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Abstract We report the case of a 79-year-old woman with Alzheimer’s disease who participated in a Phase III randomized controlled trial called CLARITY-AD testing the experimental drug lecanemab. She was randomized to the placebo group and subsequently enrolled in an open-label extension which guaranteed she received the active drug. After the third biweekly infusion, she suffered a seizure characterized by speech arrest and a generalized convulsion. Magnetic resonance imaging revealed she had multifocal swelling and a marked increase in the number of cerebral microhemorrhages. She was treated with an antiepileptic regimen and high-dose intravenous corticosteroids but continued to worsen and died after 5 days. Post-mortem MRI confirmed extensive microhemorrhages in the temporal, parietal and occipital lobes. The autopsy confirmed the presence of two copies of APOE4, a gene associated with a higher risk of Alzheimer’s disease, and neuropathological features of moderate severity Alzheimer’s disease and severe cerebral amyloid angiopathy with perivascular lymphocytic infiltrates, reactive macrophages and fibrinoid degeneration of vessel walls. There were deposits of β-amyloid in meningeal vessels and penetrating arterioles with numerous microaneurysms. We conclude that the patient likely died as a result of severe cerebral amyloid-related inflammation.

Backgrounds & Aims: Bile acids (BAs) are core gastrointestinal metabolites with dual functions in lipid absorption and cell signaling. BAs circulate between the liver and distal small intestine (i.e., ileum), yet the dynamics through which complex BA pools are absorbed in the ileum and interact with host intestinal cells in vivo remain poorly understood. Because ileal absorption is rate-limiting in determining which BAs in the intestinal lumen gain access to host intestinal cells and receptors, and at what concentrations, we hypothesized that defining the rates and routes of ileal BA absorption in vivo would yield novel insights into the physiological forms and functions of mouse enterohepatic BA pools. Methods: Using ex vivo mass spectrometry, we quantified 88 BA species and metabolites in the intestinal lumen and superior mesenteric vein of individual wild-type mice, and cage-mates lacking the ileal BA transporter, Asbt/Slc10a2. Results: Using these data, we calculated that the pool of BAs circulating through ileal tissue (i.e., the ileal BA pool) in fasting C57BL/6J female mice is ∼0.3 μmol/g. Asbt-mediated transport accounted for ∼80% of this pool and amplified size. Passive permeability explained the remaining ∼20% and generated diversity. Compared with wild-type mice, the ileal BA pool in Asbt-deficient mice was ∼5-fold smaller, enriched in secondary BA species and metabolites normally found in the colon, and elicited unique transcriptional responses on addition to ex vivo–cultured ileal explants. Conclusions: This study defines quantitative traits of the mouse enterohepatic BA pool and reveals how aberrant BA metabolism can impinge directly on host intestinal physiology.

ABSTRACT Daniel Schultz works at the intersection of microbiology and biological physics. In this mSphere of Influence article, he reflects on how two papers concerning the radio, “Can a biologist fix a radio? Or, what I learned while studying apoptosis” by Yuri Lazebnik and “The evolved radio and its implications for modeling the evolution of novel sensors” by Jon Bird and Paul Layzell, offered him complementary perspectives on how to bridge the gap between engineering and biology in the study of cellular circuits.

Interspecies interactions can drive the emergence of unexpected microbial phenotypes that are not observed when studying monocultures. The cystic fibrosis (CF) lung consists of a complex environment where microbes, living as polymicrobial biofilm-like communities, are associated with negative clinical outcomes for persons with CF (pwCF). However, the current lack of in vitro models integrating the microbial diversity observed in the CF airway hampers our understanding of why polymicrobial communities are recalcitrant to therapy in this disease. Here, integrating computational approaches informed by clinical data, we built a mixed community of clinical relevance to the CF lung composed of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis, and Prevotella melaninogenica. We developed and validated this model biofilm community with multiple isolates of these four genera. When challenged with tobramycin, a front-line antimicrobial used to treat pwCF, the microorganisms in the polymicrobial community show altered sensitivity to this antibiotic compared to monospecies biofilms. We observed that wild-type P. aeruginosa is sensitized to tobramycin in a mixed community versus monoculture, and this observation holds across a range of community relative abundances. We also report that LasR loss-of-function, a variant frequently detected in the CF airway, drives tolerance of P. aeruginosa to tobramycin specifically in the mixed community. Our data suggest that the molecular basis of this community-specific recalcitrance to tobramycin for the P. aeruginosa lasR mutant is increased production of phenazines. Our work supports the importance of studying a clinically relevant model of polymicrobial biofilms to understand community-specific traits relevant to infections.

