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Abstracts

Talks

- Session 1 -

09:10 - 09:40 Munehiro Asally - University of Warwick.

Signalling through membrane potential dynamics

Bacterial biofilms are structured communities consisting of billions of cells which spatial scale can be in the order of millimeters. It remained largely unclear how bacterial cells are able to communicate in such a long distance. We recently discovered a new form of bacterial interactions mediated by changes in membrane potentials. The electrical signaling via membrane potential dynamics enables the coordination of metabolisms within a biofilm. Enlighted by these findings, we are developing a tool to study the membrane potential dynamics in response to external electrical fields. This device may in the future allow us to interfere with the biofilm electrical communications. Furthermore, I will discuss our recent finding about the role of membrane potential dynamics during bacterial cellular differentiation into spores

09:40 - 10:10 Knut Drescher - Max Planck Institute.

Biofilm-phage interaction dynamics and cell-cell interaction mechanics.

Biofilms are constantly exposed to phages in the natural environment, yet it is largely unknown which mechanisms govern their interactions. I will first present a new microscopy and imaging technique we recently developed to follow dynamical processes in biofilms at the single-cell level. I will then proceed to show how we applied this novel imaging technology in combination with genetics and molecular techniques to discover basic interaction mechanisms of biofilms and phages, how individual cells within biofilms interact with each other, and how biofilms disperse.

10:10 - 10:40 Avigdor Eldar - Tel-Aviv University.

Regaining cooperation in quorum-sensing suppressed mutants of Pseudomonas Aeruginosa.

The opportunistic pathogen P. aeruginosa, employs a hierarchical quorum-sensing network to regulate virulence factor production which cooperatively benefit the population at a cost to the individual. Quorum-sensing suppression was therefore proposed as an attractive anti-virulence target. Furthermore, it was argued that the evolution of a cooperative mutant in a quorum-sensing-suppressed population would be hampered through its exploitation by neighboring non-mutant cells. It remains unclear whether mechanisms which overcome this exploitation exist. We investigated the regain of quorum-sensing cooperation by combining rational design of candidate strains and directed evolution of a mutant of the lasR master quorum-sensing regulator. We find that mutations that act to increase signaling levels are superior to those where reception level is increased. Both of these strategies were less effective than mutations that pleiotropically combined regain of cooperation and private benefit. We find one such mutation which led to significant conflict between regain of cooperation and antibiotic resistance.

- Session 2 -

11:00 - 11:30 Duccio Cavalieri - University of Florence.

Yeast as a model in evolutionary systems biology.

The promise of systems biology to predictively model systems, can be fulfilled only using the knowledge on their evolution to understand how the system optimizes its functions. The comparative analysis of thousands of sequenced yeast genomes enables to measure the traces of selection, and ask how this has been shaping yeast genomes. Yet to understand selection one has to first understand a system’s ecology. Saccharomyces cerevisiae has been the cradle and stage of genomics, systems and synthetic biology, yet its ecological cycle and its interactions are still unknown. Here I will discuss the most recent views on the ecology and evolutionary biology of S.cerevisiae cerevisiae, suggesting that S.cerevisiae blooms during growth in sugar rich ecological niches, but that insects and animal gut are the ecological niches where its life cycle is completed. Further I will discuss the interplay of genetic and epigenetic forces shaping its genome, showing the central role of changes in cell wall to rapidly adapt to different environments, with a dramatic display of genetic plasticity. Finally I will show how changes in cell wall composition can be used to turn the immune systems of the host into a tool to control competitors. These results and experimental approach will prove valuable tools in designing in silico and testing novel Synthetic strains of Saccharomyces cerevisiae. The ability to test predictions building synthetic interactions in model organisms, opens novel revolutionary scientific horizons, but holds important questions on how these newly designed organisms will evolve, interact and compete in ecological niches other than those limited to the lab or the industry.

11:30 - 12:00 Pauline Scanlan - APC Microbiome Institute and School of Microbiology, University College Cork, Ireland.

