Host control of the microbiome: Mechanisms, evolution, and disease.

Many species, including humans, host communities of symbiotic microbes. There is a vast literature on the ways these microbiomes affect hosts, but here we argue for an increased focus on how hosts affect their microbiomes. Hosts exert control over their symbionts through diverse mechanisms, including immunity, barrier function, physiological homeostasis, and transit. These mechanisms enable hosts to shape the ecology and evolution of microbiomes and generate natural selection for microbial traits that benefit the host. Our microbiomes result from a perpetual tension between host control and symbiont evolution, and we can leverage the host's evolved abilities to regulate the microbiota to prevent and treat disease. The study of host control will be central to our ability to both understand and manipulate microbiotas for better health.

A Quantitative Review of Certified Burn Therapist's Involvement in the JBCR Publications and ABA Leadership.

The Burn Therapist Certification (BT-C) was introduced in 2018 to acknowledge occupational and physical therapists with specialized knowledge, skill, and experience in promotion of quality burn rehabilitation. Currently, BT-Cs make up 11.7% of therapists working in burn rehabilitation (n=39/333). The purpose of this review is to report on contributions of BT-Cs to organizational leadership of the American Burn Association (ABA) and in the generation of new knowledge through peer-reviewed publications. Despite the small percentage of burn therapists who are certified, they have a disproportionately large involvement in leadership within the ABA and burn research in the Journal of Burn Care and Rehabilitation (JBCR). From 2018-2023, BT-Cs have contributed to nearly one-half (n=26/56) of therapy authored publications in the JBCR and almost one-third (n=65/202) of accepted abstracts at the ABA annual meeting. Certified burn therapists demonstrate substantial involvement throughout the ABA including maintaining an 85% membership rate and on average serve in 53% (n=31/59) of the therapy allotted committee positions. Therapist pursuit of certification can have a profound impact on the burn community through publication, leadership, and development of care standards. Although therapists have indicated a desire to pursue certification, barriers related to a lack of association and center support have been identified. The burn community has endorsed certification as a mark of excellence for nurses and physicians. Maximizing the value of a transdisciplinary approach to burn care is also dependent on excellence from therapies. If the burn community desires improved engagement and contribution from therapies, it should support therapist certification.

Estrogenic Isoflavones in Clover Plants, Flower Nectar, Unripe Honeys and Mature Honeys: A Natural Biochemical Transformation of Isoflavones by Honeybees.

This study is the first to report on the presence of oestrogenic compounds in different clover flower nectar samples, in bee-deposited nectars collected from hive combs (unripe honey) and in mature honeys harvested from the same hives. The clover species investigated were two red clover (Trifolium pratense) cultivars, bred specifically for high isoflavone content, alongside a sainfoin (Onobrychis viciifolia) and a purple clover (T. purpureum) cultivar. A total of eight isoflavones, four of them non-glycosidic (biochanin A, formononetin, genistein and daidzein) the others glycosidic (sissotrin, ononin, genistin and daidzin), were targeted for identification and quantification in this study using high-performance thin-layer chromatography (HPTLC). Leaves and flower bracts of the clover samples were also investigated. Different isoflavone profiles were found across the four clover species and also in the different samples collected from each species indicating that, most likely due to the activity of honeybee (Apis mellifera) salivary enzymes, biochemical conversions take place when these bioactive compounds transition from flower nectar into ripe honey. Among the four investigated clover species, the two red clover cultivars, including their honeys, were found to contain higher levels of estrogenic compounds compared to other two cultivars.

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity.

BACKGROUND: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. RESULT: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. CONCLUSION: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.

Determination of Physicochemical Characteristics, Phytochemical Profile and Antioxidant Activity of Various Clover Honeys.