Nondestructive evaluation methods play an important role in ensuring component integrity and safety in many industries. Operator fatigue can play a critical role in the reliability of such methods. This is important for inspecting high value assets or assets with a high consequence of failure, such as aerospace and nuclear components. Recent advances in convolution neural networks can support and automate these inspection efforts. This paper proposes using residual neural networks (ResNets) for real-time detection of corrosion, including iron oxide discoloration, pitting and stress corrosion cracking, in dry storage stainless steel canisters housing used nuclear fuel. The proposed approach crops nuclear canister images into smaller tiles, trains a ResNet on these tiles, and classifies images as corroded or intact using the per-image count of tiles predicted as corroded by the ResNet. The results demonstrate that such a deep learning approach allows to detect the locus of corrosion via smaller tiles, and at the same time to infer with high accuracy whether an image comes from a corroded canister. Thereby, the proposed approach holds promise to automate and speed up nuclear fuel canister inspections, to minimize inspection costs, and to partially replace human-conducted onsite inspections, thus reducing radiation doses to personnel.

Microbes frequently evolve in reproducible ways. Here, we show that differences in specific metabolic regulation rather than inter-strain interactions explain the frequent presence of lasR loss-of-function (LOF) mutations in the bacterial pathogen Pseudomonas aeruginosa. While LasR contributes to virulence through its role in quorum sensing, lasR mutants have been associated with more severe disease. A model based on the intrinsic growth kinetics for a wild type strain and its LasR– derivative, in combination with an experimental evolution based genetic screen and further genetics analyses, indicated that differences in metabolism were sufficient to explain the rise of these common mutant types. The evolution of LasR– lineages in laboratory and clinical isolates depended on activity of the two-component system CbrAB, which modulates substrate prioritization through the catabolite repression control pathway. LasR– lineages frequently arise in cystic fibrosis lung infections and their detection correlates with disease severity. Our analysis of bronchoalveolar lavage fluid metabolomes identified compounds that negatively correlate with lung function, and we show that these compounds support enhanced growth of LasR– cells in a CbrB-controlled manner. We propose that in vivo metabolomes contribute to pathogen evolution, which may influence the progression of disease and its treatment.

Antibiotic treatments often fail to eliminate bacterial populations due to heterogeneity in how individual cells respond to the drug. In structured bacterial populations such as biofilms, bacterial metabolism and environmental transport processes lead to an emergent phenotypic structure and self-generated nutrient gradients toward the interior of the colony, which can affect cell growth, gene expression and susceptibility to the drug. Even in single cells, survival depends on a dynamic interplay between the drug’s action and the expression of resistance genes. How expression of resistance is coordinated across populations in the presence of such spatiotemporal environmental coupling remains elusive. Using a custom microfluidic device, we observe the response of spatially extended microcolonies of tetracycline-resistant E. coli to precisely defined dynamic drug regimens. We find an intricate interplay between drug-induced changes in cell growth and growth-dependent expression of resistance genes, resulting in the redistribution of metabolites and the reorganization of growth patterns. This dynamic environmental feedback affects the regulation of drug resistance differently across the colony, generating dynamic phenotypic structures that maintain colony growth during exposure to high drug concentrations and increase population-level resistance to subsequent exposures. A mathematical model linking metabolism and the regulation of gene expression is able to capture the main features of spatiotemporal colony dynamics. Uncovering the fundamental principles that govern collective mechanisms of antibiotic resistance in spatially extended populations will allow the design of optimal drug regimens to counteract them.

