involved antimicrobial efflux, since it was affected by the inhibitor reserpine. The element ICEKp is naturally highly mobile, indeed the accessory genome of K. pneumoniae is recognised as a reservoir of genes for the emergence of hospital outbreak strains and for transfer to other Gram-negative pathogens. Introduction of ICEKp, or a plasmid encoding YbtPQ, to E. coli decreased its sensitivity to a broad range of antimicrobials. Thus, a confirmed siderophore importer, on a rapidly evolving and highly mobile element capable of interspecies transfer, may have a secondary function exporting antimicrobials.

microbiology↗