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Neurons have high energy needs, requiring a continuous supply of glucose from the blood. Tight regulation of glucose metabolism in response to stimuli is essential for brain physiology. Glucose metabolism and cerebral blood flow are closely coordinated during neuronal activity to maintain proper brain function. In a previous article, we have already detailed the mechanisms by which the PI3K/Akt signaling pathway is involved in the efficiency of glucose uptake by stimulating GLUT-1 action and NO-mediated vasodilation. In this article, we now clarify how the activation of BDNF helps to stimulate the IRS-1/PI3K/Akt signaling pathway and upregulates NMDA receptor activity. In short, high-frequency neuronal activity induces the secretion of BDNF, whose presence boosts this important pathway. DHA, via the PPARα-RXRα and PPARɣ-RXRα heterodimers, is involved in the critical regulation of BDNF activation. As a preferential ligand of PPARs and RXRα, DHA plays an important role in the gene expression of CREB and CPE, and it is involved in the regulation and expression of tPA, as well as the inhibition of PAI-1. BDNF boosts the IGF-1/estradiol/PI3K/Akt signaling pathway, and DHA boosts the action of BDNF.

Neurons have a high energy need, requiring a continuous supply of glucose from the blood. Tight regulation of glucose metabolism in response to stimuli is essential for brain physiology. Glucose metabolism and cerebral blood flow are closely coordinated during neuronal activity to maintain proper brain function. Glucose uptake across the blood-brain barrier is facilitated by a carrier protein: the GLUT-1 transporter. The first way the body meets urgent demand for glucose is to increase the blood flow through vasodilatory responses generated by nitric oxide. If that is insufficient, the second way is to increase the density of GLUT-1 through the translocation of this transporter from intracellular stores. The third pathway is to increase GLUT-1 synthesis by stimulating SLC2A1 (GLUT-1 gene) transcription. A tandem of two key molecules, free estradiol and DHA, is involved in this critical regulation. Their relationship is synergistic and reciprocal: free estradiol with genomic and non-genomic actions via ERα, and DHA via the PPARα-RXRα and PPARɣ-RXRα heterodimers. We highlight several original mechanisms linking two main principles (neuronal stimulation and brain energy metabolism) with the fundamental roles played by DHA and free estradiol. In particular, it has been shown that from a certain level of chronic DHA deficiency, a permanent imbalance sets in with disturbances in glucose intake and brain metabolism. This DHA deficiency is an aggravating factor in some neuropathologies.

In humans, in several biological systems, in particular the nervous system, the FADS2 gene transcribes Δ6-desaturase, which is the rate-limiting enzyme for converting α-linolenic acid into docosahexaenoic acid (an n-3 fatty acid). The peroxisome proliferator-activated receptor α (PPARα) modulates the transcription of FADS2 gene by interacting with a second transcription factor: the retinoid X receptor α (RXRα). These transcription factors take the form of a PPARα-RXRα heterodimer and are modulated by the ligands that modify their respective structures and enable them to bind to the peroxisome proliferator response element (PPRE) located in the promoter region of the FADS2 gene. Free estradiol induces the activation of PPARα via two pathways (i) transcription through genomic action mediated by an estrogen receptor; (ii) a non-genomic effect that allows for phosphorylation and activates PPARα via the ERK1/2-MAPK pathway. Phosphorylation is an on/off switch for PPARα transcription activity. Since Δ6-desaturase expression is retro-inhibited by free intracellular DHA in a dose-dependent manner, this position paper proposes an original hypothesis: if DHA simultaneously binds to both phosphorylated PPARα and RXRα, the resulting DHA-PPARαP-RXRα-DHA heterodimer represses FADS2 gene via PPRE. The retinoic acids-RARα-RXRα-DHA heterodimer would not dissociate from corepressors and would prevent coactivators from binding to FADS2. We speculate that SNPs, which are mostly located on PPRE, modulate the binding affinities of DHA-PPARαP-RXRα-DHA heterodimer to PPRE. The DHA-PPARαP-RXRα-DHA heterodimer’s greater affinity for PPRE results in a decreased production of D6D and DHA. FADS2 promoter polymorphism would increase the competition between DHA and other ligands, in accordance with their concentrations and affinities.