This paper reports on some physicochemical and phytochemical characteristics (i. e. pH, electrical conductivity, colour, moisture content, total phenolic content, sugar profile) and in vitro antioxidant activity of honeys harvested from five legume species, red clover (Trifolium pratense), balansa clover (T. michelianum), Persian clover (T. resupinatum), purple clover (T. purpureum) and sanfoin, also known as holy clover (Onobrychis viciifolia), that were grown in enclosed shade houses to ensure that the honeys' characteristics are reflective of a truly monofloral honey. Glucose and fructose, determined via High-Performance Thin-Layer Chromatography (HPTLC) analysis, were found as the main sugars in all investigated honeys with the ratio of fructose to glucose ranging from 1 : 1.2 to 1 : 1.6. The honeys' pH values ranged from 3.9 to 4.6 which met Codes Alimentarius (CA) requirements. The moisture content was found to be between 17.6 and 22.2 % which in some cases was slightly higher than CA requirements (≤20 %). The honeys' colour values, prior and after filtration, were between 825.5-1149.5 mAU and 532.4-824.8 mAU respectively, illustrating golden yellow to deep yellow hues. The total phenolic content (TPC) of the honeys was determined using a modified Folin-Ciocalteu assay. Their antioxidant activity was captured by the Ferric Reducing-Antioxidant Power (FRAP) assay as well as HPTLC analysis coupled with 2,2-diphenyl-1-picrylhydrazyl (DPPH) derivatisation. The highest total phenolic content was found in red clover honey (45.4 mg GAE/100 g) whereas purple clover honey showed the highest level of activity in the FRAP assay (7.3 mmol Fe2+/kg). HPTLC-DPPH analysis of the honeys' organic extracts demonstrated the presence of various bioactive compounds that contribute to their overall antioxidant activity. This study developed a methodology for producing monofloral clover honeys in a space limited, enclosed production system, which allowed to collate important baseline data for these honeys that can serve as the foundation for their potential future development into commercial honeys, including honeys that can be used for medicinal purposes.

Psychiatric Risk Factors and Burn Severity in Self-Immolation.

Self-immolation, a form of self-harm involving setting oneself on fire, is associated with high mortality, morbidity, and healthcare burden. This study aimed to characterize potential clinical correlates and predisposing factors for self-immolation based on burn severity using Total Body Surface Area (TBSA) percentage scoring. Additional objectives included identifying motivational elements, associated risk factors, and clinical characteristics to optimize patient care and reduce future self-immolation incidents. A retrospective review of admissions to the Arizona Burn Center from July 2015 to August 2022 identified 103 self-immolation patients for the study. Burn severity was categorized as mild to moderate (TBSA < 20%) or severe (TBSA ≥ 20%) based on TBSA. This study population had a mortality rate of 21%. Positive urine drug screens were found in 44% of subjects, and 63% having chronic substance use, with methamphetamine (37%) and alcohol (30%) being the most prevalent. Underlying psychiatric illnesses were present in 83% of patients. Suicidal intent strongly predicted severe burns (p < 0.001) among the 68 severe burn cases identified. In conclusion, this study emphasizes that the presence of suicidal intent among self-immolation patients significantly correlates with burn severity. These findings highlight the importance of involving psychiatric services early in patient care to improve outcomes and reduce the recurrence of self-immolation acts.

Maximizing wound coverage in full-thickness skin defects: A randomized-controlled trial of autologous skin cell suspension and widely meshed autograft versus standard autografting.

BACKGROUND: Traumatic insults, infection, and surgical procedures can leave skin defects that are not amenable to primary closure. Split-thickness skin grafting (STSG) is frequently used to achieve closure of these wounds. Although effective, STSG can be associated with donor site morbidity, compounding the burden of illness in patients undergoing soft tissue reconstruction procedures. With an expansion ratio of 1:80, autologous skin cell suspension (ASCS) has been demonstrated to significantly decrease donor skin requirements compared with traditional STSG in burn injuries. We hypothesized that the clinical performance of ASCS would be similar for soft tissue reconstruction of nonburn wounds. METHODS: A multicenter, within-patient, evaluator-blinded, randomized-controlled trial was conducted of 65 patients with acute, nonthermal, full-thickness skin defects requiring autografting. For each patient, two treatment areas were randomly assigned to concurrently receive a predefined standard-of-care meshed STSG (control) or ASCS + more widely meshed STSG (ASCS+STSG). Coprimary endpoints were noninferiority of ASCS+STSG for complete treatment area closure by Week 8, and superiority for relative reduction in donor skin area. RESULTS: At 8 weeks, complete closure was observed for 58% of control areas compared with 65% of ASCS+STSG areas (p = 0.005), establishing noninferiority of ASCS+STSG. On average, 27.4% less donor skin was required with ASCS+ STSG, establishing superiority over control (p < 0.001). Clinical healing (≥95% reepithelialization) was achieved in 87% and 85% of Control and ASCS+STSG areas, respectively, at 8 weeks. The treatment approaches had similar long-term scarring outcomes and safety profiles, with no unanticipated events and no serious ASCS device-related events. CONCLUSION: ASCS+STSG represents a clinically effective and safe solution to reduce the amount of skin required to achieve definitive closure of full-thickness defects without compromising healing, scarring, or safety outcomes. This can lead to reduced donor site morbidity and potentially decreased cost associated with patient care.Clincaltrials.gov identifier: NCT04091672. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level I.

