Biology subjects

Recker, M.

Publications and source records attributed to Recker, M..

13 recordsLinked to original sources

bioRxiv2026

An Eco-Evolutionary Modelling Framework for Mosquito Host Specialisation

Host preference varies widely across mosquitoes, with many species feeding opportunistically on diverse vertebrate hosts, while others show strong fidelity to specific hosts. Anthropophilia, the behavioural preference for feeding on humans, is a defining characteristic of some mosquito species responsible for the transmission of major human diseases, including malaria, dengue, and yellow fever. The evolution of anthropophilia therefore has profound epidemiological implications because increased human biting elevates vectorial capacity and disease transmission potential. However, the ecological and evolutionary mechanisms driving this extreme specialisation have not yet been fully elucidated and remain difficult to unify across laboratory and field studies. Here we present an eco-evolutionary modelling framework that links genetically determined mosquito traits with spatially structured host environments. Our framework integrates innate olfactory sensitivity, blood meal-derived fitness benefits, and spatio-temporal host accessibility. Two complementary indices are introduced: a local specialisation index, capturing short-term ecological feeding strategies, and a co-evolutionary index, capturing long-term genetic coupling between host detection and resource utilisation. Our results demonstrate that host specialisation is not a default evolutionary outcome but an environmentally gated process, which is favoured in resource-poor or temporally varying habitats and strongly filtered by seasonality. The framework yields testable predictions regarding when specialisation emerges, persists, or collapses, with direct implications for predicting vector-borne disease risk in changing environments

evolutionary biology↗

bioRxiv2026

SELECT 2.0: Refined and open access SELection Endpoints in Communities of bacTeria (SELECT) method to determine concentrations of antibiotics that may select for antimicrobial resistance in the environment

Antimicrobial resistance (AMR) is a significant and growing threat to human, plant and animal health, the global economy, and food security. The One Health approach to AMR recognises the role of the environment in the evolution, emergence, and dissemination of AMR. In part, this is due to anthropogenic pollution that releases AMR organisms alongside cocktails of compounds that may select for AMR in situ, which then pose an exposure risk to humans and animals. This has spurred growing interest from cross-sectoral stakeholders in environmental risk assessment (ERA) of antibiotics, with regards to their selective potential. Many different experimental and modelling approaches have been used to determine the lowest concentration of an antibiotic that may select for AMR. Debates continue regarding which individual approach, if any, may be best for determining concentrations of antibiotics that may select for AMR, for ERA purposes. This paper contributes to this ongoing discourse by refining and using a previously published method SELECT (SELection Endpoints in Communities of bacTeria) to rapidly generate predicted no effect concentrations for resistance (PNECRs) for 32 antibiotics on the premise that reduction in growth of complex community of bacteria correlates with selection for AMR resistance genes. The database of PNECRs of antibiotics presented here is the largest generated using a single experimental, empirical approach that will aid future efforts towards creating a standardised test. PNECR data were used to conduct ERAs using measured environmental concentrations of antibiotics to rank antibiotics by potential selection risk in different environments. The experimental approach and statistical code have been made open access, with online tutorials available to facilitate other laboratories using the SELECT 2.0 method. Finally, we discuss the limitations of this approach and how these could be addressed in future studies.

microbiology↗

bioRxiv2026

Copper as a central element critical to interkingdom interactions within a polymicrobial wound environment.

Staphylococcus aureus is a global health concern, estimated to cause over one million deaths each year. To colonise and survive in humans, S. aureus must overcome the host-immune system and compete with other native and invading microorganisms. As a frequent coloniser of wounds, it forms inter-kingdom polymicrobial biofilms, which are associated with impaired wound healing and poorer clinical outcomes. However, the microbial processes that contribute to the competitiveness of S. aureus within infection-related inter-kingdom communities are poorly understood. To address this, we established a polymicrobial in vitro wound-like model (WLM) consisting of two common bacterial pathogens Staphylococcus aureus and Pseudomonas aeruginosa, as well as a the fungal pathobiont Candida albicans. Using a collection of clinical S. aureus strains we then applied a genome-wide association study (GWAS) approach to identify bacterial factors that contribute to S. aureus fitness within this environment. Amongst the six S. aureus loci identified was copA, which encodes a copper exporter that prevents the accumulation of copper in the bacterial cytoplasm. Characterising the molecular processes involved, we identified a 4-way interaction, where C. albicans releases copper from the ceruloplasmin found in the human hosts plasma, which in turn causes a build-up of copper within the S. aureus cytoplasm, rendering the bacteria more susceptible to killing by P. aeruginosa. Human infection data validates the clinical relevance of this, where there is an association between mutations in copA and an origin of infection that is wound-based, highlighting the importance of understanding the entire infection ecosystem if improvements therapeutic approaches are to be developed.

