Biology subjects

Hanski, E.

Publications and source records attributed to Hanski, E..

8 recordsLinked to original sources

bioRxiv2025

Infant gut microbiota in multi-child families converges with adults without a sibling-specific signature

The human gut microbiota undergoes rapid development during early life. Sibling presence has been associated with altered infant microbiota composition and accelerated maturation, but distinguishing direct microbial transmission between siblings from confounding by maternal reproductive history (parity) remains challenging. We analysed >5,000 faecal samples from >800 mother-father-infant triads in the Finnish HELMi birth cohort to characterise microbiota patterns that could inform underlying mechanisms. While sibling presence was associated with accelerated microbiota maturation and modest compositional differences, infants who both had siblings (or both lacked siblings) were no more similar to each other than mixed pairs. Instead, infants with siblings exhibited non-specific convergence with adult microbiota profiles and contributed fewer unique genera to their family metacommunities (infant-mother-father triads). Multi-child families harboured smaller but compositionally distinct metacommunities. These patterns challenge simple models of direct sibling transmission and suggest that multiple factors associated with family structure may jointly influence infant microbiota development, though specific mechanisms remain unclear.

microbiology↗

bioRxiv2025

Age-related changes in the gut microbiota of a long-lived seabird suggest divergence from mammalian models

Gut microbiota plays key roles in shaping host development, immunity, and physiology. The assembly of vertebrate gut microbiota during early life follows relatively predictable trajectories across several mammalian species, largely driven by maternal transmission routes. However, birds lack these transmission mechanisms due to their oviparity, potentially leading to different age-related microbiota patterns. Here, we investigate gut microbiota variation in Atlantic puffin (Fratercula arctica) chicks and adults across six British populations using 16S rRNA amplicon sequencing. We find that chick microbiotas show strong population-level structuring that disappears in adults, with spatial patterns particularly pronounced in anaerobic bacteria. Puffin microbiotas become increasingly individualised and aerotolerant with age, while taxonomic richness remains stable - patterns that contrast with the convergent, richness-increasing trajectories observed in several mammalian species. Our results suggest that environmental exposure drives early-life microbiota assembly in birds, highlighting the value of avian systems for understanding vertebrate microbiota development beyond mammals.

ecology↗

bioRxiv2025

Ectopic expression of the sensor CovS cytosolic domain confers phosphatase activity and full virulence to the M1T1 CovSY39H attenuated variant of group A Streptococcus

Group A Streptococcus (GAS) causes a wide variety of diseases ranging from mild, noninvasive, such as pharyngitis and impetigo, to life-threatening infections, such as necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). The two-component CovR/S system, comprising the sensor kinase CovS and transcription factor CovR, is a central regulator of GAS virulence. An attenuated pharyngeal colonizing variant (S126) possessing a single-nucleotide polymorphism (SNP) in CovS (Y39H) was recovered in France from a member of a family in which another individual developed NF and STSS caused by the M1T1 WT strain (S119). We employed transcriptome analyses (RNA-seq), quantitative determinations of CovR phosphorylation, measurements of virulence factor activity, and a murine model of human NF to demonstrate that CovS of strain S126 almost lost its entire phosphatase activity but retained its kinase and phosphotransfer activities. Moreover, we reversed its attenuated phenotype by ectopically expressing the cytosolic domain of wild-type CovS. Culturing the corresponding strain S126covS-3 in a chemically defined medium (CDM) supplemented with asparagine (Asn), conditions that produce an excess of cytosolic ADP over ATP, stimulated the ectopically expressed phosphatase activity. Consequently, this led to dephosphorylation of CovR[~]P and increased the expression of virulence factors. Most importantly, S126covS-3 reverted to the wild-type phenotype of S119 in the mouse model of human GAS NF. Our study provides a new mechanistic tool that enables the manipulation of CovS phosphatase activity both in vitro and in vivo. IMPORTANCEThe shift from high to low virulence and back in GAS is critical for understanding its pathogenesis and developing new treatments to control GAS infections. The two-component CovR/S system, comprising the sensor kinase/phosphatase CovS and the transcription regulator CovR, regulates the degree of GAS virulence. In the M1T1 serotype, covR/S mutations are typically associated with a loss of CovR/S function, leading to hypervirulent phenotypes. However, an attenuated pharyngeal-colonizing variant possessing a single-nucleotide polymorphism (SNP) in CovS (Y39H strain S126) was isolated in France. Here, we demonstrate that S126 is attenuated because the mutation in CovS inhibits its phosphatase activity but preserves its kinase and phosphotransfer activities. By expressing the cytosolic domain of WT CovS in the S126 background, we endowed the resulting strain, S126covS-3, with phosphatase activity, which was further stimulated by ADP when formed in chemically defined medium (CDM) supplemented with asparagine (Asn). Most importantly, S126covS-3 switched to full virulence, similar to that of S119 in a mouse model of human GAS NF. These findings underscore the importance of comprehensive analyses of disease-related covR/S mutants in understanding the virulence and persistence of GAS.

