Biology subjects

Diggle, S. P.

Publications and source records attributed to Diggle, S. P..

15 recordsLinked to original sources

bioRxiv2026

Bacteriophage susceptibility varies within chronic Pseudomonas aeruginosa lung infections

Phage therapy is receiving renewed interest in the face of rising rates of antibiotic resistance. One drawback of phages as antibiotic agents is their high host specificity: phages can often only kill a subset of strains within a bacteria species. Phage specificity may be especially problematic for chronic infections, which tend to be genetically diverse, suggesting they may contain variation in phage susceptibility. Such within-population variation in phage susceptibility could make phage treatment less effective, however the extent of this variation in chronic bacterial infections has not been thoroughly studied. To address this gap, we investigated variation in phage susceptibility in four populations of Pa derived from chronic lung infections in people with cystic fibrosis. We first measured the lytic efficiency of 12 virulent phages across 40 isolates from each patient, which revealed substantial variation in susceptibility to four LPS-targeting phages in two of four lung-derived populations. Genomic analysis suggested that within-population variation in phage susceptibility was not explained by the acquisition or loss of phage defense systems, as phage defense system carriage did not strongly vary within lung-derived populations. Conversely, phylogenetic analysis of isolates from one lung-derived population revealed that some evolutionary transitions in phage susceptibility coincided with mutations in genes involved in LPS biosynthesis. This association suggested that within-patient diversification in cell-surface features may have been responsible for variation in phage susceptibility in this population. Finally, phenotypic characterization of lung-derived isolates revealed favorable clinical associations between phage susceptibility and antibiotic resistance in one population. However, associations were largely absent in other populations, suggesting the potential to use phages to drive favorable phenotypic shifts is limited in bacterial infections with existing variation in phage susceptibility. Collectively, this work shows that phage susceptibility can vary within Pa chronic infections in the lungs of people with cystic fibrosis, possibly as a consequence of standing variation in cell-surface features. This variation poses a challenge for phage therapy, necessitating new approaches to ensure high efficacy in the face of extreme within-patient heterogeneity.

evolutionary biology↗

bioRxiv2026

Pseudomonas aeruginosa Intra-Population Diversity Shapes Host Airway Epithelial Responses

In chronic pulmonary infection airways are colonized by genetically and phenotypically diverse Pseudomonas aeruginosa populations, yet almost everything known about P. aeruginosa pathogenesis has been learned from single clinical isolates or laboratory reference strains studied in isolation. Whether a diverse population behaves as the sum of its members remains unclear. We infected differentiated primary cystic fibrosis (CF) airway epithelial cells (CF-pAECs) at air-liquid interface with whole P. aeruginosa populations collected from the sputum of three adults with CF, and, in parallel, with genetic variants retrieved from the same populations. We found that host responses to whole populations were not predicted by responses to their derivative variants, and mixed populations did not exhibit the average expected response of the members. Variation in host response was dominated by the tissue-remodeling mediators vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), which differed distinctly between individual variants, whereas core pro-inflammatory cytokines (IL-6, IL-8, TNF-, IFN-{gamma}) varied comparatively little. Bacterial transcriptomes recorded during infection showed the same asymmetry. Clinical populations shared a transcriptional state distinct from PAO1, and mixed populations maintained stable expression of core regulatory, secretion, and DNA-repair loci (including hfq, xcpT, and ssb), while the derivative variants grown alone exhibited differential transcriptional profiles. Interactions among co-existing lineages therefore shape both bacterial physiology and host response, suggesting that the diverse population, not the single clone, is the appropriate unit of study in chronic infection.