microbiology↗

bioRxiv2025

Eco-evolutionary feedbacks drive the co-occurrence of restriction-modification systems and antimicrobial resistance genes

Bacterial pathogens commonly become drug resistant via horizontal acquisition of antimicrobial resistance genes (ARGs), which are often encoded on mobile genetic elements (MGEs). Although bacterial defence systems are typically considered barriers to horizontal gene transfer (HGT), previous studies revealed that bacteria with more restriction-modification (RM) systems (the most abundant bacterial defences) frequently carry more MGEs. It was suggested that this counterintuitive relationship might result from stronger selection for RM systems when exposure to costly MGEs increases. Here, we test this hypothesis using a combination of modelling and bioinformatics analysis of >40,000 bacterial genomes to better understand how eco-evolutionary feedbacks between selection for RM and acquisition of MGEs shape bacterial genome evolution. Our model predicts negative associations between HGT and RM, but only if RM diversity is high. By contrast, at low RM diversity, eco-evolutionary feedbacks drive the emergence of positive associations between HGT and RM. Consistent with these predictions, we identified negative relationships between acquired ARG counts and RM counts across species but positive relationships within individual species. Collectively, our work helps to understand how RM systems shape patterns of HGT of ARGs, which may offer opportunities for targeted surveillance of strains at higher risk of horizontally acquiring novel drug resistance alleles. Significance statementPrevious research shows positive associations between bacterial restriction-modification (RM) systems and mobile genes, despite RM being well-evidenced as a barrier to mobile gene acquisition. Eco-evolutionary feedbacks have been hypothesised to drive this; higher HGT exposure will select for greater RM investment, while still leading to increased mobile gene acquisition. By formalising this hypothesis into a mathematical model and analysing bacterial genomes, we reveal novel insights into how the relationship between RM and mobile antimicrobial resistance genes (ARGs) depends on ecological variables. This study illustrates that to better comprehend how defence systems regulate gene transfer in natural communities, it is essential to consider both their mechanisms and the complex eco-evolutionary dynamics at play.

microbiology↗

bioRxiv2025

Expression of mecA reduces the daptomycin susceptibility of Staphylococcus aureus

Staphylococcus aureus is a leading cause of bacteraemia and infections caused by methicillin-resistant strains (MRSA) are especially challenging to treat. MRSA strains are resistant to front-line beta-lactams due to PBP2a, a low-affinity penicillin-binding protein encoded by mecA. Daptomycin is used to treat MRSA infections but is not always effective and is associated with high rates of morbidity and mortality. Understanding why daptomycin fails is crucial to devising strategies to improve treatment outcomes. Here, using a panel of clinical bacteraemia isolates, we show that MRSA strains are less susceptible to daptomycin than methicillin-susceptible (MSSA) strains. This difference in susceptibility was due to mecA and was independent of any changes in surface properties previously associated with altered daptomycin susceptibility. Instead, using a mecA transposon mutant, we found that a lack of this gene led to higher activity of the Agr quorum sensing system, resulting in an increased release of the phenol-soluble modulin toxins. Increased levels of these surfactant-like toxins prevented daptomycin from being inactivated by lipids released by the bacteria, leading to enhanced susceptibility to the antibiotic. Additionally, the clinical MRSA strains tested produced lower levels of toxins than the MSSA strains and inactivated daptomycin to a greater extent, explaining their reduced susceptibility. Expression of mecA in clinical MSSA strains reduced toxin production, increasing daptomycin inactivation and thereby enhancing survival. Together, these results demonstrate that mecA does not only affect beta-lactam susceptibility but also compromises the efficacy of the last resort antibiotic daptomycin.

microbiology↗

bioRxiv2023

Extensive re-modelling of the cell wall during the development of Staphylococcus aureus bacteraemia

Introductory Paragraph / AbstractThe bloodstream represents a hostile environment that bacteria must overcome to cause bacteraemia. To understand how the major human pathogen Staphylococcus aureus manages this we have utilised a functional genomics approach to identify a number of new loci that affect the ability of the bacteria to survive exposure to serum, the critical first step in the development of bacteraemia. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, and we show that it is involved in the elaboration of a critical virulence factor, the wall teichoic acids (WTA), within the cell envelope. The activity of the TcaA protein alters the sensitivity of the bacteria to cell wall attacking agents, including antimicrobial peptides, human defence fatty acids, and several antibiotics. This protein also affects the autolytic activity and lysostaphin sensitivity of the bacteria, suggesting that in addition to changing WTA abundance in the cell envelope, it also plays a role in peptidoglycan crosslinking. With TcaA rendering the bacteria more susceptible to serum killing, while simultaneously increasing the abundance of WTA in the cell envelope, it was unclear what effect this protein may have during infection. To explore this, we examined human data and performed murine experimental infections. Collectively, our data suggests that whilst mutations in tcaA are selected for during bacteraemia, this protein positively contributes to the virulence of S. aureus through its involvement in altering the cell wall architecture of the bacteria, a process that appears to play a key role in the development of bacteraemia.

microbiology↗

bioRxiv2021

Self-sensitisation of Staphylococcus aureus to the antimicrobial factors found in human blood.