Towards developing a model system to study bacteria-bacteriophage coevolution in the human gut microbiome.

Antagonistic coevolution (AC) between bacteria and bacteriophages (phages) plays a key role in driving and maintaining microbial diversity. Consequently, AC is predicted to affect all levels of biological organisation, from the individual to ecosystem scales. Nonetheless, we know nothing about bacteria-bacteriophage AC in perhaps the most important and clinically relevant microbial ecosystem known to humankind - the human gut microbiome. Here I discuss data from an in vitro model of AC that exploits the interaction between the gut microbe Escherichia coli and the lytic phage PPO1. More specifically I outline the impact of various abiotic factors (antibiotics, bile, oxygen) on the persistence of coevolutionary interactions between bacteria and phages and then discuss how such a priori knowledge may help inform the study of AC when scaling up to in vivo models

12:00 - 12:30 Philipp Engel - University of Lausanne.

Honey bee gut microbiota – a versatile model for microbial symbiosis Specialized bacterial communities colonize the animal gut and impact health and disease of the host in manifold ways. However, their complex composition presents a veritable challenge for elucidating fundamental aspects of gut microbiota functions, ecology, and evolution. In my lab, we study the honey bee gut microbiota, a surprisingly simple, yet conserved gut community that is experimentally amenable and shares striking parallels to the mammalian system. Our overall goal is to combine experimental and genomic approaches to systematically understand functioning and evolution of this specialized, host-associated community.

In my talk, I will summarize two recent projects, in which we applied metabolomics and shotgun metagenomics, respectively, to disentangle metabolic capacities of individual community members and identify the community’s population genomic structure. Our results show distinct roles of bee gut symbionts in the conversion of major pollen wall constituents, but also suggest potential cross-feeding activities between them. Moreover, the genome-level information obtained from shotgun metagenomic data revealed the existence of discrete evolutionary lineages within previously defined species (as defined per 16S community profiling). These lineages are characterized by a remarkably high level of divergence and functional gene content variation suggesting diversification by adaptation to different metabolic niches.

- Session 3 -

14:00 - 14:30 Jan-Ulrich Kreft - University of Birmingham.

Persistence of Resistance: (co)existence of plasmids going complex.

Sonia Martins, Robert J Clegg, Qian Zhang, Akvile Zemgulyte, Chris M Thomas, Helen Wilson, Roberto de la Cruz, David Graham, Barth F Smets, Jan-Ulrich Kreft

Plasmids facilitate the propagation of resistance genes and antibiotic treatment selects for increased prevalence of these mobile genetic elements. However, plasmid prevalence often does not decrease when they are no longer selected for. To address this puzzle, I will briefly discuss the existence conditions of plasmids from the classic Stewart & Levin (1977) paper to more recent work on the so-called plasmid paradox, leading on to our work on the effect of the usually neglected host range of plasmids.

Plasmids with a narrow host range (NHR) and a broad host-range (BHR) co-exist in nature, suggesting both have fitness advantages and disadvantages. Since a broader host-range makes it more likely that the plasmid has not yet adapted to a particular host or vice versa, it is to be expected that broad host-range plasmids impose a greater fitness cost on the host. Given this disadvantage, what are the advantages of having a broad host-range? We developed an individual-based mathematical model to explore the dynamics of BHR and NHR plasmids in well-mixed chemostats and spatially structured biofilms and a mass-action model for chemostats for comparison. The NHR plasmid is assumed to infect only one of two species, while the BHR plasmid can infect both otherwise identical host species. We found that a costly NHR plasmid cannot persist in a chemostat unless it is helped by a costlier BHR plasmid that can infect the competing species. The NHR plasmid had to be incompatible to persist in a chemostat. Higher transfer rates of the BHR generated oscillations in abundance leading to bottlenecks with a chance of extinction of both plasmids in the stochastic individual-based model. In biofilms, having a broad host-range was particularly advantageous. However, incompatibility and lower transfer proficiency reduced the advantage of BHR. Overall, broad host range was the better strategy in both biofilms and chemostats. The results suggest that the coexistence of BHR and NHR plasmids can be explained by a trade-off between fitness cost, favoring vertical transmission of NHR plasmids, and broad host-range, favoring horizontal transmission, especially in spatially structured communities. Further, incompatibility may have evolved as a defense mechanism increasing the fitness of narrow host-range plasmids.