ABSTRACT During biofilm formation, the opportunistic pathogen Pseudomonas aeruginosa uses its type IV pili (TFP) to sense a surface, eliciting increased second-messenger production and regulating target pathways required to adapt to a surface lifestyle. The mechanisms whereby TFP detect surface contact are still poorly understood, although mechanosensing is often invoked, with few data supporting this claim. Using a combination of molecular genetics and single-cell analysis, with biophysical, biochemical, and genomics techniques, we show that force-induced changes mediated by the von Willebrand A (vWA) domain-containing, TFP tip-associated protein PilY1 are required for surface sensing. Atomic force microscopy shows that TFP/PilY1 can undergo force-induced, sustained conformational changes akin to those observed for mechanosensitive proteins like titin. We show that mutation of a single cysteine residue in the vWA domain of PilY1 results in modestly lower surface adhesion forces, reduced sustained conformational changes, and increased nanospring-like properties, as well as reduced c-di-GMP signaling and biofilm formation. Mutating this cysteine has allowed us to genetically separate a role for TFP in twitching motility from surface-sensing signaling. The conservation of this Cys residue in all P. aeruginosa PA14 strains and its absence in the ∼720 sequenced strains of P. aeruginosa PAO1 may contribute to explaining the observed differences in surface colonization strategies observed for PA14 versus PAO1. IMPORTANCE Most bacteria live on abiotic and biotic surfaces in surface-attached communities known as biofilms. Surface sensing and increased levels of the second-messenger molecule c-di-GMP are crucial to the transition from planktonic to biofilm growth. The mechanism(s) underlying TFP-mediated surface detection that triggers this c-di-GMP signaling cascade is unclear. Here, we provide key insight into this question; we show that the eukaryote-like vWA domain of the TFP tip-associated protein PilY1 responds to mechanical force, which in turn drives the production of a key second messenger needed to regulate surface behaviors. Our studies highlight a potential mechanism that may account for differing surface colonization strategies.

A recent workshop titled “Developing Models to Study Polymicrobial Infections,” sponsored by the Dartmouth Cystic Fibrosis Center (DartCF), explored the development of new models to study the polymicrobial infections associated with the airways of persons with cystic fibrosis (CF). The workshop gathered 35+ investigators over two virtual sessions.

ABSTRACT Seasonal influenza outbreaks represent a large burden for the health care system as well as the economy. While the role of the microbiome has been elucidated in the context of various diseases, the impact of respiratory viral infections on the human microbiome is largely unknown. In this study, swine was used as an animal model to characterize the temporal dynamics of the respiratory and gastrointestinal microbiome in response to an influenza A virus (IAV) infection. A multi-omics approach was applied on fecal samples to identify alterations in microbiome composition and function during IAV infection. We observed significantly altered microbial richness and diversity in the gastrointestinal microbiome after IAV infection. In particular, increased abundances of Prevotellaceae were detected, while Clostridiaceae and Lachnospiraceae decreased. Moreover, our metaproteomics data indicated that the functional composition of the microbiome was heavily affected by the influenza infection. For instance, we identified decreased amounts of flagellin, correlating with reduced abundances of Lachnospiraceae and Clostridiaceae, possibly indicating involvement of a direct immune response toward flagellated Clostridia during IAV infection. Furthermore, enzymes involved in short-chain fatty acid (SCFA) synthesis were identified in higher abundances, while metabolome analyses revealed rather stable concentrations of SCFAs. In addition, 16S rRNA gene sequencing was used to characterize effects on the composition and natural development of the upper respiratory tract microbiome. Our results showed that IAV infection resulted in significant changes in the abundance of Moraxellaceae and Pasteurellaceae in the upper respiratory tract. Surprisingly, temporal development of the respiratory microbiome structure was not affected. IMPORTANCE Here, we used swine as a biomedical model to elucidate the impact of influenza A H1N1 infection on structure and function of the respiratory and gastrointestinal tract microbiome by employing a multi-omics analytical approach. To our knowledge, this is the first study to investigate the temporal development of the porcine microbiome and to provide insights into the functional capacity of the gastrointestinal microbiome during influenza A virus infection.

Seasonal influenza epidemics pose a considerable hazard for global health. In the past decades, accumulating evidence revealed that influenza A virus (IAV) renders the host vulnerable to bacterial superinfections which in turn are a major cause for morbidity and mortality. However, whether the impact of influenza on anti-bacterial innate immunity is restricted to the vicinity of the lung or systemically extends to remote sites is underexplored. We therefore sought to investigate intranasal infection of adult C57BL/6J mice with IAV H1N1 in combination with bacteremia elicited by intravenous application of Group A Streptococcus (GAS). Co-infection in vivo was supplemented in vitro by challenging murine bone marrow derived macrophages and exploring gene expression and cytokine secretion. Our results show that viral infection of mice caused mild disease and induced the depletion of CCL2 in the periphery. Influenza preceding GAS infection promoted the occurrence of paw edemas and was accompanied by exacerbated disease scores. In vitro co-infection of macrophages led to significantly elevated expression of TLR2 and CD80 compared to bacterial mono-infection, whereas CD163 and CD206 were downregulated. The GAS-inducible upregulation of inflammatory genes, such as Nos2, as well as the secretion of TNFα and IL-1β were notably reduced or even abrogated following co-infection. Our results indicate that IAV primes an innate immune layout that is inadequately equipped for bacterial clearance.

