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• The fate of FIB and of pathogenic bacteria though AD varied with the biogas plant. • log 10 reductions of pathogenic bacteria though AD varied over time. • Campylobacter and Salmonella were less persistent than L. monocytogenes. • The reduction of C. botulinum and C. difficile were less than or equal to 0.5 log 10. Interest in the conversion of manure in biogas via anaerobic digestion (AD) is growing, but questions remain about the biosafety of digestates. For a period of one year, we monitored the impact of three mesophilic agricultural biogas plants (BPs) mainly fed with pig manure (BP1, BP3) or bovine manure (BP2) on the physicochemical parameters, the composition of the microbial community and the concentration of bacteria (E. coli , enterococci, Salmonella, Campylobacter, Listeria monocytogenes, Clostridium perfringens, Clostridium botulinum and Clostridioides difficile). The BP2 digestate differed from those of the two other BPs with a higher nitrogen content, more total solids and greater abundance of Clostridia MBA03 and Disgonomonadacea. Persistence during digestion ranked from least to most, was: Campylobacter (1.6 to >2.9 log 10 reduction, according to the BP) < E. coli (1.8 to 2.2 log 10) < Salmonella (1.1 to 1.4 log 10) < enterococci (0.2 to 1.2 log 10) and C. perfringens (0.2 to 1 log 10) < L. monocytogenes (-1.2 to 1.6 log 10) < C. difficile and C. botulinum (≤0.5 log 10). No statistical link was found between the reduction in the concentration of the targeted bacteria and the physicochemical and operational parameters likely to have an effect (NH 3 , volatile fatty acids and total solids contents, hydraulic retention time, presence of co-substrates), underlining the fact that the fate of the bacteria during mesophilic digestion depends on many interacting factors. The reduction in concentrations varied significantly over the sampling period, underlining the need for longitudinal studies to estimate the impact of AD on pathogenic microorganisms. [ABSTRACT FROM AUTHOR]

• Increasing HRT to 46 days led to no detection of E. coli in digestate. • Doubling OLR reduced the Log 10 removal of enterococci and C. difficile. • Heat pretreatment of manure had no effect on the level of enterococci in digestate. This study examined the combined effect of hydraulic retention time (HRT), organic loading rate (OLR) and heat pretreatment of manure (70 °C, 1 h) on the fate of E. coli, enterococci, C. perfringens , C. difficile , and on chemical parameters (volatile fatty acids and ammonia) that may inactivate pathogens. Semi-continuous mesophilic anaerobic reactors were fed with pig manure and horse feed. The operating conditions were 2, 3, 4 COD.L−1.d−1 (OLR), 24, 35, 46 days (HRT) and use or not of a thermal pretreatment. The levels of the chemical parameters did not reach concentrations capable of inactivating the four bacteria. Anaerobic digestion led to a Log 10 removal > 3 (E. coli), 0.9–2.1 (enterococci), 0.1–0.6 (C. perfringens) and 0–1 (C. difficile). Increasing HRT only reduced the concentration of E. coli in the digestate. Increasing OLR reduced the Log 10 removal of enterococci and C. difficile. The heat pretreatment led to non-detection of E. coli in the digestate, reduced the concentration of C. perfringens by 0.8–1.3 Log 10 and increased the concentration of C. difficile by 0.04–0.7 Log 10. Enterococci, not detected in the heated manure, were present in the digestate. The distribution of genes encoding virulence factors of C. difficile (tcdA and tcdB) and C. perfringens (cpa , cpb2 and cpb) was not impacted by anaerobic digestion or by the heat pretreatment. Enterococci, C. perfringens , C. difficile were present in the digestate at relatively stable concentrations regardless of the operating conditions, indicating that even with heat pretreatment, the biosafety of digestate cannot be guaranteed in mesophilic conditions. [ABSTRACT FROM AUTHOR]

The stability of digestate organic matter is a key parameter for its use in agriculture. Here, the organic matter stability was compared between 14 post-treated digestates and the relationship between organic matter complexity and biodegradability was highlighted. Respirometric activity and CH 4 yields in batch tests showed a positive linear correlation between both types of biodegradability (R 2 = 0.8). The accessibility and complexity of organic matter were assessed using chemical extractions combined with fluorescence spectroscopy, and biodegradability was mostly anti-correlated with complexity of organic matter. Post-treatments presented a significant effect on the biodegradability and complexity of organic matter. Biodegradability was low for composted digestates which comprised slowly accessible complex molecules. Inversely, solid fractions obtained after phase separation contained a substantial part of remaining biodegradable organic matter with a significant easily accessible fraction comprising simpler molecules. Understanding the effect of post-treatment on the biodegradability of digestates should help to optimize their valorization. [ABSTRACT FROM AUTHOR]