Microbiome diversity protects against pathogens by nutrient blocking.

The human gut microbiome plays an important role in resisting colonization of the host by pathogens, but we lack the ability to predict which communities will be protective. We studied how human gut bacteria influence colonization of two major bacterial pathogens, both in vitro and in gnotobiotic mice. Whereas single species alone had negligible effects, colonization resistance greatly increased with community diversity. Moreover, this community-level resistance rested critically upon certain species being present. We explained these ecological patterns through the collective ability of resistant communities to consume nutrients that overlap with those used by the pathogen. Furthermore, we applied our findings to successfully predict communities that resist a novel target strain. Our work provides a reason why microbiome diversity is beneficial and suggests a route for the rational design of pathogen-resistant communities.

Reactivity of complex communities can be more important than stability.

Understanding stability-whether a community will eventually return to its original state after a perturbation-is a major focus in the study of various complex systems, particularly complex ecosystems. Here, we challenge this focus, showing that short-term dynamics can be a better predictor of outcomes for complex ecosystems. Using random matrix theory, we study how complex ecosystems behave immediately after small perturbations. Our analyses show that many communities are expected to be 'reactive', whereby some perturbations will be amplified initially and generate a response that is directly opposite to that predicted by typical stability measures. In particular, we find reactivity is prevalent for complex communities of mixed interactions and for structured communities, which are both expected to be common in nature. Finally, we show that reactivity can be a better predictor of extinction risk than stability, particularly when communities face frequent perturbations, as is increasingly common. Our results suggest that, alongside stability, reactivity is a fundamental measure for assessing ecosystem health.

The evolution of short- and long-range weapons for bacterial competition.

Bacteria possess a diverse range of mechanisms for inhibiting competitors, including bacteriocins, tailocins, type VI secretion systems and contact-dependent inhibition (CDI). Why bacteria have evolved such a wide array of weapon systems remains a mystery. Here we develop an agent-based model to compare short-range weapons that require cell-cell contact, with long-range weapons that rely on diffusion. Our model predicts that contact weapons are useful when an attacking strain is outnumbered, facilitating invasion and establishment. By contrast, ranged weapons tend to be effective only when attackers are abundant. We test our predictions with the opportunistic pathogen Pseudomonas aeruginosa, which naturally carries multiple weapons, including CDI and diffusing tailocins. As predicted, short-range CDI can function at low and high frequencies, while long-range tailocins require high frequency and cell density to function effectively. Head-to-head competition experiments with the two weapon types further support our predictions: a tailocin attacker defeats CDI only when it is numerically dominant, but then we find it can be devastating. Finally, we show that the two weapons work well together when one strain employs both. We conclude that short- and long-range weapons serve different functions and allow bacteria to fight both as individuals and as a group.

Chaos in a bacterial stress response.

Cellular responses to environmental changes are often highly heterogeneous and exhibit seemingly random dynamics. The astonishing insight of chaos theory is that such unpredictable patterns can, in principle, arise without the need for any random processes, i.e., purely deterministically without noise. However, while chaos is well understood in mathematics and physics, its role in cell biology remains unclear because the complexity and noisiness of biological systems make testing difficult. Here, we show that chaos explains the heterogeneous response of Escherichia coli cells to oxidative stress. We developed a theoretical model of the gene expression dynamics and demonstrate that chaotic behavior arises from rapid molecular feedbacks that are coupled with cell growth dynamics and cell-cell interactions. Based on theoretical predictions, we then designed single-cell experiments to show we can shift gene expression from periodic oscillations to chaos on demand. Our work suggests that chaotic gene regulation can be employed by cell populations to generate strong and variable responses to changing environments.

Burn Center Patients at Risk for Upper Extremity Amputations.