microbiology↗

bioRxiv2026

Uncovering the multifaceted mechanism of action of a historical antimicrobial

Natural products have provided most of our modern pharmacopoeia, serving as active molecules or scaffolds for active molecules. Their use in drug development is often inspired by their traditional or historical medical use. For many decades, this discovery pipeline has focused on identifying a single molecule responsible for much of the biological activity of a raw natural product preparation (e.g. a whole-plant extract) and scoping this molecule for clinical potential. However, it is increasingly realised that historical/traditional remedies with significant biological activity may owe this activity to the combined action of multiple molecules. Concomitantly, microbiologists increasingly argue that effectively fighting antimicrobial-resistant infections will rely on combination therapies that combine multiple antimicrobials and/or adjuvant molecules. We previously reconstructed a complex historical remedy, Bald's eyesalve. Our reconstruction of this remedy had strong antibiofilm activity, which relied on the presence of multiple ingredients. Here, we report that Bald's eyesalve has multiple antibacterial effects on exemplar Gram-positive (Staphylococcus aureus) and Gram-negative (Acinetobacter baumannii) pathogens. Bald's eyesalve disrupts bacterial membrane integrity; inhibits expression of genes associated with bacterial adhesins, virulence factors and efflux pumps in both S. aureus and A. baumannii; inhibits quorum sensing in S. aureus; and causes downregulation of genes involved in de novo nucleotide biosynthesis in S. aureus. Lastly, we show that this multifaceted mechanism of action makes it difficult for S. aureus, A. baumannii, and Pseudomonas aeruginosa to evolve resistance against Bald's eyesalve. Bald's eyesalve could be used to identify a defined cocktail of natural products suitable for preclinical testing as a multi-target antibacterial preparation to which resistance may arise more slowly than current single-molecule antibiotics.

microbiology↗

bioRxiv2023

Unraveling Genomic Diversity in Pseudomonas aeruginosa Cystic Fibrosis Lung Infection and Its Impact on Antimicrobial Resistance

Pseudomonas aeruginosa is an opportunistic pathogen which causes chronic, drug-resistant lung infections in cystic fibrosis (CF) patients. In this study, we explore the role of genomic diversification and evolutionary trade-offs in antimicrobial resistance (AMR) diversity within P. aeruginosa populations sourced from CF lung infections. We analyzed 300 clinical isolates from four CF patients (75 per patient), and found that genomic diversity is not a consistent indicator of phenotypic AMR diversity. Remarkably, some genetically less diverse populations showed AMR diversity comparable to those with significantly more genetic variation. We also observed that hypermutator strains frequently exhibited increased sensitivity to antimicrobials, contradicting expectations from their treatment histories. Investigating potential evolutionary trade-offs, we found no substantial evidence of collateral sensitivity among aminoglycoside, beta-lactam, or fluoroquinolone antibiotics, nor did we observe trade-offs between AMR and growth in conditions mimicking CF sputum. Our findings suggest that (i) genomic diversity is not a prerequisite for phenotypic AMR diversity; (ii) hypermutator populations may develop increased antimicrobial sensitivity under selection pressure; (iii) collateral sensitivity is not a prominent feature in CF strains, and (iv) resistance to a single antibiotic does not necessarily lead to significant fitness costs. These insights challenge prevailing assumptions about AMR evolution in chronic infections, emphasizing the complexity of bacterial adaptation during infection. ImportanceUpon infection in the cystic fibrosis (CF) lung, Pseudomonas aeruginosa rapidly acquires genetic mutations, especially in genes involved in antimicrobial resistance (AMR), often resulting in diverse, treatment-resistant populations. However, the role of bacterial population diversity within the context of chronic infection is still poorly understood. In this study, we found that hypermutator strains of P. aeruginosa in the CF lung undergoing treatment with tobramycin evolved increased sensitivity to tobramycin relative to non-hypermutators within the same population. This finding suggests that antimicrobial treatment may only exert weak selection pressure on P. aeruginosa populations in the CF lung. We further found no evidence for collateral sensitivity in these clinical populations, suggesting that collateral sensitivity may not be a robust, naturally occurring phenomenon for this microbe. Preprint servers: This manuscript has been submitted as a preprint to bioRxiv

microbiology↗

bioRxiv2023

High prevalence of LPS mutants and R2-Pyocin susceptible variants in Pseudomonas aeruginosa populations sourced from cystic fibrosis lung infections