In addition to this 2 plasmids 2 hosts model about host range, I will present some results from a 1 plasmid in a more complex environment model – the activated sludge stage of a wastewater treatment plant where plasmids are continuously entering the system with the sewage, hosted by Enteric bacteria, and the residence time of bacteria exceeds the residence time of the solutes. I will show the effects of non-hosts, selection by an antimicrobial, transfer to the indigenous activated sludge bacteria and boost of transfer rate in transconjugants versus donors.

14:30 - 15:00 Kiran Patil - EMBL.

Uncovering metabolic and drug interaction landscape of the human gut microbiome.

The composition of the human gut microbiota is closely connected with both health and disease. It is influenced by several host factors including the immune system and life style, as well as by metabolic cross-feeding among different bacterial species. Furthermore, recent studies suggest that human targeted drugs can also influence the microbiome composition and the microbial community can in turn affect the drug availability and efficacy. Yet, the inter-species and drug-bacteria interactions remain largely unknown. I will present the results from a large collaborative project at EMBL-Heidelberg aimed at systematic characterization of inter-species and drug-bacteria interactions. Our results chart the hitherto unknown metabolic and xenobiotic interaction landscape of the gut microbiome and have implications for targeted microbiome modulation, drug design and personalized medicine.

15:00 - 15:30 Orkun Soyer - University of Warwick.

Understanding/engineering cell and community metabolism

The vision of synthetic biology to engineer biology using predictive models and high-throughput approaches. While this vision statement is very broad, synthetic biology efforts to date mostly focus on genetic circuit design in model organisms. I will present a different approach, where we combine engineering and natural principles towards creating multi-species microbial ecosystems. These so-called synthetic microbial communities can allow harvesting the full functional potential of the microbial world, leading to novel applications such as artificial gut, synthetic soil, waste-to-value conversion, and ecosystem functions in space missions. They can also act as model systems for understanding microbial interactions and ecology.
To successfully design synthetic microbial communities composed of multiple microbial species that are biochemically and industrially relevant, we first need to establish the design principles governing microbial interactions and develop the experimental tools for their characterisation and manipulation. Here, I will describe our ongoing efforts in discovering the reasons for metabolic interactions among microbes. I will argue that these metabolic interactions can be understood as an emergent property of the biochemical environment and associated thermodynamics within a multi-species system. Particularly, results from our recent research has shown that the thermodynamic basis of microbial growth can lead to co-existence, even under conditions that are kinetically predicted to lead to competition-driven exclusion. This thermodynamic inhibition can have significant consequences for the engineering of multi-species system.
I will illustrate these points in the context of experimental systems that we are developing in our group, where we aim to establish key metabolic interaction motifs among biochemically and biotechnologically relevant microbes and extending to inter-kingdom interactions with fungi and plants.

- Session 4 -

15:50 - 16:20 Alain Filloux - Imperial College London.

The type VI secretion system: an antibacterial nano-weapon

Bacterial pathogens are facing fierce conditions to colonize their host and launch successful infections. Not only they have to escape the immune system but they should also compete with other invading organisms or resident bacterial flora. This warfare is crucial for winning access to sometime scarce resources and pathogens employ a variety of strategies and molecular tools which make them successful.