Introduction Burn center patients present not only with burn injuries but also necrotizing infections, purpura fulminans, frostbite, toxic epidermal necrolysis, chronic wounds, and trauma. Burn surgeons are often faced with the need to amputate when limb salvage is no longer a viable option. The purpose of this study was to determine factors which predispose patients to extremity amputations. Methods: This retrospective registry review (2000-2019) compared patients who required upper extremity amputations with those who did not. Cases were pair-matched by age, sex, percent total body surface area (%TBSA), and type/location of injury to control for possible confounding variables. Results: There were 77 upper extremity amputee patients (APs) and 77 pair-matched non-amputees (NAPs) with the median age 45- and 43-years, %TBSA 21 and 10, respectively; second and third degree burn injuries were similar in the 2 groups. The AP group had longer hospitalizations (median 40 vs 15 days) P < .0001, with more intensive care unit days (median 28 vs 18 days). APs presented with significantly more cardiac, renal, and pulmonary comorbidities, acquired infections (61 [64%] vs 35 [36%]), escharotomies, and fasciotomies than the NAP, P < .0001. Mortality was similar (AP 14 [18.2%] vs NAP 9 [11.7%]), P = .26. Conclusions: Escharotomies, fasciotomies, sepsis, pneumonia, wound, and urinary tract infections contributed to prolonged hospitalizations and increased risk for upper extremity amputations in the AP group.

Introduction Les patients des centres de grands brûlés ne présentent pas seulement des lésions dues aux brûlures, mais aussi des infections nécrosantes, un purpura fulminans, des gelures, une épidermolyse bulleuse toxique, des plaies chroniques et des traumatismes. Les chirurgiens pour brûlés sont souvent confrontés au besoin d'amputer quand le sauvetage d'un membre n'est plus une option valable. L'objectif de cette étude était de déterminer les facteurs prédisposant les patients aux amputations de membres. Méthodes: Cette analyse rétrospective d'un registre (2000-2019) a comparé les patients ayant nécessité une amputation d'un membre supérieur à ceux pour lesquels l'amputation n'a pas été nécessaire. Les cas ont été appariés par âge, sexe, pourcentage de la surface corporelle totale (%SCT) et le type/emplacement des lésions pour contrôler les possibles variables confondantes. Résultats: Il y a eu 77 patients amputés (PA) du membre supérieur et 77 patients non amputés (PNA) appariés ayant, respectivement, un âge médian de 45 et 43 ans et un %SCT de 21% et 10%; les lésions par brûlures des 2e et 3e degrés étaient similaires dans les deux groupes. La durée d'hospitalisation pour le groupe PA a été plus longue que pour le groupe PNA (médiane : 40 jours contre 15 jours; P < .0001) avec un plus grand nombre de jours en unité de soins intensifs (médiane : 28 jours contre 18 jours). Les patients du groupe PA avaient plus de comorbidités cardiaques, rénales et pulmonaires et d'infections acquises (61 [64%] contre 35 [36%]), d'escarrotomies et d'aponévrotomies que les patients du groupe PNA (P <.0001). La mortalité a été semblable dans les deux groupes (PA: 14 [18.2%] contre PNA: 9 [11.7%], P = .26). Conclusion: Les incisions de décharge, les aponévrotomies, le sepsis, les pneumonies, les infections des plaies et des voies urinaires ont contribué à des hospitalisations prolongées et à une augmentation du risque d'amputation du membre supérieur dans le groupe PA.

Time delays modulate the stability of complex ecosystems.

What drives the stability, or instability, of complex ecosystems? This question sits at the heart of community ecology and has motivated a large body of theoretical work exploring how community properties shape ecosystem dynamics. However, the overwhelming majority of current theory assumes that species interactions are instantaneous, meaning that changes in the abundance of one species will lead to immediate changes in the abundances of its partners. In practice, time delays in how species respond to one another are widespread across ecological contexts, yet the impact of these delays on ecosystems remains unclear. Here we derive a new body of theory to comprehensively study the impact of time delays on ecological stability. We find that time delays are important for ecosystem stability. Large delays are typically destabilizing but, surprisingly, short delays can substantially increase community stability. Moreover, in stark contrast to delay-free systems, delays dictate that communities with more abundant species can be less stable than ones with less abundant species. Finally, we show that delays fundamentally shift how species interactions impact ecosystem stability, with communities of mixed interaction types becoming the most stable class of ecosystem. Our work demonstrates that time delays can be critical for the stability of complex ecosystems.