Objectives: The aim of this study was to evaluate the prognostic value of peritoneal cytology status among other clinicopathological parameters in uterine serous carcinoma (USC). Methods: A retrospective study of 148 patients diagnosed with uterine serous carcinoma from 1997 to 2016 at two academic medical centers in the Detroit metropolitan area was done. A central gynecologic pathologist reviewed all available slides and confirmed the histologic diagnosis of each case of USC. We assessed the prognostic impact of various clinicopathological parameters on overall survival (OS) and endometrial cancer-specific survival (ECSS). Those parameters included race, body mass index (BMI), stage at diagnosis, tumor size, lymphovascular invasion (LVSI), peritoneal cytology status, receipt of adjuvant treatment, and comorbidity count using the Charlson Comorbidity Index (CCI). We used Cox proportional hazards models and 95% confidence intervals for statistical analysis. Results: Positive peritoneal cytology had a statistically significant effect on OS (HR: 2.09, 95% CI: [1.19, 3.68]) and on ECSS (HR: 2.02, 95% CI: [1.06 – 3.82]). LVSI had a statistically significant effect on both OS (HR: 2.27, 95% CI: [1.14, 4.53]) and ECSS (HR: 3.45, 95% CI: [1.49, 7.99]). Black or African American (AA) race was also found to have a significant effect on both OS (HR: 1.92, 95% CI: [1.07, 3.47]) and ECSS (HR: 2.01, 95% CI: [1.02, 3.98]). Other factors including BMI and tumor size > 1 cm did not show a statistically significant impact on OS or ECSS. Conclusions: Peritoneal washings with positive cytology and LVSI are important prognostic tools that may have a significant impact on overall survival in USC and can be used as independent negative prognosticators to help guide adjuvant treatment.

A prominent feature of severe streptococcal infections is the profound inflammatory response that contributes to systemic toxicity. In sepsis the dysregulated host response involves both immunological and nonimmunological pathways. Here, we report a fatal case of an immunocompetent healthy female presenting with toxic shock and purpura fulminans caused by group B streptococcus (GBS; serotype III, CC19). The strain (LUMC16) was pigmented and hyperhemolytic. Stimulation of human primary cells with hyperhemolytic LUMC16 and STSS/NF-HH strains and pigment toxin resulted in a release of proinflammatory mediators, including tumor necrosis factor, interleukin (IL)-1β, and IL-6. In addition, LUMC16 induced blood clotting and showed factor XII activity on its surface, which was linked to the presence of the pigment. The expression of pigment was not linked to a mutation within the CovR/S region. In conclusion, our study shows that the hemolytic lipid toxin contributes to the ability of GBS to cause systemic hyperinflammation and interferes with the coagulation system.

Pneumonia is an infection of the lungs, where the alveoli in the affected area are filled with pus and fluid. Although ventilated patients are at risk, not all ventilated patients develop pneumonia. This suggests that the sputum environment may possess antimicrobial activities. Despite the generally acknowledged importance of antimicrobial activity in protecting the human lung against infections, this has not been systematically assessed to date. Therefore, the objective of the present study was to measure antimicrobial activity in broncho-alveolar aspirate (‘sputum”) samples from patients in an intensive care unit (ICU) and to correlate the detected antimicrobial activity with antibiotic levels, the sputum microbiome, and the respective patients’ characteristics. To this end, clinical metadata and sputum were collected from 53 mechanically ventilated ICU patients. The antimicrobial activity of sputum samples was tested against Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus anginosus. Here we show that sputa collected from different patients presented a high degree of variation in antimicrobial activity, which can be partially attributed to antibiotic therapy. The sputum microbiome, although potentially capable of producing antimicrobial agents, seemed to contribute in a minor way, if any, to the antimicrobial activity of sputum. Remarkably, despite its potentially protective effect, the level of antimicrobial activity in the investigated sputa correlated inversely with patient outcome, most likely because disease severity outweighed the beneficial antimicrobial activities.

