RESEARCH

The relationship between the ecology and evolution of bacterial pathogens

Bacterial pathogens are capable of rapidly adapting to changes in their environment. This allows them to infect new host species, evolve resistance to antibiotic treatments, and evade vaccines. My research aims at understanding:

the impact ecology has on the evolutionary dynamics of pathogens, and
evolutionary constraints on the adaptation of pathogens to new environments and ecologies.

The study of pathogens often focusses on the disease state, but pathogens often colonise their hosts without causing disease and persist in external environments. These states can be central to the transmission and persistence of pathogens, and can shape pathogen evolution. I'm interested in the relationship between adaptation in these non-disease contexts and the evolution of pathogenicity and antibiotic resistance.

My research involves investigating the relationship between ecology and evolution within and between bacterial species; comparing pathogens to close commensal or less-pathogenic relatives, multi-host pathogens across different host species, and disease-associated populations to carriage populations.

My recent work has involved investigating the link between genome size, mutation rate and pathogenicity, and the drivers of and constraints on transitions from a commensal to pathogenic ecology.

In this recent study we demonstrated that bacterial pathogens tend to have smaller genomes and fewer genes than their closest non-pathogenic or less-pathogenic relatives. We found that this pattern held in comparisons across species, and within species between both genetic clusters and individual isolates. We suggest that genome reduction could prove a useful marker of emerging and increasing pathogenicity.

In another recent study we found evidence that the global transport of live pigs has facilitated the emergence of an important livestock and human zoonotic pathogen from a common member of the pig respiratory microbiota. Our results suggest that pathogenic lineages are likely to continue to emerge and diversify and recommend ways of controlling this. We identified genetic markers of pathogenic lineages, and are working with collaborators at the University of Wageningen to functionally characterise them and use them to develop tests for surveillance and control.

The role of commensals in pathogen evolution

When pathogens are carried asymptomatically by a host they often live side-by-side with commensal members of the host's microbiota. This creates an opportunity for horizontal gene transfer between commensals and pathogens, and while it is known that gene transfers occur, the role they play in pathogen evolution remains poorly understood.

Antibiotic Resistance

While commensal bacteria are not the target of antibiotic treatments, they may evolve resistance to antibiotics through a ‘bystander’ effect, whereby they are inadvertently exposed to antibiotics during the treatment of an infection. Resistance in commensal bacteria can promote the emergence of resistance in pathogens as resistance genes can be transferred between bacterial cells, even across different species. These transfers are most likely to occur when the donor and recipient inhabit the same environment, and are close relatives.

My research aims to understand how resistance emerges and spreads through commensal bacterial populations, and how it is transferred to pathogens. My focus is particularly on opportunistic pathogens that spend extended periods of time being carried by healthy hosts, and their close commensal relatives in the microbiome.

Host-switching

Most emerging human pathogens are zoonotic in origins, i.e. they originate in another animal species. Commensal bacteria tend to be well adapted to colonise a specific host species, and may therefore act as a source of genes that allow a novel pathogen to adapt to that species, therefore facilitating cross-species transmission. As with antibiotic resistance genes, my research aims at understanding the role of commensal populations in the adaptation of pathogens to novel hosts.

The impact of purifying selection on evolutionary rates and population structure

It is widely accepted that molecular dating using ‘dated-tip’ methods can result in the overestimation of long-term evolutionary rates due to the gradual removal of weakly deleterious mutations. Low rates of recombination can lead to interference between sites under selection, and therefore to slower removal of weakly deleterious mutations. These dynamics are difficult to predict, and can not only lead to variation in evolutionary rates over a phylogeny, but also to changes in the depth and shape of a phylogeny. While these effects may be observed across a wide range of taxonomic groups, they are likely to be particularly evident in bacteria due to their often low rates of recombination and large population sizes.

With collaborators at the University of Cambridge I am investigating the impact of weakly deleterious mutations on the evolutionary dynamics of bacterial populations using both simulations and empirical analyses. This could have important consequences for our dating of the origins of bacterial pathogens, and our interpretation of the drivers of genetic diversity within pathogens.

The dynamics of mobile genetic elements

Mobile genetic elements promote the transfer of genes between bacterial cells and sometimes between different species. They often carry genes associated with virulence, antibiotic resistance, and adaptation to different host species. While these elements are known to be important in the evolution of bacterial pathogens, their evolutionary dynamics are rarely characterised. This is an important gap in our understanding of adaptive evolution in bacteria, as rates of gain and loss can inform about the selective benefits and costs of these elements, and their availability for acquisition in different ecological contexts.

In a recent study we explored the dynamics of mobile genetic elements in the dominant MRSA in European livestock.

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