Introductory ParagraphFor opportunistic pathogens, the switch from a commensal to an invasive lifestyle is often considered an accidental event. But with plentiful opportunity, what leads one accidental event to result in an invasive infection, and another not to? And how much of this apparent stochasticity is driven by bacterial factors? To answer these questions, here we focussed on the major human pathogen Staphylococcus aureus, which can both reside asymptomatically as a member of our respiratory microbiome, or become invasive and cause infections as severe as bacteraemia. Survival upon exposure to the antibacterial factors found in serum is a critical aspect of their ability to cause bacteraemia, and across a collection of 300 clinical isolates we found there to be significant variability in this capability. Utilising a GWAS approach we have uncovered the genetic basis of much of this variability through the identification and functional verification of a number of new polymorphic loci that affect serum survival: tcaA, tarK, gntR, ilvC, arsB, yfhO, and pdhD. The expression of one of these genes, tcaA, was found to be induced upon exposure to serum, while simultaneously enhancing the sensitivity of S. aureus to serum through a process involving the ligation of wall teichoic acids into the cell wall. As blood-stage infections are a transmission dead-end for the bacteria, that S. aureus actively responds to serum to produce a protein which specifically limits their ability to survive in this environment demonstrates that the switch from the commensal to the invasive lifestyle is complex, and that TcaA may contribute to the long-term success of S. aureus by restricting the bacteria to their more readily transmissible commensal state.

microbiology↗

bioRxiv2021

A Functional Menadione Biosynthesis Pathway is Required for Capsule Production by Staphylococcus aureus.

Staphylococcus aureus is a major human pathogen that utilises a wide array of pathogenic and immune evasion strategies to cause disease. One immune evasion strategy, common to many bacterial pathogens, is the ability of S. aureus to produce a capsule that protects the bacteria from several aspects of the human immune system. To identify novel regulators of capsule production by S. aureus we applied a genome wide association study (GWAS) to a collection of 300 bacteraemia isolates that represent the two major MRSA clones in UK and Irish hospitals: CC22 and CC30. One of the loci associated with capsule production, the menD gene, encodes an enzyme critical to the biosynthesis of menadione. Mutations in this gene that result in menadione auxotrophy induce the slow growing small-colony variant (SCV) form of S. aureus often associated with chronic infections due to their increased resistance to antibiotics and ability to survive inside phagocytes. Utilising such an SCV we functionally verified this association between menD and capsule production. Although the clinical isolates with polymorphisms in the menD gene in our collections had no apparent growth defects, they were more resistant to gentamicin when compared to those with the wild-type menD gene. Our work suggests that menadione plays a critical role in the production of the S. aureus capsule, and that amongst clinical isolates polymorphisms exist in the menD gene that confer the characteristic increased gentamicin resistance, but not the major growth defect associated with SCV phenotype.

microbiology↗

bioRxiv2019

Inferring the ecological drivers of arboviral outbreaks

The emergence and wide-spread circulation of mosquito-transmitted viral diseases, such as dengue, Zika and Chikungunya, is a global public health concern. In the absence of effective vaccines, current control measures are mostly targeted against the mosquito vector and have so far only shown limited success. The reliance on mosquitoes for transmission also imposes strong ecological constraints that can introduce significant spatial and temporal variations in disease incidence. However, the way that epidemiological and ecological factors interact and determine population-level disease dynamics is only partially understood. Here we fit a spatially-explicit individual based model defined within a Bayesian framework to Zika incidence data from Feira de Santana, allowing us to more precisely quantify the relationships between socio-ecological factors and arboviral outbreaks. Our results further demonstrated that the virus was likely introduced into multiple spatially segregated locations at the start of the outbreak, highlighting the benefits that spatio-temporal incidence data would bring in making modelling approaches more realistic for public health planning.

epidemiology↗

bioRxiv2019

Selection for antibiotic resistance is reduced when embedded in a natural microbial community