Septic arthritis is a medical emergency associated with high morbidity and mortality, yet hardly any novel advances exist for its clinical management. Despite septic arthritis being a global health burden, experimental data uncovering its etiopathogenesis remain scarce. In particular, any interplay between septic arthritis and preceding joint diseases are unknown as is the contribution of the synovial membrane to the onset of inflammation. Using C57BL/6 mice as a model to study sepsis, we discovered that Group A Streptococcus (GAS) – an important pathogen causing septic arthritis - was able to invade the articular microenvironment. Bacterial invasion resulted in the infiltration of immune cells and detrimental inflammation. In vitro infected fibroblast-like synoviocytes induced the expression of chemokines (Ccl2, Cxcl2), inflammatory cytokines (Tnf, Il6), and integrin ligands (ICAM-1, VCAM-1). Apart from orchestrating immune cell attraction and retention, synoviocytes also upregulated mediators impacting on bone remodeling (Rankl) and cartilage integrity (Mmp13). Using collagen-induced arthritis in DBA/1 × B10.Q F1 mice, we could show that an inflammatory joint disease exacerbated subsequent septic arthritis which was associated with an excessive release of cytokines and eicosanoids. Importantly, the severity of joint inflammation controlled the extent of bone erosions during septic arthritis. In order to ameliorate septic arthritis, our results suggest that targeting synoviocytes might be a promising approach when treating patients with inflammatory joint disease for sepsis.

In experimental evolution, scientists evolve organisms in the lab, typically by challenging them to new environmental conditions. How best to evolve a desired trait? Should the challenge be applied abruptly, gradually, periodically, sporadically? Should one apply chemical mutagenesis, and do strains with high innate mutation rate evolve faster? What are ideal population sizes of evolving populations? There are endless strategies, beyond those that can be exposed by individual labs. We therefore arranged a community challenge, Evolthon, in which students and scientists from different labs were asked to evolve Escherichia coli or Saccharomyces cerevisiae for an abiotic stress-low temperature. About 30 participants from around the world explored diverse environmental and genetic regimes of evolution. After a period of evolution in each lab, all strains of each species were competed with one another. In yeast, the most successful strategies were those that used mating, underscoring the importance of sex in evolution. In bacteria, the fittest strain used a strategy based on exploration of different mutation rates. Different strategies displayed variable levels of performance and stability across additional challenges and conditions. This study therefore uncovers principles of effective experimental evolutionary regimens and might prove useful also for biotechnological developments of new strains and for understanding natural strategies in evolutionary arms races between species. Evolthon constitutes a model for community-based scientific exploration that encourages creativity and cooperation.

Swine are regarded as promising biomedical models, but the dynamics of their gastrointestinal microbiome have been much less investigated than that of humans or mice. The aim of this study was to establish an integrated multi-omics protocol to investigate the fecal microbiome of healthy swine. To this end, a preparation and analysis protocol including integrated sample preparation for meta-omics analyses of deep-frozen feces was developed. Subsequent data integration linked microbiome composition with function, and metabolic activity with protein inventories, i.e., 16S rRNA data and expressed proteins, and identified proteins with corresponding metabolites. 16S rRNA gene amplicon and metaproteomics analyses revealed a fecal microbiome dominated by Prevotellaceae, Lactobacillaceae, Lachnospiraceae, Ruminococcaceae and Clostridiaceae. Similar microbiome compositions in feces and colon, but not ileum samples, were observed, showing that feces can serve as minimal-invasive proxy for porcine colon microbiomes. Longitudinal dynamics in composition, e.g., temporal decreased abundance of Lactobacillaceae and Streptococcaceae during the experiment, were not reflected in microbiome function. Instead, metaproteomics and metabolomics showed a rather stable functional state, as evident from short-chain fatty acids (SCFA) profiles and associated metaproteome functions, pointing towards functional redundancy among microbiome constituents. In conclusion, our pipeline generates congruent data from different omics approaches on the taxonomy and functionality of the intestinal microbiome of swine.

Respiratory tract infections are a global health problem. The main causative agents of these infections are influenza A virus (IAV), Staphylococcus aureus (S. aureus), and Streptococcus pneumoniae (S. pneumoniae). Major research focuses on genetics and immune responses in these infections. Eicosanoids and other oxylipins are host-derived lipid mediators that play an important role in the activation and resolution of inflammation. In this study, we assess, for the first time, the different intracellular profiles of these bioactive lipid mediators during S. aureus LUG2012, S. pneumoniae TIGR4, IAV, and corresponding viral and bacterial co-infections of 16HBE cells. We observed a multitude of altered lipid mediators. Changes in the amount of 5-hydroxyeicosatetraenoic acid (5-HETE) were prominent for all bacterial infections. The infection with S. pneumoniae showed the strongest impact on bioactive lipid production and led to alterations in the amount of PPARγ ligands and precursors of pro-resolving lipid mediators.