The process of hominization involves an increase in brain size. The development of hominids’ cognitive capital up to the emergence of Homo sapiens was due to interactive, iterative, and integrative coevolution, allowing positive selection. Although this depends on many factors, in this position paper we show three categories that stand out: gene mutations, food resources, and cognitive and behavioral stimulation. Australopithecus benefited both from the inactivation of the GULO and uricase genes and from bipedalism causing the cognitive capital of the Homo genus to develop advantageously. This evolution depended on two factors. Firstly, a triggering factor: gradual climate change. Homo started to regularly consume meat in addition to plants and insects. Secondly, a stimulating factor: mutations in the FADS2 gene, which encodes Δ6-desaturase; a key enzyme for the synthesis of DHA and sapienic acid. The polymorphism of this gene appears to have been essential in allowing the Homo genus to adapt to its food, and for its evolution. It provides an undeniable advantage in terms of the productivity of fat synthesis (DHA), and may partly explain positive selection. With the advent of cooking and new mutations producing even more FADS2, the brain reached its maximum size in Homo neanderthalensis, in a food ecosystem that provided favorable quantities of α-Linolenic acid and DHA. However, the Würm glaciation upset this equilibrium, revealing its fragility as regards to the brain and fertility. Homo sapiens, benefiting from new variants of the FADS2 gene, were able to adapt to this harsh environment, whereas Neanderthal man was unable to do so and became extinct.

Clostridium botulinum is a Gram -positive, strict anaerobic, rod -shaped, spore -forming, SOD -positive and catalase -negative bacterium. Its antioxidant defenses are not suited to chronic oxidative stress. H₂O₂ and reactive oxygen species have deleterious effects on C. botulinum. Spore germination is one of the key steps in its development. However, the mechanisms that trigger this germination have yet to be described. To manage C. botulinum growth, it is essential to understand the mechanisms that underlie the germination process. In this article, a series of complementary cascade reactions with water -dissolved CO₂ as an initiating germinant, and bicarbonate is suggested. It seems clear that ATP production is achieved through the use of various anaplerotic reactions with dissolved CO₂ as the carbon source. In addition to the production of oxaloacetate, an intermediate metabolite pyruvate would also be synthesized. Pyruvate would initiate the second phase of germination by producing hydrogen, which is a powerful reducing agent, via two enzymes (pyruvate -ferredoxin oxidoreductase and ferredoxin hydrogenase). These conditions would activate proteolytic enzymes and would reduce and would break the disulfide bridges of the proteins that make up the spore coats, thereby opening them. Thus, the phosphoenolpyruvate -pyruvate -acetyl -CoA pathway, in the presence of CO₂, would play a major role in the germination of spores of C. botulinum., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

By-products like CO₂ and organic acids, produced during Clostridium botulinum growth, appear to inhibit its development and reduce ATP production. A decrease in ATP production creates an imbalance in the ATP/GTP ratio. GTP activates CodY, which regulates BoNT expression. This toxin is released into the extracellular medium. Its light chains act as a specific endopeptidase, targeting SNARE proteins. The specific amino acids released enter the cells and are metabolized by the Stickland reaction, resulting in the synthesis of ATP. This ATP might then be used by histidine kinases to activate Spo0A, the main regulator initiating sporulation, through phosphorylation., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

In the early stages of sporadic Alzheimer's disease (SAD), there is a strong correlation between memory impairment and cortical levels of soluble amyloid-β peptide oligomers (Aβ). It has become clear that Aβ disrupt glutamatergic synaptic function, which can in turn lead to the characteristic cognitive deficits of SAD, but the actual pathways are still not well understood. This opinion article describes the pathogenic mechanisms underlying cerebral amyloidosis. These mechanisms are dependent on the amyloid precursor protein and concern the synthesis of Aβ peptides with competition between the non-amyloidogenic pathway and the amyloidogenic pathway (i.e. a competition between the ADAM10 and BACE1 enzymes), on the one hand, and the various processes of Aβ residue clearance, on the other hand. This clearance mobilizes both endopeptidases (NEP, and IDE) and removal transporters across the blood-brain barrier (LRP1, ABCB1, and RAGE). Lipidated ApoE also plays a major role in all processes. The disturbance of these pathways induces an accumulation of Aβ. The description of the mechanisms reveals two key molecules in particular: (i) free estradiol, which has genomic and non-genomic action, and (ii) free DHA as a preferential ligand of PPARα-RXRα and PPARɣ-RXRα heterodimers. DHA and free estradiol are also self-regulating, and act in synergy. When a certain level of chronic DHA and free estradiol deficiency is reached, a permanent imbalance is established in the central nervous system. The consequences of these deficits are revealed in particular by the presence of Aβ peptide deposits, as well as other markers of the etiology of SAD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