Antibiotic resistance has emerged as one of the most pressing, global threats to public health. In single-species experiments selection for antibiotic resistance occurs at very low antibiotic concentrations. However, it is unclear how far these findings can be extrapolated to natural environments, where species are embedded within complex communities. We competed isogenic strains of Escherichia coli, differing exclusively in a single chromosomal resistance determinant, in the presence and absence of a pig fecal microbial community across a gradient of antibiotic concentration for two relevant antibiotics: gentamicin and kanamycin. We show that the minimal selective concentration was increased by more than one order of magnitude for both antibiotics when embedded in the community. We identified two general mechanisms were responsible for the increase in minimal selective concentration: an increase in the cost of resistance and a protective effect of the community for the susceptible phenotype. These findings have implications for our understanding of the evolution and selection of antibiotic resistance, and can inform future risk assessment efforts on antibiotic concentrations.

microbiology↗

bioRxiv2017

Multi-scale immune selection and the transmission-diversity feedback of Plasmodium falciparum malaria

Antigenic diversity is a key factor underlying the complex epidemiology of Plasmodium falciparum malaria. Within-host clonal antigenic variation limits host exposure to the parasites antigenic repertoire, while the high degree of diversity at the population-level requires multiple exposures for hosts to acquire anti-disease immunity. This diversity is predominantly generated through mitotic and meiotic recombination between individual genes and multi-gene repertoires and is therefore expected to respond dynamically to changes in transmission and immune selection. We hypothesised that this coupling creates a positive feedback mechanism whereby infection and disease transmission promotes the generation of diversity, which itself facilitates immune evasion and hence further infection and transmission. To investigate the link between diversity and malaria prevalence in more detail we developed an individual-based model in which antigenic diversity emerges as a dynamic property from the underlying transmission processes. We show that the balance between stochastic extinction and the generation of new antigenic variants is intrinsically linked to within-host and between-host immune selection, which in turn determines the level of diversity that can be maintained in a given population. We further show that the transmission-diversity feedback can lead to temporal lags in the response to natural or intervention-induced perturbations in transmission rates. These results will add to our understanding of the epidemiological dynamics of P. falciparum malaria in different transmission settings and will have important implications for monitoring and assessing the effectiveness of disease control efforts.

epidemiology↗

bioRxiv2017

Epistasis mediated alleviation of the cost of antibiotic resistance for MRSA

Understanding how multi-drug resistant pathogens evolve is key to identifying means of curtailing their further emergence and dissemination. Fitness costs imposed on bacteria by resistance mechanisms are believed to hamper their dissemination in an antibiotic free environment, however, some have been reported to have little or no cost, which suggests there are few barriers preventing their global spread. One such apparently cost-free resistance mechanism acquired by the major human pathogen Staphylococcus aureus is to the clinically important antibiotic mupirocin, which is mediated by mutation of the highly-conserved and essential isoleucyl-tRNA synthethase (ileS) gene. In Genome Wide Association Studies (GWAS) on two genetically and geographically distinct MRSA lineages we have found this mutation to be associated with changes in bacterial virulence, driven through epistatic interactions with other loci. Given the potential dual effect of this mutation on both antibiotic resistance and virulence we adopted a proteomic approach and observed pleiotropic effects. This analysis revealed that the activity of the secretory apparatus of the PSM family of cytolytic toxins, the Pmt system, is affected in the mupirocin resistant mutant, which explains why it is less toxic. As an energetically costly activity, this reduction in toxicity masks the fitness costs associated with this resistance mutation, a cost that becomes apparent when toxin production is required. Given the widespread use of this antibiotic, and that this resistance often results from a single nucleotide substitution in the ileS gene, these hidden fitness costs provide an explanation for why this resistance mechanism is not more prevalent. This work also demonstrates how population-based genomic analysis of virulence and antibiotic resistance can contribute to uncovering hidden features of the biology of microbial pathogens.

microbiology↗

bioRxiv2017

Epidemiological and ecological determinants of Zika virus transmission in an urban setting.

Zika has emerged as a global public health concern. Although its rapid geographic expansion can be attributed to the success of its Aedes mosquito vectors, local epidemiological drivers are still poorly understood. The city of Feira de Santana played a pivotal role in the early phases of the Chikungunya and Zika epidemics in Brazil. Here, using a climate-driven transmission model, we show that low Zika observation rates and a high vectorial capacity in this region were responsible for a high attack rate during the 2015 outbreak and the subsequent decline in cases in 2016, when the epidemic was peaking in the rest of the country. Our projections indicate that the balance between the loss of herd-immunity and the frequency of viral re-importation will dictate the transmission potential of Zika in this region in the near future. Sporadic outbreaks are expected but unlikely to be detected under current surveillance systems.

epidemiology↗