Chronic, highly antibiotic-resistant infections in cystic fibrosis (CF) lungs contribute to increasing morbidity and mortality. Pseudomonas aeruginosa, a common CF pathogen, exhibits resistance to multiple antibiotics, contributing to antimicrobial resistance (AMR). These bacterial populations display genetic and phenotypic diversity, but it is unclear how this diversity affects susceptibility to bacteriocins. R-pyocins, i.e. bacteriocins produced by P. aeruginosa, are phage tail-like antimicrobials. R-pyocins have potential as antimicrobials, however recent research suggests the diversity of P. aeruginosa variants within CF lung infections leads to varying susceptibility to R-pyocins. This variation may be linked to changes in lipopolysaccharide (LPS), acting as the R-pyocin receptor. Currently, it is unknown how frequently R-pyocin-susceptible strains are in chronic CF lung infection, particularly when considering the heterogeneity within these strains. In this study, we tested R2-pyocin susceptibility of 139 P. aeruginosa variants from 17 sputum samples of seven CF patients and analyzed LPS phenotypes. We found that 83% of sputum samples did not have R2-pyocin-resistant variants, while nearly all samples contained susceptible variants. there was no correlation between LPS phenotype and R2-pyocin susceptibility, though we estimate that about 76% of sputum-derived variants lack an O-specific antigen, 40% lack a common antigen, and 24% have altered LPS cores. The absence of a correlation between LPS phenotype and R-pyocin susceptibility suggests LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Our research supports the potential of R-pyocins as therapeutic agents, as many infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations. IMPORTANCECystic fibrosis (CF) patients often experience chronic, debilitating lung infections caused by antibiotic-resistant Pseudomonas aeruginosa, contributing to antimicrobial resistance (AMR). The genetic and phenotypic diversity of P. aeruginosa populations in CF lungs raises questions about their susceptibility to non-traditional antimicrobials, like bacteriocins. In this study, we focused on R-pyocins, a type of bacteriocin with high potency and a narrow killing spectrum. Our findings indicate that a large number of infectious CF variants are susceptible to R2-pyocins, even within diverse bacterial populations, supporting their potential use as therapeutic agents. The absence of a clear correlation between lipopolysaccharide (LPS) phenotypes and R-pyocin susceptibility suggests that LPS packing density may play a significant role in R-pyocin susceptibility among CF variants. Understanding the relationship between LPS phenotypes and R-pyocin susceptibility is crucial for developing effective treatments for these chronic infections.

microbiology↗

bioRxiv2021

Frequency of quorum sensing mutations in Pseudomonas aeruginosa strains isolated from different environments

Pseudomonas aeruginosa uses quorum sensing (QS) to coordinate the expression of multiple genes necessary for establishing and maintaining infection. It has previously been shown that lasR QS mutations frequently arise in cystic fibrosis (CF) lung infections, however, there has been far less emphasis on determining whether other QS system mutations arise during infection or in other environments. To test this, we utilized 852 publicly available sequenced P. aeruginosa genomes from the Pseudomonas International Consortium Database (IPCD) to study P. aeruginosa QS mutational signatures. To study isolates by source, we focused on a subset of 654 isolates collected from CF, wounds, and non-infection environmental isolates, where we could clearly identify their source. We also worked a small collection of isolates in vitro to determine the impact of lasR and pqs mutations on isolate phenotypes. We found that lasR mutations are common across all environments and are not specific to infection nor a particular infection type. We also found that the pqs system proteins PqsA, PqsH, PqsL and MexT, a protein of increasing importance to the QS field, are highly variable. Conversely, RsaL, a negative transcriptional regulator of the las system, was found to be highly conserved, suggesting selective pressure to repress las system activity. Overall, our findings suggest that QS mutations in P. aeruginosa are common and not limited to the las system; however, LasR is unique in the frequency of putative loss-of-function mutations.

microbiology↗

bioRxiv2021

Cell surface hydrophobicity determines Pseudomonas aeruginosa aggregate assembly

Bacteria live in spatially organized aggregates during chronic infections, where they adapt to the host environment, evade immune responses and resist therapeutic interventions. Although it is known that environmental factors such as polymers influence bacterial aggregation, it is not clear how bacterial adaptation during chronic infection impacts the formation and spatial organization of aggregates in the presence of polymers. Here we show that in an in vitro model of cystic fibrosis (CF) containing the polymers eDNA and mucin, O-specific antigen is a major factor in determining the formation of two distinct aggregate assembly types of Pseudomonas aeruginosa due to alterations in cell surface hydrophobicity. Our findings suggest that during chronic infection, interplay between cell surface properties and polymers in the environment may influence the formation and structure of bacterial aggregates, which would shed new light on the fitness costs and benefits of O-antigen production in environments such as CF lungs. ImportanceDuring chronic infection, several factors contribute to the biogeography of microbial communities. Heterogeneous populations of Pseudomonas aeruginosa form aggregates in cystic fibrosis airways, however, the impact of this population heterogeneity on spatial organization and aggregate assembly is not well understood. In this study we found that changes in O-specific antigen determine the spatial organization of P. aeruginosa cells by altering the relative cell surface hydrophobicity. This finding suggests a role for O-antigen in regulating P. aeruginosa aggregate size and shape in cystic fibrosis airways.