Abstract: This study aimed to experimentally acquire evolution profiles between depth, bulk density, Free Air Space (FAS), air permeability and thermal conductivity in initial composting materials. The impact of two different moisture content, two particle size and two types of bulking agent on these four parameters was also evaluated. Bulk density and thermal conductivity both increased with depth while FAS and air permeability both decreased with it. Moreover, depth and moisture content had a significant impact on almost all the four physical parameters contrary to particle size and the type of bulking agent. [Copyright &y& Elsevier]

Signaling of all-trans retinoic acid (ATRA) through nuclear retinoid acid (RA) receptors regulates several biological functions in airway epithelial cells, eosinophils, and immune cells, yet its impact on different in vivo aspects of pulmonary allergic reaction remains elusive. We compared the effect of a treatment with liposomally encapsulated ATRA (Lipo-ATRA) in a mouse model of ovalbumin (OVA)-induced I helper (Th) 2-type responses and airway remodeling. Daily intraperitoneal injections of 10 mg/kg Lipo-ATRA, at the time of each of the 2 systemic sensitizing injections, increased OVA-induced Immunoglobulin E synthesis, bronchoalveolar lavage (BAL) eosinophilia, and accumulation of IL-10, transforming-growth factor β1, fibronectin, eotaxin/chemokine (C-C motif) ligand 11 (eotaxin/CCL11) and regulated upon activation, normal I expressed and secreted chemokine (C-C motif) ligand 5. In contrast, Lipo-ATRA, administered during each of the 4 intranasal OVA challenges, did not affect these variables. Regardless of the treatment regimen, Lipo-ATRA augmented mucin levels in BAL fluid and reduced lung total collagen content. In vitro incubation of mouse splenocytes or purified spleen cluster of differentiation (CD) 4-positive I lymphocytes, with ATRA, increased, respectively, OVA- and anti-CD 3 antibody-induced IL-4 and IL-5 production and inhibited IFNγ release. These findings demonstrate that, when given during systemic sensitization, Lipo-ATRA exacerbates allergic immune and inflammatory responses, most likely by promoting Th2 development. [ABSTRACT FROM AUTHOR]

Vaccines against the pre-erythrocytic stages of malaria hold the greatest promise as an effective intervention tool against malaria, as shown by immunization with radiation-attenuated sporozoites over four decades ago. To date, however, the development of subunit vaccines, while generating high expectations and investment, has not lived up at all to the promise. This path has been characterized by insufficient research into both identification of key defense mechanisms in humans and the discovery of better antigens, focusing rather on a technological race of how to present mainly a single antigen. The lack of success has also led, perhaps from desperation, to a revival of the live attenuated sporozoite approach, handicapped, however, by major bottlenecks in production, safety, and regulatory issues. It should now be clear that the field can no longer continue to succeed in mice and fail in the clinic. We advocate here in favor of a third option, relying on an understanding of the basis of attenuated sporozoite immunity in humans, to provide leads to the discovery of critical immunogens and the use of models with validated relevance to the human situation in order to rationalize and renew the promise of pre-erythrocytic subunit vaccines. [Copyright &y& Elsevier]

Recent studies in Africa and Asia indicate that different helminthic infections adversely affect the clinical outcome of malaria infections. This suggests that helminths can influence the acquisition of immunity against Plasmodium. Worms could constitute a confounding factor in the assessment of efficacy of malaria-control intervention, including vaccine prototypes in clinical trials. These observations have fundamental and practical consequences; if the deleterious effect of worms on malaria is confirmed, treatment of helminths would offer an affordable, strongly effective and novel means to roll back malaria. With this article, we hope to induce others to conduct similar studies in different regions. [Copyright &y& Elsevier]

Models currently occupy the crucial first step in the research flow for the development of new drugs and vaccines. Some animal models are better at reflecting the host–pathogen interaction in humans than others; this depends on the pathogen and its host specificity. Data gathered from what are often poorly adapted models provide a mosaic of sometimes contradictory information, yet there is little incentive to better delineate the relevance of models or to exploit recent advances to develop improved ones. This review reports on three particularly intractable human pathogens – Mycobacterium, Plasmodium and Schistosoma – and reflects that the extent to which these model systems mimic infection and protection processes in humans might not be sufficiently well defined. [ABSTRACT FROM AUTHOR]