Higher Initial Formula for Resuscitation After Severe Burn Injury Means Higher 24-Hour Volumes.

Initial fluid infusion rates for resuscitation of burn injuries typically use formulas based on patient weight and total body surface area (TBSA) burned. However, the impact of this rate on overall resuscitation volumes and outcomes have not been extensively studied. The purpose of this study was to determine the impact of initial fluid rates on 24-hour volumes and outcomes using the Burn Navigator (BN). The BN database is composed of 300 patients with ≥20% TBSA, >40 kg that were resuscitated utilizing the BN. Four study arms were analyzed based on the initial formula-2 ml/kg/TBSA, 3 ml/kg/TBSA, 4 ml/kg/TBSA or the Rule of Ten. Total fluids infused at 24 hours after admission were compared as well as resuscitation-related outcomes. A total of 296 patients were eligible for analysis. Higher starting rates (4 ml/kg/TBSA) resulted in significantly higher volumes at 24 hours (5.2 ± 2.2 ml/kg/TBSA) than lower rates (2 ml/kg/TBSA resulted in 3.9 ± 1.4 ml/kg/TBSA). No shock was observed in the high resuscitation cohort, whereas the lowest starting rate exhibited a 12% incidence, lower than both the Rule of Ten and 3 ml/kg/TBSA arms. There was no difference in 7-day mortality across groups. Higher initial fluid rates resulted in higher 24-hour fluid volumes. The choice of 2ml/kg/TBSA as initial rate did not result in increased mortality or more complications. An initial rate of 2ml/kg/TBSA is a safe strategy.

Predictors and Impact of Pneumonia on Adverse Outcomes in Inhalation Injury Patients.

Inhalation injury (II) is the third mortality prognostic factor for burn injury following age and burn size. II can lead to pulmonary complications such as pneumonia and acute respiratory distress syndrome (ARDS); all of which have been hypothesized to increase morbidity and mortality in II. Herein, we aimed to identify variables associated with the risk of developing pneumonia and to determine the impact of pneumonia on selected II outcomes. De-identified data from the Prospective Inhalation Study titled Inhalation Injury Scoring System to Predict Inhalation Injury Severity (ISIS) were used. II was confirmed by fiberoptic bronchoscopy. Demographics, injury, and hospital course information were recorded. P < .05 was considered significant. One hundred subjects were included. On univariate analysis, pneumonia was associated with burn severity, race, and receipt of colloid during the first 24 hours. Patients who developed pneumonia spent more time on a ventilator, had longer hospitalizations (LOS) and were more likely to need a tracheostomy. On multivariate analysis, total number of ventilator days was associated with pneumonia (Odd ratio (OR) = 1.122 [1.048-1.200], P = .001). Both pneumonia and receipt of colloid were predictive of increased ventilator days (OR = 2.545 [1.363-4.753], P < .001 and OR = 2.809 [1.548-5.098], P < .001, respectively). Pneumonia was not an independent predictor of LOS, ARDS, or mortality. Pneumonia remains a high-risk complication associated with two times more ventilator days in II. Future research should focus on prevention of pneumonia and the relationship between colloid fluids and pneumonia and early ventilator liberation in II patients.

Impact of Alcohol and Methamphetamine Use on Burn Resuscitation.

Mortality associated with burn injuries is declining with improved critical care. However, patients admitted with concurrent substance use have increased risk of complications and poor outcomes. The impact of alcohol and methamphetamine use on acute burn resuscitation has been described in single-center studies; however, has not been studied since implementation of computerized decision support for resuscitation. Patients were evaluated based presence of alcohol, with a minimum blood alcohol level of 0.10, or positive methamphetamines on urine drug screen. Fluid volumes and urine output were examined over 48 hours. A total of 296 patients were analyzed. 37 (12.5%) were positive for methamphetamine use, 50 (16.9%) were positive for alcohol use, and 209 (70.1%) with negative for both. Patients positive for methamphetamine received a mean of 5.30 ± 2.63 cc/kg/TBSA, patients positive for alcohol received a mean of 5.41 ± 2.49 cc/kg/TBSA, and patients with neither received a mean of 4.33 ± 1.79 cc/kg/TBSA. Patients with methamphetamine or alcohol use had significantly higher fluid requirements. In the first 6 hours patients with alcohol use had significantly higher urinary output (UO) in comparison to patients with methamphetamine use which had similar output to patients negative for both substances. This study demonstrated that patients with alcohol and methamphetamine use had statistically significantly greater fluid resuscitation requirements compared to patients without. The effects of alcohol as a diuretic align with previous literature. However, patients with methamphetamine lack the increased UO as a cause for their increased fluid requirements.