microbiology↗

bioRxiv2020

Heterogenous response to R-pyocin killing in populations of Pseudomonas aeruginosa sourced from cystic fibrosis lungs

Bacteriocins are proteinaceous antimicrobials produced by bacteria which are active against other strains of the same species. R-type pyocins are phage tail-like bacteriocins produced by Pseudomonas aeruginosa. Due to their anti-pseudomonal activity, R-pyocins have potential as therapeutics in infection. P. aeruginosa is a Gram-negative opportunistic pathogen and is particularly problematic for individuals with cystic fibrosis (CF). P. aeruginosa from CF lung infections develop increasing resistance to antibiotics, making new treatment approaches essential. P. aeruginosa populations become phenotypically and genotypically diverse during infection, however, little is known of the efficacy of R-pyocins against heterogeneous populations. R-pyocins vary by subtype (R1-R5), distinguished by binding to different residues on the lipopolysaccharide (LPS). Each type varies in killing spectrum, and each strain produces only one R-type. To evaluate the prevalence of different R-types, we screened P. aeruginosa strains from the International Pseudomonas Consortium Database (IPCD) and from our biobank of CF strains. We found that (i) R1-types were the most prevalent R-type among strains from respiratory sources; (ii) there is a large number of strains lacking R-pyocin genes, and (iii) isolates collected from the same patient have the same R-type. We then assessed the impact of intra-strain diversity on R-pyocin susceptibility and found a heterogenous response to R-pyocins within populations, likely due to differences in the LPS core. Our work reveals that heterogeneous populations of microbes exhibit variable susceptibility to R-pyocins and highlights that there is likely heterogeneity in response to other types of LPS-binding antimicrobials, including phage. ImportanceR-pyocins have potential as alternative therapeutics against Pseudomonas aeruginosa in chronic infection, however little is known about the efficacy of R-pyocins in heterogeneous bacterial populations. P. aeruginosa is known to become resistant to multiple antibiotics, as well as evolve phenotypic and genotypic diversity over time; thus it is particularly difficult to eradicate in chronic cystic fibrosis (CF) lung infections. In this study, we found that P. aeruginosa populations from CF lungs maintain the same R-pyocin genotype but exhibit heterogeneity in susceptibility to R-pyocins from other strains. Our findings suggest there is likely heterogeneity in response to other types of LPS-binding antimicrobials, such as phage, highlighting the necessity of further studying the potential of LPS-binding antimicrobial particles as alternative therapies in chronic infections.

microbiology↗

bioRxiv2020

The evolution of virulence in Pseudomonas aeruginosa during chronic wound infection

Opportunistic pathogens are associated with a number of chronic human infections, yet the evolution of virulence in these organisms during chronic infection remains poorly understood. Here, we tested the evolution of virulence in the human opportunistic pathogen Pseudomonas aeruginosa in a murine chronic wound model using a two-part serial passage and sepsis experiment, and found that virulence evolved in different directions in each line of evolution. We also assessed P. aeruginosa adaptation to a chronic wound after 42 days of evolution, and found that morphological diversity in our evolved populations was limited compared to that previously described in cystic fibrosis (CF) infections. Using whole genome sequencing, we found that genes previously implicated in P. aeruginosa pathogenesis (lasR, pilR, fleQ, rpoN, and pvcA), acquired mutations during the course of evolution in wounds, with some mutations evolving in parallel across all lines of evolution. Our findings highlight that (i) P. aeruginosa heterogeneity may be less extensive in chronic wounds than in CF lungs; (ii) genes involved in P. aeruginosa pathogenesis acquire mutations during chronic wound infection; (iii) similar genetic adaptations are employed by P. aeruginosa across multiple infection environments, and (iv) current models of virulence may not adequately explain the diverging evolutionary trajectories observed in an opportunistic pathogen during chronic wound infection.

microbiology↗

bioRxiv2019

Allelic polymorphism shapes collective phenotypes in evolving Pseudomonas aeruginosa populations