microbiology↗

bioRxiv2024

Asparagine couples group A Streptococcal metabolism to virulence

Streptococcus (GAS) is a highly adapted and human-restricted pathogen causing a wide variety of infections, some life-threatening1. This ability is linked to the expression of many virulence factors, whose transcription is regulated by the two-component system, CovR/S2-5. Here, we show that genome transcription of GAS cultured in a chemically defined medium (CDM) is globally affected when supplemented with asparagine (Asn), including increased expression of many virulence genes. For the first time, we report that GAS solely depends on asparagine synthetase (AsnA) for Asn synthesis, on the ABC transporter (GlnPQ) to import Asn, and on the asparaginase (AsnB) to maintain a precisely balanced intracellular Asn concentration. Furthermore, we show that mutants defective in either asnA, glnP, or asnB express significantly lower levels of virulence factors in CDM and are severely attenuated in the sublethal murine model of human GAS soft-tissue infection. We further show that the synthesis and import of Asn in GAS are ATP-dependent and negatively regulated by intracellular Asn. Thus, Asn availability controls the intracellular ATP level. When ATP becomes limiting, CovR phosphorylation decreases. This augments GAS growth rate, virulence production, metabolism, and vice versa when the ATP level increases. Furthermore, excess Asn accumulates inside GAS in AsnB mutant, destroying the balance between Asn and ATP. We discuss the high similarity between these mechanistic principles of the Asn-mediated control of GAS virulence and metabolism to the Asn-mediated control of tumor growth6, indicating evolutionary significance.

microbiology↗

bioRxiv2023

Elevated epigenetic age in wild compared to lab-raised house mice

Age is a key parameter in population ecology, with a myriad of biological processes changing with age as organisms develop in early life then later senesce. As age is often hard to accurately measure with non-lethal methods, epigenetic methods of age estimation (epigenetic clocks) have become a popular tool in animal ecology, and are often developed or calibrated using captive animals of known age. However, studies typically rely on invasive blood or tissue samples, which limits their application in more sensitive or elusive species. Moreover, few studies have directly assessed how methylation patterns and epigenetic age estimates compare across environmental contexts (e.g., captive or lab-based vs. wild animals). Here, we built a targeted epigenetic clock from laboratory house mice (strain C57BL/6, Mus musculus) using DNA from non-invasive faecal samples, and then used it to estimate age in a population of wild mice (Mus musculus domesticus) of unknown age. This lab mouse-derived epigenetic clock accurately predicted adult wild mice to be older than juveniles, and showed that wild mice typically increased in epigenetic age over time, but with wide variation in epigenetic ageing rate among individuals. Our results also suggested that, for a given body mass, wild mice had higher methylation across targeted CpG sites than lab mice (and consistently higher epigenetic age estimates as a result), even among the smallest, juvenile mice. This suggests wild and lab mice may display different CpG methylation levels from very early in life, and indicates caution is needed when developing epigenetic clocks on lab animals and applying them in the wild.

molecular biology↗

bioRxiv2023

Early-life gut microbiota assembly patterns are conserved between laboratory and wild mice

Assembly of the mammalian gut microbiota during early life is known to shape key aspects of organismal development, including immunity, metabolism and behaviour. While house mice (Mus musculus) are the major laboratory model organism for gut microbiota research, their artificial lab-based lifestyle could fundamentally alter ecological processes of microbiota assembly and dynamics, in ways that affect their usefulness as a model system. To examine this, here we directly compared patterns of gut microbiota assembly in house mice from the lab and from the wild, making use of a tractable, individually-marked wild population where we could examine patterns of gut microbiota assembly during early life. Despite lab and wild mice harbouring taxonomically distinct communities, we identify striking similarities in multiple patterns of their gut microbiota assembly. Specifically, age-related changes in both alpha and beta diversity, as well as the abundance of predominant phyla and aerotolerance of the microbiota followed parallel trajectories in both settings. These results suggest some degree of intrinsic programme in gut microbiota assembly that transcends variation in taxonomic profiles, and the genetic and environmental background of the host. They further support the notion that despite their artificial environment, lab mice can provide meaningful insights into natural microbiota ecological dynamics in early life and their interplay with host development.