Respiratory tract infections caused by the Influenza A virus (IAV) are a worldwide problem for human and animal health. Within this study, we analyzed the impact of IAV infection on the immune-related lipidome (eicosanoids) of the pig as new infection model. For this purpose, we performed HPLC-MS/MS using dynamic multiple reaction monitoring and analyzed lung, spleen, blood plasma and bronchoalveolar lavages. IAV infection leads to collective changes in the levels of the analyzed hydroxyeicosatrienoic acids (HETEs), hydroxydocosahexaenoic acids (HDHAs) and epoxyeicosatrienoic acids (EETs), and moreover, unique eicosanoid changes in several sample types, even under mild infection conditions. In accordance with different mouse infection studies, we observed infection-related patterns for 12-HETE, 15-HETE and 17-HDHA, which seem to be common for IAV infection. Using a long-term approach of 21 days we established an experimental setup that can be used also for bacterial-viral coinfection experiments.

Purpose: Although the majority of recurrences occur within the first 3 years of hysterectomy for endometrioid carcinoma, we report herein a successful salvage vaginal brachytherapy in a patient with endometrioid uterine carcinoma which recurred more than 17 years after initial treatment. Materials and Methods: A 61-year-old female was diagnosed with endometrioid adenocarcinoma of the uterus and treated with TAH-BSO, followed by adjuvant external beam radiation therapy (EBRT) to the whole pelvis. After remaining free of any recurrent or metastatic disease for more than 17 years, she was diagnosed with isolated vaginal cuff recurrence and successfully treated with a salvage high-dose-rate intracavitary vaginal brachytherapy. Results: The patient remained disease free until her death from unrelated causes 7 years later. Conclusion: To the best of our knowledge, this case represents the longest time to recurrence of endometrial cancer in someone who had been treated with TAH-BSO and adjuvant pelvic EBRT. This case highlights that even with adjuvant therapy, late recurrences may occur, and successful salvage brachytherapy is very effective.

Proteolysis is essential for all living organisms to maintain the protein homeostasis and to adapt to changing environmental conditions. ClpP is the main protease in Bacillus subtilis, and forms complexes with different Clp ATPases. These complexes play crucial roles during heat stress, but also in sporulation or cell morphology. Especially enzymes of cell wall-, amino acid-, and nucleic acid biosynthesis are known substrates of the protease ClpP during glucose starvation. The aim of this study was to analyze the influence of a clpP mutation on the metabolism in different growth phases and to search for putative new ClpP substrates. Therefore, B. subtilis 168 cells and an isogenic ∆clpP mutant were cultivated in a chemical defined medium, and the metabolome was analyzed by a combination of 1H-NMR, HPLC-MS, and GC-MS. Additionally, the cell morphology was investigated by electron microscopy. The clpP mutant showed higher levels of most glycolytic metabolites, the intermediates of the citric acid cycle, amino acids, and peptidoglycan precursors when compared to the wild-type. A strong secretion of overflow metabolites could be detected in the exo-metabolome of the clpP mutant. Furthermore, a massive increase was observed for the teichoic acid metabolite CDP-glycerol in combination with a swelling of the cell wall. Our results show a recognizable correlation between the metabolome and the corresponding proteome data of B. subtilis clpP mutant. Moreover, our results suggest an influence of ClpP on Tag proteins that are responsible for teichoic acids biosynthesis.

The corallivorous crown-of-thorns starfish (Acanthaster spp.) is a major cause of coral mortality on Indo-Pacific reefs. Despite considerable research into the biology of crown-of-thorns starfish, our understanding of the early post-settlement life stage has been hindered by the small size and cryptic nature of recently settled individuals. Most growth rates are derived from either laboratory studies or field studies conducted in Fiji and Japan. The Great Barrier Reef (GBR) is currently experiencing its fourth recorded outbreak and population models to inform the progression of outbreaks lack critical growth rates of early life history stages. High numbers of 0+ year juveniles (n = 3532) were measured during extensive surveys of 64 reefs on the northern GBR between May and December 2015. An exponential growth model was fitted to the size measurement data to estimate monthly ranges of growth rates for 0+ year juveniles. Estimated growth rates varied considerably and increased with age (e.g., 0.028–0.041 mm·day−1 for one-month-old juveniles versus 0.108–0.216 mm·day−1 for twelve-month-old juveniles). This pioneering study of 0+ year juveniles on the GBR will inform population models and form the basis for more rigorous ongoing research to understand the fate of newly settled Acanthaster spp.