Pseudomonas aeruginosa is an opportunistic pathogen that chronically infects the lungs of individuals with cystic fibrosis (CF) by forming antibiotic resistant biofilms. Emergence of phenotypically diverse isolates within CF P. aeruginosa populations has previously been reported, however, the impact of heterogeneity on social behaviors and community function is poorly understood. Here we describe how this heterogeneity impacts on behavioral traits by evolving the strain PAO1 in biofilms grown in a synthetic sputum medium for 50 days. We measured social trait production and antibiotic tolerance and used a metagenomic approach to analyze and assess genomic changes over the duration of the evolution experiment. We found that (i) evolutionary trajectories were reproducible in independently evolving populations; (ii) over 60% of genomic diversity occurred within the first 10 days of selection. We then focused on quorum sensing (QS), a well-studied P. aeruginosa trait that is commonly mutated in strains isolated from CF lungs. We found that at the population level (i) evolution in sputum medium selected for decreased production of QS and QS-dependent traits; (ii) there was a significant correlation between lasR mutant frequency, the loss of protease and the 3O-C12-HSL signal, and an increase in resistance to clinically relevant {beta}-lactam antibiotics, despite no previous antibiotic exposure. Overall, our findings provide insights into the effect of allelic polymorphism on community functions in diverse P. aeruginosa populations. Further, we demonstrate that P. aeruginosa population and evolutionary dynamics can impact on traits important for virulence and can lead to increased tolerance to {beta}-lactam antibiotics.

microbiology↗

bioRxiv2018

Combinatorial quorum sensing in Pseudomonas aeruginosa allows for novel cheating strategies

In the opportunistic pathogen Pseudomonas aeruginosa, quorum sensing (QS) is a social trait that is exploitable by non-cooperating cheats. Previously it has been shown that by linking QS to the production of both public and private goods, cheats can be prevented from invading populations of cooperators and this has been termed a metabolic incentive to cooperate. We hypothesized P. aeruginosa could evolve novel cheating strategies to circumvent private goods metabolism by rewiring its combinatorial response to two QS signals (3O-C12-HSL and C4-HSL). We performed a selection experiment that cycled P. aeruginosa between public and private goods growth media and evolved an isolate which rewired its control of cooperative protease expression from a synergistic (AND-gate) response to dual signal input, to a 3O-C12-HSL only response. We show that this isolate circumvents metabolic incentives to cooperate and acts as a combinatorial signaling cheat, with a higher fitness in competition with its ancestor. Our results show three important principles; first, combinatorial QS allows for diverse social strategies to emerge; second, that restrictions levied by private goods are not sufficient to explain the maintenance of cooperation in natural populations and third that modifying combinatorial QS responses could result in important physiological outcomes in bacterial populations.

microbiology↗

bioRxiv2018

Competition in biofilms between Pseudomonas aeruginosa cystic fibrosis isolates is driven by R-pyocins

Pseudomonas aeruginosa is an opportunistic pathogen responsible for a number of different human infections and is the leading cause of morbidity and mortality in cystic fibrosis (CF) patients. P. aeruginosa infections are difficult to treat due to a number of antibiotic resistance mechanisms and the organisms propensity to form multicellular biofilms. Epidemic strains of P. aeruginosa often dominate within the lungs of individual CF patients, but how they achieve this is poorly understood. One of the ways strains of P. aeruginosa can compete, is by producing chromosomally encoded bacteriocins, called pyocins. Three major classes of pyocin have been identified in P. aeruginosa: soluble pyocins (S-types) and tailocins (R- and F-types). In this study, we investigated the distribution of S- and R-type pyocins in 24 clinical strains isolated from individual CF patients and then focused on understanding their roles on inter-strain competition. We found that (i) each strain produced only one R-pyocin type, but the number of S-pyocins varied between strains; (ii) R-pyocins were generally important for strain dominance during competition assays in planktonic cultures and biofilm communities in strains with both disparate R and S pyocin sub-types. (iii) purified R-pyocins demonstrated significant antimicrobial activity against established biofilms. Our work provides support for a key role played by R-pyocins in the competition between P. aeruginosa strains, and may help explain why certain strains and lineages of P. aeruginosa dominate and displace others during CF lung infection. Furthermore, we demonstrate the potential of exploiting R-pyocins for therapeutic gains in an era when antibiotic resistance is a global concern.\n\nIMPORTANCEA major clinical problem caused by Pseudomonas aeruginosa, is chronic biofilm infection of the lungs in individuals with cystic fibrosis (CF). Epidemic P. aeruginosa strains dominate and displace others during CF infection, but these intra-species interactions remain poorly understood. Here we demonstrate that R-pyocins (bacterocins) are important factors in driving competitive interactions in biofilms between P. aeruginosa strains isolated from different CF patients. In addition, we found that these phage-like pyocins are inhibitory against mature biofilms of susceptible strains. This highlights the potential of R-pyocins as antimicrobial and antibiofilm agents, at a time when new antimicrobial therapies are desperately needed.