ecology↗

bioRxiv2023

Type VII secretion system and its effect on Group B Streptococcus virulence

GBS may cause a devasting disease in newborns. In early onset disease of the newborn the bacteria are acquired from the colonized mother during delivery. We characterized type VII secretion system (T7SS), exporting small proteins of the WXG100 superfamily, in group B Streptococci (GBS) isolates from pregnant colonized women and newborns with early onset disease (EOD) to understand better understand T7SS contribution to virulence in these different clinical scenarios. GBS isolates were obtained from colonized mother prior to delivery and from newborns with EOD. DNA was analyzed for T7SS genes. A mutant EOD strain (ST17) was created by knocking out the essC gene encoding a T7SS protein. Galleria mellonella larvae were used to compare virulence of colonizing, EOD, and mutant EOD isolates. 33 GBS genomes were tested, 17 EOD isolates and 16 colonizing isolates. The T7SS locus encoded 8 genes: essC, membrane-embedded proteins (essA; essB), modulators of T7SS activity (esaA; esaB; esaC) and effectors: [esxA (SAG1039); esxB (SAG1030). ST17 isolates encode two copies of the essC gene and esxA gene encoding putative effectors but were present only in 23.5% of isolates. In ST1 isolates three copies of esxA gene were identified, but in ST6 and ST19 isolates all T7SS genes were missing. EOD isolates demonstrated enhanced virulence in G. mellonella model compared to colonizing isolates. The 118659{Delta}essC strain was attenuated in its killing ability, and the larvae were more effective in eradicating 118659{Delta}essC infection. essC gene deletion was associated with reduced bacterial growth. We demonstrated that T7SS plays an essential role during infection and contributes to GBS pathogenicity. Author SummaryType VII secretion system (T7SS) is related to virulence in various bacteria but is not well characterized in Group B Streptococci (GBS). GBS may cause sepsis, meningitis, and death in newborns. The bacteria rarely cause disease in pregnant mothers. Newborns acquire GBS from the colonized mother during delivery. We studied the role of T7SS in GBS isolates obtained from newborns with GBS sepsis in the first week of life and in colonized pregnant mothers. By studying T7SS genes we discovered that the genetic structure of the T7SS differs between isolates causing severe disease and colonizing isolates. To study the virulence of different GBS isolates we injected them into larvae and monitored larvae survival. Isolates causing severe disease in the newborn caused a more severe disease in larvae compared to colonizing isolates. We then deleted T7SS genes in GBS isolates causing severe disease. The killing activity of GBS isolates without T7SS genes was attenuated. The larva responded to these bacteria similarly to the response found when injecting the larva with GBS isolates from colonized mothers. These results support our hypothesis that T7SS is important for causing severe infection in the newborn and that this system contributes to GBS pathogenicity.

microbiology↗

bioRxiv2017

Streptolysin-induced endoplasmic reticulum stress promotes group A streptococcal in vivo biofilm formation and necrotizing fasciitis

Group A Streptococcus (GAS) is a human pathogen that causes infections ranging from mild to fulminant and life-threatening. Biofilms have been implicated in acute GAS soft-tissue infections such as necrotizing fasciitis (NF). However, most in vitro models used to study GAS biofilms have been designed to mimic chronic infections and insufficiently recapitulate in vivo conditions and the host-pathogen interactions that might influence biofilm formation. Here we establish and characterize an in vitro model of GAS biofilm development on mammalian cells that simulates microcolony formation observed in a murine model of human NF. We show that on mammalian cells, GAS forms dense aggregates that display hallmark biofilm characteristics including a three-dimensional architecture and enhanced tolerance to antibiotics. In contrast to abiotic-grown biofilms, host-associated biofilms require the expression of secreted GAS streptolysins O and S (SLO, SLS) resulting in the release of a host-associated biofilm promoting-factor(s). Supernatants from GAS-infected mammalian cells or from cells treated with endoplasmic reticulum (ER) stressors restore biofilm formation to an SLO and SLS null mutant that is otherwise attenuated in biofilm formation on cells, together suggesting a role for streptolysin-induced ER stress in this process. In an in vivo mouse model, the streptolysin-null mutant is attenuated in both microcolony formation and bacterial spread, but pre-treatment of softtissue with an ER-stressor restores the ability of the mutant to form wild type like microcolonies that disseminate throughout the soft tissue. Taken together, we have identified a new role of streptolysin-driven ER stress in GAS biofilm formation and NF disease progression.\n\nSignificance StatementAlthough it is well-accepted that bacterial biofilms are associated with many chronic infections, little is known about the mechanisms by which group A Streptococcus (GAS) biofilms contribute to acute soft tissue-invasive diseases like necrotizing fasciitis (NF). In this study, we establish a physiologically relevant in vitro model to study GAS biofilm formation on mammalian cells and validate our findings in a mouse model that mimics human NF. This study demonstrates a novel role of GAS streptolysin-mediated ER stress in the development and spread of GAS biofilms in acute softtissue infections. We also show that biofilm formation depends on the release of a host-associated factor that promotes microcolony formation and GAS dissemination in vivo.

microbiology↗