Here we will discuss example of how the ESKAPE pathogen Pseudomonas aeruginosa eliminates other competitors by using a bacterial weapon called the type VI secretion system (T6SS). There are multi examples of bacterial toxins which are transported by the T6SS and injected into prey cells, including peptidoglycan hydrolases, phospholipases or DNases. These T6SS toxins are usually co-produced with an immunity to avoid self-intoxication. The transport of the toxins involves the T6SS nanomachine which is made of 13 core components and 3 sub-complexes called the membrane complex, the baseplate and the tail. The latter is made of a contractile sheath that surrounds a hollow tube consisting of a pile of hexameric Hcp. On tip of the Hcp tube sits a VgrG trimer, whose torch-like structure is sharpened by a PAAR protein put on top. The different toxins are accommodated within the Hcp hollow tube or at the tip of the tail by interacting either with VgrG or PAAR, using or not adaptor proteins. Upon sheath contraction Hcp/VgrG/PAAR and the cocktail of T6SS toxins are all expelled at once from the producing cell and injected into the prey cells resulting in intoxication.

We will discuss key aspects in the assembly of the T6SS nanomachine and review the kind of T6SS toxins that are injected into bacterial preys. We will also address how the characterization of novel T6SS toxins can be conducted and how these new toxins may point at the identification of new antimicrobial targets which could be used for drug development. This type of development is desperately needed in a context where bacteria have developed a range of ways to overcome ancient drugs and become recalcitrant to most available and sometime last-resort antibacterial.

16:20 - 16:50 Kendra Rumbaugh - Texas Tech University.

Microbial interactions in wound infections

Soft tissue infections, including burns, diabetic chronic wounds, abscesses and necrotizing fasciitis are a major source of morbidity and mortality worldwide and exert a tremendous economic burden. These infections are typically comprised of polymicrobial, biofilm-associated communities, which are exceedingly tolerant to treatment and often result in amputation. Although polymicrobial interactions contribute to antibiotic susceptibility, virulence and persistence, most studies still only focus on mono-infections. We have developed in vitro and in vivo models of polymicrobial wound infection to study how these factors affect the course of infection. Combined with powerful genetic tools we can now characterize bacterial gene expression and fitness determinants in vivo and provide important insight into a class of infection that is rapidly increasing, difficult to diagnose and treat, and potentially fatal.

16:50 - 17:20 Meera Unnikrishnan - University of Warwick.

Probing interactions at the gut microbial interface

Gut infections by pathogenic bacteria involve complex interactions with the native gut microbiota and with the host gut epithelium. We study the human gut pathogen Clostridium difficile, which is one of the major causes of hospital-acquired diarrhoea. C. difficile interactions with the gut microbiota and the colonic mucosa are critical for C. difficile colonisation. C. difficile biofilms influence colonisation and may play a role in persistent infections. I will discuss our recent studies on C. difficile mixed biofilms and new models to study C. difficile gut colonisation. We show that the LuxS quorum sensing system has a role in C. difficile biofilm formation. LuxS also modulates interactions with other gut bacteria within mixed biofilms. To study C. difficile interactions with the intestinal epithelium and with commensals in the anaerobic gut environment, we have developed a dual environment in vitro 3D human gut model. We have tracked C. difficile infection of the gut epithelium in this model and demonstrated inhibitory effects of gut commensal bacteria on C. difficile.


Posters


Adam Blanchard - University of Nottingham

Ovine footrot is a highly prevalent bacterial disease caused by Dichelobacter nodosus and characterised by the separation of the hoof horn from the underlying skin. The role of innate immune molecules and other bacterial communities in the development of footrot lesions remains unclear. This study shows a transcriptional differences between healthy and affected feet associated with wound healing and the inflammatory response. Investigation of the microbial population identified distinct bacterial populations in the different disease stages with Treponema, Mycoplasma, Bacillus and Porphyromonas being the most abundant This demonstrates for the first time there is a distinct microbial community associated with footrot and the host response.