• We analysed raw manure samples, mesophilic anaerobic digestates and post-digestates. • Plasmids were transferred from raw manure but not from digestates or post-digestates. • Conjugative Enterobacterales plasmids conferred resistance to various antibiotics. • Mesophilic AD processes lead to fewer conjugative Enterobacterales plasmids. • Care must be taken to avoid re-contamination during storage. Manure is a major source of antimicrobial-resistant bacteria and resistance genes carried by mobile genetic elements such as plasmids. In France, the number of on-farm biogas plants has increased significantly in recent years. Our study investigated the impact of mesophilic anaerobic digestion (AD) and the post-treatment of digestates on the fate of conjugative plasmids, along with their potential transfer of antimicrobial resistance. Samples of raw manure, digestates and post-treated digestates were collected from three on-farm biogas plants. Conjugative plasmids were captured using the Escherichia coli CV601 recipient strain and media supplemented with rifampicin and kanamycin — to which the recipient strain is resistant — and tetracycline, sulfamethoxazole, gentamicin, trimethoprim, amoxicillin, cefotaxime, ciprofloxacin or colistin. Putative transconjugants were identified and characterised by disc diffusion and whole genome sequencing. The results showed that the antimicrobial resistance genes transferred from the different matrices conferred resistance to tetracyclines, sulphonamides, trimethoprim, and/or streptomycin. Transconjugants were obtained from raw manure samples but not from digestates or post-digestates, suggesting that mesophilic AD processes may produce fewer conjugative plasmids potentially able to be transferred to Enterobacterales. [ABSTRACT FROM AUTHOR]

Drug-induced enteropathy is often associated with the therapeutic use of certain glucuronidated drugs. One such drug is mycophenolic acid (MPA), a well-established immunosuppressant of which gastrointestinal adverse effects are a major concern. The role of bacterial β-glucuronidase (β-G) from the gut microbiota in MPA-induced enteropathy has recently been discovered. Bacterial β-G hydrolyzes MPAG, the glucuronide metabolite of MPA excreted in the bile, leading to the digestive accumulation of MPA that would favor in turn these adverse events. We therefore hypothesized that taming bacterial β-G activity might reduce MPA digestive exposure and prevent its toxicity. By using a multiscale approach, we evaluated the effect of increasing concentrations of MPA on intestinal epithelial cells (Caco-2 cell line) viability, proliferation, and migration. Then, we investigated the inhibitory properties of amoxapine, a previously described bacterial β-G inhibitor, by using molecular dynamics simulations, and evaluated its efficiency in blocking MPAG hydrolysis in an Escherichia coli -based β-G activity assay. The pharmacological effect of amoxapine was evaluated in a mouse model. We observed that MPA impairs intestinal epithelial cell homeostasis. Amoxapine efficiently blocks the hydrolysis of MPAG to MPA and significantly reduces digestive exposure to MPA in mice. As a result, administration of amoxapine in MPA-treated mice significantly attenuated gastrointestinal lesions. Collectively, these results suggest that the digestive accumulation of MPA is involved in the pathophysiology of MPA-gastrointestinal adverse effects. This study provides a proof-of-concept of the therapeutic potential of bacterial β-G inhibitors in glucuronidated drug-induced enteropathy. [Display omitted] • Digestive accumulation of mycophenolic acid favors gastrointestinal adverse effects. • The bacterial β-G inhibitor, amoxapine, prevents mycophenolate-induced enteropathy. • Bacterial β-glucuronidase inhibitors as add-on therapy in drug-induced enteropathy. [ABSTRACT FROM AUTHOR]

Background Plasmodium falciparum MSP2 is a blood stage protein that is associated with protection against malaria. It was shown that the MSP2 dimorphic (D) and constant (C) regions were well recognized by immune human antibodies, and were characterized by major conserved epitopes in different endemic areas and age groups. These Abs recognized merozoite-derived proteins in WB and IFA. Here, the goal was to determine in mice the immunogenicity of the two allelic MSP2 D and C domains formulated with different adjuvants, for their possible use in future clinical studies. Method Female A/J, C3H, and ICR mice were immunized subcutaneously 3 times at 3-week interval with a mixture of allelic and conserved MSP2 long synthetic peptides formulated with different adjuvants. One week after the third injection, sera from each group were obtained and stored at −20 °C for subsequent testing. Results Both domains of the two MSP2 families are immunogenic and the fine specificity and intensity of the Ab responses are dependent on mouse strains and adjuvants. The major epitopes were restricted to the 20-mer peptide sequences comprising the last 8 aa of D and first 12 aa of C of the two allelic families and the first 20 aa of the C region, this for most strains and adjuvants. Strong immune responses were associated with GLA-SE adjuvant and its combination with other TLR agonists (CpG or GDQ) compared to alhydrogel and Montanide. Further, the elicited Abs were also capable of recognizing Plasmodium -derived MSP2 and inhibiting parasite growth in ADCI. Conclusion The data provide a valuable opportunity to evaluate in mice different adjuvant and antigen formulations of a candidate vaccine containing both MSP2 D and C fragments. The formulations with GLA-SE seem to be a promising option to be compared with the alhydrogel one in human clinical trials. [ABSTRACT FROM AUTHOR]