Leaf formononetin content of Trifolium subterraneum increases in response to waterlogging but its proportion of total isoflavones is little changed.

The isoflavone formononetin (F) impacts livestock fertility and cultivars of the pasture legume Trifolium subterraneum L. (subclover) have been selected for F levels ≤0.2% of leaf dry weight. However, the impact of waterlogging (WL) on isoflavones is little studied. We investigated the response of isoflavones, biochanin A (BA), genistein (G) and F, to WL for: (1) Yarloop (high F) and eight low F cultivars each from subspecies subterraneum , brachycalycinum and yanninicum (Experiment 1); and (2) four cultivars and 12 ecotypes of ssp. yanninicum (Experiment 2). WL impacted F: estimated means increased from 0.19% (control) to 0.31% (WL) in Experiment 1 and from 0.61% to 0.97% in Experiment 2. Isoflavones under WL were highly heritable, particularly F (H 2 =95%). The proportions of BA, G and F were little changed by WL, with strong positive correlations between free-drained and waterlogged treatments. Isoflavone contents were not related to WL tolerance, as assessed by shoot relative growth rate. In conclusion, isoflavones varied among genotypes and increased with WL, but the proportion of individual isoflavones in each genotype was stable. High F under WL was unrelated with genotype tolerance to WL. Instead, it was a consequence of inherently high F for that particular genotype.

Bacterial defences: mechanisms, evolution and antimicrobial resistance.

Throughout their evolutionary history, bacteria have faced diverse threats from other microorganisms, including competing bacteria, bacteriophages and predators. In response to these threats, they have evolved sophisticated defence mechanisms that today also protect bacteria against antibiotics and other therapies. In this Review, we explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. We also review the countermeasures that attackers have evolved to overcome bacterial defences. We argue that understanding how bacteria defend themselves in nature is important for the development of new therapies and for minimizing resistance evolution.

Collective protection against the type VI secretion system in bacteria.

Bacteria commonly face attacks from other strains using the type VI secretion system (T6SS), which acts like a molecular speargun to stab and intoxicate competitors. Here we show how bacteria can work together to collectively defend themselves against these attacks. This project began with an outreach activity: while developing an online computer game of bacterial warfare, we noticed that one strategist ("Slimy") that made extracellular polymeric substances (EPS) was able to resist attacks from another strategist that employed the T6SS ("Stabby"). This observation motivated us to model this scenario more formally, using dedicated agent-based simulations. The model predicts that EPS production can serve as a collective defence mechanism, which protects both producing cells and neighbouring cells that do not make EPS. We then tested our model with a synthetic community that contains a T6SS-wielding attacker (Acinetobacter baylyi), and two T6SS-sensitive target strains (Escherichia coli) that either secrete EPS, or not. As predicted by our modelling, we find that the production of EPS leads to collective protection against T6SS attacks, where EPS producers protect each other and nearby non-producers. We identify two processes that explain this protection: EPS sharing between cells and a second general mechanism whereby groups of resistant cells shield susceptible cells, which we call "flank protection". Our work shows how EPS-producing bacteria can work together to defend themselves from the type VI secretion system.

Phenotypic heterogeneity in the bacterial oxidative stress response is driven by cell-cell interactions.

Genetically identical bacterial cells commonly display different phenotypes. This phenotypic heterogeneity is well known for stress responses, where it is often explained as bet hedging against unpredictable environmental threats. Here, we explore phenotypic heterogeneity in a major stress response of Escherichia coli and find it has a fundamentally different basis. We characterize the response of cells exposed to hydrogen peroxide (H2O2) stress in a microfluidic device under constant growth conditions. A machine-learning model reveals that phenotypic heterogeneity arises from a precise and rapid feedback between each cell and its immediate environment. Moreover, we find that the heterogeneity rests upon cell-cell interaction, whereby cells shield each other from H2O2 via their individual stress responses. Our work shows how phenotypic heterogeneity in bacterial stress responses can emerge from short-range cell-cell interactions and result in a collective phenotype that protects a large proportion of the population.