Jing Chen - University of Warwick

The performance of microbial communities is subject to the available electron donor and acceptor in ambient environments. In the present work, we constructed synthetic microbial communities using two representative methanogens (Methanococcus maripaludis and Methanosarcina barkeri) and one sulphate reducer (Desulfovibrio vulgaris) to study their syntrophic interactions. In a defined chemical medium, methanogens relied on the production of hydrogen and acetate from lactate by D.vulgaris to grow and yield methane. We showed that with increasedsulphate levels, as the thermodynamically most favored electron acceptor, constructed communities stopped producing methane because D.vulgaris switched its metabolic pathway for a higher energy gain by reducingsulphate instead of the proton. Co-cultures with D.vulgaris and a hydrogenotrophic methanogen (M.maripaludis) were more resistant to thesulphate perturbation than with amixtroph (M.barkeri). Analysing this result of M.barkeri monocultures, we found that their methane productions were affected by ambient hydrogen pressure. Mass balance analysis of possible methane producing pathways of M.barkeri in sulphate-free co-cultures with D.vulgaris showed that the majority of M.barkeri population shifted to produce methane by using both acetate and hydrogen from D.vulgaris, and left more acetate in the cultures after sub-culturing event, following higher energy gain per mole acetate to methane reaction with external H2. These results indicate a key role for hydrogen in methanogenic syntheticcommunities, and provide evidence that the availability of thermodynamically favoured electron terminals inambient environment significantly governs the structure ofmicrobial community and their ability for methane production.

Emily Dixon- University of Birmingham

Candida albicans and Pseudomonas aeruginosa are commonly co-isolated from a variety of disease niches, including within the cystic fibrosis lung and upon indwelling medical devices. Their interactions have primarily been described as antagonistic and complex, including quorum sensing cross-talk, killing through phenazines, and competition for nutrients. Here, we identify an interaction in which P. aeruginosa induces aggregation of C. albicans in planktonic co-culture. C. albicans aggregation was induced within two hours of co-culture, and was observed with both lab and clinical strains of P. aeruginosa. Intriguingly, some, but not all, strains of P. aeruginosa also strongly induced the morphological switch of C. albicans, promoting hyphal formation. However, filamentation of C. albicans was not a prerequisite for aggregation, as aggregation levels were similar during co-culture with P. aeruginosa strains that did not promote hyphal formation. Using fluorescently labelled P. aeruginosa we confirmed that the bacteria are incorporated into the fungal aggregates. However, direct physical interactions between C. albicans and P. aeruginosa were not required for aggregate formation, as sterile culture supernatants induced similar levels of aggregation. Whilst other bacteria, such as staphylococci, are known to have a synergistic relationship with C. albicans, it was previously thought the P. aeruginosa inhibited C. albicans filamentation and biofilm formation. As biofilms are associated with persistence and enhanced protection from antimicrobials, this finding could help explain the persistence of heterogenous polymicrobial communities including both C. albicans and P. aeruginosa. It also highlights that this interaction is not solely antagonistic, but that dynamics could instead be strain and niche-specific. Future work will better characterise the causative molecule(s) and mechanism(s) and explore the effects of this interaction in vivo.

Alexia Hapeshi , Shannon C. Taggart, Anna Bruce and Nick R. Waterfield - University of Warwick

A stilbenoid antimicrobial with anti-biofilm effects on S. aureus biofilm.

Stilbenoids are natural products with important biological properties. Most are synthesised by plants in response to pathogenic attack. However, Photorhabdus and Bacillus bacteria engaged in symbioses with entomopathogenic nematodes also produce certain stilbene derivatives. Photorhabdus is an entomopathogenic bacterium, which produces a large set of toxins and digestive enzymes to kill and utilise the insect as a food source. Additionally, it releases multiple antimicrobial factors to eliminate competition in the insect carcass by other bacteria or fungi found in the soil. 3,5-dihydroxy-4-isopropylstilbene (IPS) is a small molecule produced by Photorhabdus, which has been shown to have antimicrobial, antifungal and anticancer activities and also seems to play an important role in symbiosis. In this study, we have investigated the antimicrobial effects of IPS against S. aureus and monitored the response of S. aureus to a sublethal concentration of IPS. We have also demonstrated that IPS not only has the ability to prevent biofilm formation but can also disrupt established S. aureus biofilms.

