Biology subjects

Nadell, C.

Publications and source records attributed to Nadell, C..

6 recordsLinked to original sources

bioRxiv2026

Biofilm compactness and spatial community composition determine bacterial phage-susceptibility

Bacteriophages (phages) are viruses that infect bacteria, often posing a threat to their survival. In recent years, research has shifted from studying bacteria-phage interactions in homogeneous, well-mixed environments to investigating more complex heterogeneous, structured communities, thereby more accurately reflecting bacterial life in natural and disease-associated settings. So far, these studies predominantly tested interactions of phages and single-species biofilms, despite the dominance of highly diverse biofilm communities in nature. Here, we investigated how different lytic phages spread in and infect a synthetic community composed of Escherichia coli, Kluyvera cryocrescens, and Vibrio anguillarum. We found that E. coli was protected from eradication by the T7-coliphage when embedded in a multispecies biofilm and covered by the two other species, where the V. anguillarum biofilm matrix was essential for protection of E. coli. The protective nature of the V. anguillarum matrix also ensured survival of K. cryocrescens exposed to the lytic kluyveraphage Lyn. V. anguillarum mutants lacking the matrix synthesis genes vpsMNOP or rbmC failed to protect E. coli despite forming biofilms. Labelling of phages indicated that these were not trapped in the matrix of the wildtype. Instead, advanced image analysis revealed that the mutants displayed biofilms with lower cell density, resulting in the E. coli clusters being less tightly surrounded by V. anguillarum cells, which opened gaps for phage entry. These findings highlight that community context and matrix composition play a major role in phage-bacteria dynamics.

microbiology↗

bioRxiv2024

Bacterial quorum sensing controls carbon metabolism to optimize growth in changing environmental conditions.

Bacteria sense population density via the cell-cell communication system called quorum sensing (QS). Some QS-regulated phenotypes (e.g., secreted enzymes, chelators), are public goods exploitable by cells that stop producing them. We uncovered a phenomenon in which Vibrio cells optimize expression of the methionine and tetrahydrofolate (THF) synthesis genes via QS. Strains that are genetically locked at high cell density grow slowly in minimal glucose media and suppressor mutants accumulate via inactivating-mutations in metF (methylenetetrahydrofolate reductase) and luxR (the master QS transcriptional regulator). Methionine/THF synthesis genes are repressed at low cell density when glucose is plentiful and are de-repressed by LuxR at high cell density as glucose becomes limiting. In mixed cultures, QS mutant strains initially co-exist with wild-type, but as glucose is depleted, wild-type outcompetes the QS mutants. Thus, QS regulation of methionine/THF synthesis is a fitness benefit that links private and public goods within the QS regulon, preventing accumulation of QS-defective mutants.

microbiology↗

bioRxiv2023

Spatial propagation of temperate phages within and among biofilms

Bacteria form groups comprised of cells and a secreted polymeric matrix that controls their spatial organization. These groups - termed biofilms - can act as refuges from environmental disturbances and from biotic threats, including phages. Despite the ubiquity of temperate phages and bacterial biofilms, live propagation of temperate phages within biofilms has never been characterized on cellular spatial scales. Here, we leverage several approaches to track temperate phages and distinguish between lytic and lysogenic host infections. We determine that lysogeny within E. coli biofilms initially occurs within a predictable region of cell group packing architecture on the biofilm periphery. Because lysogens are generally found on the periphery of large cell groups, where lytic viral infections also reduce local biofilm cell packing density, lysogens are predisposed to disperse into the passing liquid and are over-represented in biofilms formed from the dispersal pool of the original biofilm-phage system. Comparing our results with those for virulent phages reveals that temperate phages have previously unknown advantages in propagating over long spatial and time scales within and among bacterial biofilms.

microbiology↗

bioRxiv2023

Dispersal of a dominant competitor can drive multispecies coexistence in biofilms

Despite competition for both space and nutrients, bacterial species often coexist within structured, surface-attached communities termed biofilms. While these communities play important, widespread roles in ecosystems and are agents of human infection, understanding how multiple bacterial species assemble to form these communities and what physical processes underpin the composition of multispecies biofilms remains an active area of research. Using a model three-species community composed of P. aeruginosa, E. coli, and E. faecalis, we show with cellular scale resolution that biased dispersal of the dominant community member, P. aeruginosa, prevents competitive exclusion from occurring, leading to coexistence of the three species. A P. aeruginosa bqsS deletion mutant no longer undergoes periodic mass dispersal, leading to local competitive exclusion of E. coli. Introducing periodic, asymmetric dispersal behavior into minimal models parameterized by only maximal growth rate and local density supports the intuition that biased dispersal of an otherwise dominant competitor can permit coexistence generally. Colonization experiments show that WT P. aeruginosa is superior at colonizing new areas in comparison to{Delta} bqsS P. aeruginosa, but at the cost of decreased local competitive ability against E. coli and E. faecalis. Overall, our experiments document how one species modulation of a competition-dispersal-colonization trade-off can go on to influence the stability of multispecies coexistence in spatially structured ecosystems.

microbiology↗

bioRxiv2020

Matrix-trapped viruses can protect bacterial biofilms from invasion by colonizing cells

Bacteria often live in the context of spatially restricted groups held together by a self-secreted, adhesive extracellular matrix. These groups, termed biofilms, are likely where many phage-bacteria encounters occur. A number of recent studies have documented that phages can be trapped in the outer matrix layers of biofilms, such that the bacteria inside are protected from exposure. It is not known, however, what might happen after this: are the trapped phages still viable on the biofilm exterior? If so, do they pose a threat to newly arriving cells that might otherwise colonize the existing biofilm? Here we set out to address these questions using a biofilm-producing strain of Escherichia coli and its lytic phage T7. Prior work has demonstrated that T7 phages are trapped in the outermost layers of curli polymers within the E. coli matrix. We show that these phages do remain viable and kill incoming colonizing cells so long as they are T7-susceptible. If colonizing cells arrive to the outside of a resident biofilm before phages do, they can still be killed by phage exposure if it occurs soon thereafter. However, if colonizing cells are present on the biofilm long enough before phage exposure, they gain phage protection via envelopment within curli-producing clusters of the resident biofilm cells. This work establishes that phages trapped in the outer matrix layers of a resident biofilm can be incidentally weaponized as a mode of protection from competition by newly arriving cells that might otherwise colonize the biofilm exterior.

microbiology↗

bioRxiv2016

Theory for the spatiotemporal interaction between lytic phages and biofilm-dwelling bacteria

Many bacteria are adapted for attaching to surfaces and for building complex communities, termed biofilms. The biofilm mode of life is predominant in bacterial ecology. So, too, is exposure of bacteria to ubiquitous viral pathogens, termed bacteriophages. Although biofilmphage encounters are likely to be very common in nature, little is known about how phages might interact with biofilm-dwelling bacteria. It is also unclear how the ecological dynamics of phages and their hosts depend on the biological and physical properties of the biofilm environment. To make headway in this area, here we develop the first biofilm simulation framework that captures key mechanistic features of biofilm growth and phage infection. Using these simulations, we find that the equilibrium state of interaction between biofilms and phages is governed largely by nutrient availability to biofilms, infection likelihood per host encounter, and the ability of phages to diffuse through biofilm populations. Interactions between the biofilm matrix and phage particles are thus likely to be of fundamental importance, controlling the extent to which bacteria and phages can coexist in natural contexts. Our results open avenues to new questions of host-parasite coevolution and horizontal gene transfer in spatially structured biofilm contexts.

microbiology↗