Biology subjects

Matuszewska, M.

Publications and source records attributed to Matuszewska, M..

7 recordsLinked to original sources

bioRxiv2025

Mutational spectra reveal influenza virus transmission routes and adaptation

Influenza A virus remains a major cause of morbidity and mortality in humans and animals with pandemic potential. While control of outbreaks and spillover events remains a key health priority, the transmission routes and adaptations causing these episodes remain unclear. To understand these processes, we compared mutational spectra across the complete diversity of influenza A virus. We find that niche-specific mutagens cause large convergent shifts in mutational spectrum between gastrointestinal and respiratory lineages, allowing inference of transmission route and site of infection, while additional mutational patterns are host-specific, permitting detection of species responsible for outbreaks. By identifying points of spectrum change in phylogenetic trees, we discover novel adaptive mutations enabling sustained respiratory transmission. We conclude that mutational spectra can enable early detection of lineages with increased potential for spillover and onward transmission, and should be considered as a component of genomic surveillance strategies.

microbiology↗

bioRxiv2025

BET protein inhibitor JQ1 reduces inflammation and hippocampal amyloid-β level without altering Tau phosphorylation in LPS-challenged adult wild-type mice

IntroductionA growing body of evidence highlights the role of infection and inflammation in the progression of Alzheimers disease (AD). In this study, we aimed to analyze the impact of JQ1, an inhibitor of bromodomain and extraterminal domain (BET) proteins, which are key readers of the epigenetic acetylation code, on AD-related gene expression changes and biochemical alterations in the hippocampus during a lipopolysaccharide (LPS)-induced systemic inflammatory response in mice. MethodsJQ1 and LPS were administered intraperitoneally to adult male wild-type C57BL/6J mice. Changes in selected general and brain-specific parameters were measured for up to 12 h. ResultsOur results demonstrated that inhibition of BET proteins reduced LPS-induced sickness behavior and time-dependent elevation of proinflammatory signaling. LPS did not significantly alter amyloid-{beta} (A{beta}) levels; however, a significant reduction in A{beta} load was observed in JQ1-treated animals overall, suggesting that BET proteins play a crucial role in regulating A{beta} levels in the brain. At the same time, JQ1 treatment did not affect LPS-induced increases in phospho-Tau levels. DiscussionOur results suggest that inhibiting BET proteins, in addition to their anti-inflammatory action, may be an effective strategy for reducing A{beta} levels in the brain. However, a mechanistic explanation of this phenomenon requires further investigation.

neuroscience↗

bioRxiv2023

The mutational landscape of Staphylococcus aureus during colonisation

Staphylococcus aureus is an important human pathogen but is primarily a commensal of the human nose and skin. Survival during colonisation is likely one of the major drivers of S. aureus evolution. Here we use a genome-wide mutation enrichment approach to analyse a genomic dataset of 3,060 S. aureus isolates from 791 individuals to show that despite limited within-host genetic diversity, an excess of protein-altering mutations can be found in genes encoding key metabolic pathways, in regulators of quorum-sensing and in known antibiotic targets. Nitrogen metabolism and riboflavin synthesis are the metabolic processes with strongest evidence of adaptation. Further evidence of adaptation to nitrogen availability was revealed by enrichment of mutations in the assimilatory nitrite reductase and urease, including mutations that enhance growth with urea as the sole nitrogen source. Inclusion of an additional 4,090 genomes from 802 individuals revealed eight additional genes including sasA/sraP, pstA, and rsbU with signals adaptive variation that warrant further characterisation. Our study provides the most comprehensive picture to date of the heterogeneity of adaptive changes that occur in the genomes of S. aureus during colonisation, revealing the likely importance of nitrogen metabolism, loss of quorum sensing and antibiotic resistance for successful human colonisation.

genomics↗

bioRxiv2023

The emergence and diversification of a zoonotic pathogen from within the microbiota of intensively farmed pigs

The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species this can affect the health of humans as well as livestock. Here we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of Streptococcus suis, a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of S. suis emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of S. suis and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of S. suis is yet to be fully realised.

evolutionary biology↗

bioRxiv2022

Absence of Staphylococcus aureus in wild populations of fish supports a spillover hypothesis