Jack Hassall- University of Warwick

Our intestines play home to over one thousand bacterial species, often referred to as the gut microbiota. This microbiota profoundly affects our bodies, providing an array of benefits. With disturbances to this community associated with pathogenic infection and diseases such as obesity, diabetes and inflammatory bowel disease. Production of an accurate in vitro model of the human gut alongside its microbiome would enhance pharmaceutical research, and allow for a complement to animal testing. Existing in vitro gut models focus on specific singular bacteria – human cell interactions, missing any community-based effect. Our aim is to engineer a synthetic microbiota, with an emphasis on tracking individual species. Introducing this representative community into our in vitro gut epithelial culture system will provide insights into pathogen infection strategies, and mechanisms by which the microbiota generates resistance. To date, we have acquired twelve gut species, and begun designs of a PMA (Propidium monoazide) – qPCR based tracking system. One major goal of the project is to test the inhibitory ability of our synthetic microbiota against Clostridium difficile infection. C. difficile is an opportunistic pathogen which targets the gut during times of depleted microbiota. Using classical quantification, we have been able to show that Bacteroides dorei in an in vitro gut model, is able to inhibit C. difficile growth over 24 hours. This inhibition, however, was unable to prevent or delay gut epithelial degradation.

Courtney Kousser, Callum Clark, Kerstin Voelz and Rebecca A. Hall- University of Birmingham

Pseudomonas aeruginosa inhibits Rhizopus microsporus germination via the sequestration of iron

Within the human body, microorganisms reside as part of a complex and varied ecosystem, where they rarely exist in isolation. Therefore, bacteria and fungi have co-evolved to develop elaborate and intricate relationships, utilising both physical and chemical communication mechanisms. Mucormycetes are spore-forming fungi belonging to the order Mucorales and are the causative agents of potentially fatal mucormycosis in immunocompromised individuals. Key to the pathogenesis of mucormycetes is the ability to swell and germinate leading to penetration of the surrounding tissues, angioinvasion, vessel thrombosis, and tissue necrosis. Mucormycete spores are found ubiquitously in the environment and in wounds, where they encounter a myriad of bacterial and fungal species including Pseudomonas aeruginosa. It is currently unknown whether mucormycetes participate in polymicrobial relationships, and if so, how this affects the pathogenesis, disease progression, and overall patient prognosis. This project aims to analyse the nature of the relationships between these fungal pathogens and the microorganisms they may encounter. Here we show that culture supernatants from P. aeruginosa and live bacteria are able to inhibit the germination of Rhizopus microsporus spores. This inhibition of germination was not due to the presence of quorum sensing molecules or toxins, but was instead due to iron restriction, as addition of exogenous iron restored germination. We hypothesise that P. aeruginosa secretes iron siderophores, which sequester the available iron, inhibiting fungal germination. Therefore, treatment of P. aeruginosa in trauma wounds could result in the release of this inhibition of germination, leaving the patient prone to an underlying fungal infection.

Beatriz Lagunas - University of Warwick

Development of sustainable agriculture approaches to increase plant productivity whilst minimising the impact on the environment is essential to achieve food security for an increasing human population. Nitrogen is the main limiting nutrient for plant production. Although it is one of the most abundant elements on earth, it is often unavailable to plants. As an evolutionary adaptive strategy, some plant species (such as legumes) have developed the ability to interact with specialised bacteria in a symbiotic relationship, overcoming the lack of nitrogen availability in soil. In this mutualistic partnership, the rhizobia fix nitrogen from the air and supply it to the plant in exchange for carbon and amino acid compounds. There are, however, variations on this process depending on the plant and bacterial individuals chosen for the study. Some plant species can be colonised by a range of rhizobial species resulting different outcomes depending on N2 fixation efficiency. As a first approach to investigate this plant-symbiont-soil complexity we are characterising the colonisation of the legume Medicago truncatula by three different rhizobial species (Sm1021, SmWSM1022 and SmWSM419). These different plant/rhizobia combinations vary in N2 fixation efficiency and we found that 419 and 1022 give rise to much larger plants compared to 1021, with also large differences in nodule number and nodule structure. To understand the interactions from a plant perspective we will use RNAseq to analyse a timeseries of early timepoints of rhizobial inoculation. To assess the soil contribution we are performing experiments with three different soil types that vary in texture, nitrogen and phosphate availability. To further understand the symbiont-soil relationship we are evaluating the influence of different rhizobial strain inoculation on soil microbiome composition, and vice versa, how the soil microbiome affects the outcome of plant-symbiont inoculation.