microbiology↗

bioRxiv2017

A simple mung bean infection model for studying the virulence of Pseudomonas aeruginosa

Here we highlight the development of a simple and high throughput mung bean model to study virulence in the opportunistic pathogen Pseudomonas aeruginosa. The model is easy to setup and infection and virulence can be monitored for up to 10 days. In a first test of the model, we found that mung bean seedlings infected with PAO1 showed poor development of roots and high mortality rates compared to un-infected controls. We also found that a quorum sensing (QS) mutant was significantly less virulent when compared with the PAO1 wild type. Our work introduces a new tool for studying virulence in P. aeruginosa, that will allow for high throughput virulence studies of mutants, and for testing the in vivo efficacy of new therapies at a time when new antimicrobial drugs are desperately needed.

microbiology↗

bioRxiv2016

The social evolution of siderophore production in Pseudomonas aeruginosa is environmentally determined.

Bacteria secrete various exoproducts whose benefits can be shared by all cells in the vicinity. The potential importance of these \"public goods\" in bacterial evolutionary ecology has been extensively studied. Cheating by siderophore-null mutants of the opportunistic pathogen Pseudomonas aeruginosa has received particular attention. The potential of siderophore mutants to attenuate virulence, and the possibility of exploiting this for clinical ends, have generated a wealth of publications. However, the possibility that genotype {middle dot} environment interactions govern the evolutionary consequences of siderophore loss has been almost entirely ignored. A review of the available literature revealed (i) widespread use of an undefined mutant as a siderophore cheat; and (ii) a reliance on experiments conducted in iron-limited minimal medium. Whole genome sequencing of the undefined mutant revealed a range of mutations affecting phenotypes other than siderophore production. We then conducted cheating assays using defined deletion mutants, grown in conditions designed to model infected fluids and tissue in CF lung infection and non-healing wounds. Depending on the environment, we found that siderophore loss could lead to cheating, simple fitness defects, or no fitness effect at all. It is therefore crucial to develop appropriate in vitro growth conditions in order to better predict the social evolution of traits in vivo.

microbiology↗

bioRxiv2016

The fitness of Pseudomonas aeruginosa quorum sensing signal cheats is influenced by the diffusivity of the environment

Experiments examining the social dynamics of bacterial quorum sensing (QS) have focused on mutants which do not respond to signals, and the role of QS-regulated exoproducts as public goods. The potential for QS signal molecules to themselves be social public goods has received much less attention. Here, we analyse how signal-deficient (lasI-) mutants of the opportunistic pathogen Pseudomonas aeruginosa interact with wild-type cells in an environment where QS is required for growth. We show that when growth requires a private intracellular metabolic mechanism activated by the presence of QS signal, lasI- mutants act as social cheats and outcompete signal-producing wild-type bacteria in mixed cultures, because they can use the signals produced by wild type cells. However, reducing the ability of signal molecules to diffuse through the growth medium, results in signal molecules becoming less accessible to mutants, leading to reduced cheating. Our results indicate that QS signal molecules can be considered as social public goods in a way that has been previously described for other exoproducts, but that spatial structuring of populations reduces exploitation by non-cooperative signal cheats.\n\nImportanceBacteria communicate via signaling molecules to regulate the expression of a whole range of genes. This process, termed quorum sensing (QS), moderates bacterial metabolism in many environmental conditions, from soil and water (where QS-regulated genes influence nutrient cycling) to animal hosts (where QS-regulated genes determine pathogen virulence). Understanding the ecology of QS could therefore yield vital clues as to how we might modify bacterial behaviour for environmental or clinical gains. Here, we demonstrate that QS signals act as shareable public goods. This means that their evolution, and therefore population-level responses to interference with QS, will be constrained by population structure. Further, we show that environmental structure (constraints on signal diffusion) alters the accessibility of QS signals and demonstrates that we need to consider population and environmental structure to help us further our understanding of QS signaling systems.

microbiology↗