Staphylococcus aureus is a human commensal and opportunistic pathogen that can also colonise and cause disease in other animal species. In humans and livestock, where S. aureus is most studied, there is evidence that strains have different host specialisms. Recent studies have found S. aureus in many wild animals, including fish, whose physiologies and ecologies are very different to humans. However, it remains unclear whether S. aureus is adapted to and persisting within these species, or if its presence is due to repeated spillover from a source population. Distinguishing between these two scenarios is important for both public health and conservation. In this study we looked for evidence to support the hypothesis that the presence of S. aureus in fish is the result of spillover, through testing for the presence of S. aureus in fish that are isolated from likely source populations. We sampled 123 brown trout and their environment from 16 sites in the Scottish Highlands. All these sites are remote and have very low populations density of wild animal species known to carry S. aureus, but were selected to represent variable levels of exposure to humans, avian and livestock species. While our sampling methods readily detected S. aureus from the external and internal organs of a farmed fish, we did not detect S. aureus in any wild trout or their environment from any of the 16 sites. We sequenced 12 S. aureus isolates from the farmed fish. While they were all from clonal-complex 45, the genomic diversity was high enough to indicate repeated acquisition from a source population. In addition, the presence of a {varphi}Sa3 prophage containing a human immune evasion cluster indicates a recent history of these isolates within human populations. Taken together, our results support the presence of S. aureus in fish being due to spillover from other host populations, rather than the adaptation of S. aureus to aquaculture or fish populations. Given predictions that fish consumption will increase, more whole genome sequencing of S. aureus in aquaculture is needed to understand the presence of S. aureus in these environments and to mitigate the risk to fish and human health.

microbiology↗

bioRxiv2021

Half a century of stable antibiotic resistance in livestock-associated Staphylococcus aureus and its dynamic readaptation to humans

Mobile genetic elements (MGEs) are agents of horizontal gene transfer in bacteria, but can also be vertically inherited by daughter cells. Establishing the dynamics that led to contemporary patterns of MGEs in bacterial genomes is central to predicting the emergence and evolution of novel and resistant pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) clonal-complex (CC) 398 is the dominant MRSA in European livestock and a growing cause of human infections. Previous studies have identified three categories of MGEs whose presence or absence distinguishes livestock-associated CC398 from a closely related and less antibiotic-resistant human-associated population. Here we fully characterise the evolutionary dynamics of these MGEs using a collection of 1,180 CC398 genomes, sampled from livestock and humans, over 27 years. We find that the emergence of livestock-associated CC398 coincided with the acquisition of a Tn916 transposon carrying a tetracycline resistance gene, which has been stably inherited for 57 years. This was followed by the acquisition of a type V SCCmec that carries methicillin, tetracycline and heavy metal resistance genes, which has been maintained for 35 years, with occasional truncations and replacements with type IV SCCmec. In contrast, a class of prophages that carry a human immune evasion gene cluster and that are largely absent from livestock-associated CC398, have been repeatedly gained and lost in both human- and livestock-associated CC398. These contrasting dynamics mean that when livestock-associated MRSA is transmitted to humans, adaptation to the human host outpaces loss of antibiotic resistance. In addition, the stable inheritance of resistance-associated MGEs suggests that the impact of ongoing reductions in antibiotic and zinc oxide use in European farms on livestock-associated MRSA will be slow to be realised.

evolutionary biology↗

bioRxiv2021

Mutation rate dynamics reflect ecological changes in an emerging zoonotic pathogen

While mutation is often deleterious, it can also be adaptive. Mutation rates vary both within and between bacterial species, and understanding what drives this variation is essential for understanding the evolutionary dynamics of bacterial populations. In this study we investigate two factors that are predicted to influence the trade-off between the costs and benefits of mutation: ecology and genome size. To investigate the relationship between these factors and mutation rate we conducted mutation accumulation experiments on eight strains of the emerging zoonotic pathogen Streptococcus suis. Natural variation within this species allows us to compare tonsil carriage and invasive disease isolates, from both more and less pathogenic populations, with a wide range of genome sizes. We find that invasive disease isolates have repeatedly evolved mutation rates that are higher than those of closely related carriage isolates, regardless of variation in genome size. Independent of this variation in overall rate, we also observe a stronger bias towards G/C to A/T mutations in isolates from more pathogenic populations, whose genomes tend to be smaller and more AT-rich. Our results suggest that ecology is a stronger correlate of mutation rate than genome size over these timescales, and that transitions to invasive disease are consistently accompanied by rapid increases in mutation rate. These results shed light on the impact ecology can have on the adaptive potential of bacterial pathogens.

evolutionary biology↗