Iago Lopez - University of Warwick

Swarming bacteria were demonstrated to present a higher resistance to antibiotic with respect to another kind of motility. Nevertheless, the mechanisms that they use to protect themselves from the presence of antibiotic have not been elucidated yet. Here, we study the complex response of swarming bacteria when they invade a region containing a gradient of antibiotic which is the most common real-life scenario. We found that after three days of incubation, tolerant colonies which resist low concentrations of antibiotic start to emerge in regions where antibiotic is lower than the minimum inhibitory concentration. Afterwards, new non-tolerant colonies spread along the plate as the antibiotic diffuses.

Andrea Sofia Martinez Vernon - University of Warwick

The design of artificial ecosystems is a complex task. One of the considerations is the microorganisms needed to carry out the metabolic processes required in the ecosystem. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) contains extensive information regarding the relationship between organisms, genes and metabolic processes. However, these data are not easily accessible and there is an acute need for better tools that facilitate the integration of the KEGG databases to carry out analyses. To this end, we developed MetQy, an open source R package designed for query-based analysis of functional units in [meta]genomes and/or sets of genes using KEGG. The aim of MetQy is to enable a better understanding of metabolic capabilities of known genomes or user-specified [meta]genomes by using the available information. MetQy can help guide studies for the design of synthetic microbial communities and ecosystems.

Kim Summers - University of Birmingham

Antibiotic resistance is a serious threat to human health and new treatments for bacterial infections are urgently needed. The predatory bacterium, Bdellovibrio bacteriovorus (discovered in 1962) has been proposed as a potential alternative to antibiotics. We developed a mathematical predator prey model to predict the effects of Bdellovibrio on prey bacterial numbers. Our system is a simple chemostat, with an abiotic resource, a single prey species, exhibiting Monod kinetics and a predator species with a Holling type II functional response. As Bdellovibrio spends considerable time in a bdelloplast stage within a dead prey cell this species is also modelled, giving a delay between prey removal and birth of predators. We used the model to examine the effects of varying prey cell size on vulnerability to predation. We found larger cells are more easily predated, benefiting the predator. We also discovered an optimal attack rate for the predator. When varying substrate concentrations we observed a paradox of enrichment that is frequently seen in animal predator prey models, while varying predator attack rate demonstrated a tragedy of the commons via over exploitation of the prey resource. Our model shows the potential effectiveness of Bdellovibrio in combatting bacterial infections and highlights aspects of this system which needs more laboratory study.

Esther Sweeney & Freya Harrison - University of Warwick

The development of an ex vivo, porcine, lung model of cystic fibrosis to support mixed Pseudomonas aeruginosa and Staphylococcus aureus biofilm.

Chronic infections of the cystic fibrosis lung are poly-microbial. Robust laboratory models of multi-species biofilm infections are therefore needed to investigate bacterial interactions and the effects of antimicrobial treatment on a complex bacterial microbiota. Pseudomonas aeruginosa and Staphylococcus aureus are both dominant organisms associated with airway infections of cystic fibrosis patients and their interactions are considered important for the clinical outcome of disease. We have previously described an ex vivo pig lung model (EVPL) of cystic fibrosis that demonstrates the influence of host tissue interaction and biofilm structure on the growth and persistence of Pseudomonas aeruginosa lung infection. Here we show the progression of this model to support the growth of Staphylococcus aureus and the potential to establish mixed Pseudomonas aeruginosa and Staphylococcus aureus biofilm to further our understanding of inter-pathogen interactions in poly-microbial lung infections.