We investigated the impact of increased alpha-linolenic acid (ALA) dietary levels on its plasma bioavailability and its bioconversion in n -3 long chain poly unsaturated fatty acids during a 60-d kinetics and the oxidative stress potentially associated. Rats were submitted to a normolipidic diet providing 0, 3, 10 and 24% ALA of dietary lipids for 0, 15, 30 and 60 days. The lipid peroxidation and oxidative stress (nitric oxide (NO) contents and catalase (CAT), superoxide dismutase (SOD), gluthation peroxidase (GPx) activities) were studied in the liver and plasma. When the diet was deprived in n -3 PUFAs, ALA, (eicosanoic acid) EPA and docosahexaenoic acid (DHA) levels decreased in all lipid fractions of plasma and in red blood cell (RBC) lipids. The addition of ALA in the diet linearly improves its bioavailability and its bioconversion in EPA ( R ²=0.98). By providing 10 to 24% ALA in dietary lipids (LA/ALA, 1·6 and 5·5 respectively), ALA and EPA were more broadly packaged in all lipid fractions (triglyceride (TAG), cholesterol ester (CE) and free fatty acids (FFA)) of plasma from 15 to 30 days timeframe. Only 3% ALA was sufficient to promote the maximal bioconversion of ALA in DHA in phospholipid (PL) and TAG fractions. Additionally, the improvement of ALA bioconversion in EPA and DHA did not impact the oxidative stress markers and limiting lipid peroxidation. To conclude, this study demonstrated that in rat, 10% ALA in the lipid diet for 15-30 days promotes its bioavailability and its bioconversion and allowed the greatest levels in plasma and RBCs.

Introduction: Episode-based bundled payment model is actually opposing to fee-for-service model, intending to incentivize coordinated care. The aims of these study were to determine episode-based costs for surgery in early breast cancer patients and to propose a payment model., Methods: OPTISOINS01 was a multicenter prospective study including early breast cancer patients from diagnosis to one-year follow up. Direct medical costs, quality and patient reported outcomes were collected., Results: Data from 604 patients were analyzed. Episode-based costs for surgery were higher in case of: planned radical surgery (OR=9,47 ; IC95 % [3,49-28,01]; P<0,001), hospitalization during more than one night (OR=6,73; IC95% [2,59-17,46]; P<0,001), home hospitalization (OR=11,07 ; IC95 % [3,01-173][3,01-54][3,01-543][3,01-54,33]; P<0,001) and re-hospitalization (OR=25,71 ; IC95 % [9,24-89,17; P<0,001). The average cost was 5 268 € [2 947-18 461] when a lumpectomy was planned and 7408 € [4 222-22 565] in case of radical mastectomy. Bootstrap method was applied for internal validation of the cost model showing the reliability of the model with an area under the curve of 0,83 (95 % CI [0,80-0,86]). Care quality and patient reported outcomes were not related to the costs., Discussion: This is the first report of episode-based costs for breast cancer surgery. An external validation will be necessary to validate our payment model., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Most of the defective/non-infectious enteric phages and viruses that end up in wastewater originate in human feces. Some of the causes of this high level of inactivity at the host stage are unknown. There is a significant gap between how enteric phages are environmentally transmitted and how we might design molecular tools that would only detect infectious ones. Thus, there is a need to explain the low proportion of infectious viral particles once replicated. By analyzing lysis plaque content, we were able to confirm that, under aerobic conditions, Escherichia coli produce low numbers of infectious MS2 phages (I) than the total number of phages indicated by the genome copies (G) with an I/G ratio of around 2%. Anaerobic conditions of replication and ROS inhibition increase the I/G ratio to 8 and 25%, respectively. These data cannot only be explained by variations in the total numbers of MS2 phages produced or in the metabolism of E. coli . We therefore suggest that oxidative damage impacts the molecular replication and assembly of MS2 phages.

Competing Interests: There are no financial or other issues that might lead to conflict of interest.

Human noroviruses (HuNoVs) are one of the leading causes of acute gastroenteritis worldwide. HuNoVs are frequently detected in water and foodstuffs. Free chlorine and peroxynitrite (ONOO - ) are two oxidants commonly encountered by HuNoVs in humans or in the environment during their natural life cycle. In this study, we defined the effects of these two oxidants on GII.4 HuNoVs and GII.4 virus-like particles (VLPs). The impact on the capsid structure, the major capsid protein VP1 and the ability of the viral capsid to bind to histo-blood group antigens (HBGAs) following oxidative treatments were analyzed. HBGAs are attachment factors that promote HuNoV infection in human hosts. Overall, our results indicate that free chlorine acts on regions involved in the stabilization of VP1 dimers in VLPs and affects their ability to bind to HBGAs. These effects were confirmed in purified HuNoVs. Some VP1 cross-links also take place after free chlorine treatment, albeit to a lesser extent. Not only ONOO - mainly produced VP1 cross-links but can also dissociate VLPs depending on the concentration applied. Nevertheless, ONOO - has less effect on HuNoV particles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chassaing, Bastin, Robin, Majou, Belliot, de Rougemont, Boudaud and Gantzer.)

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Histo-Blood Groups Antigens (HBGAs) have been described as attachment factors, promoting HuNoV infection. However, their role has not yet been elucidated. This study aims to evaluate the ability of HBGAs to protect HuNoVs against various factors naturally found in the human digestive system. The effects of acid pH and proteolytic enzymes (pepsin, trypsin, and chymotrypsin) on GII.4 virus-like particles (VLPs) and GII.4 HuNoVs were studied, both during interactions and non-interaction with HBGAs. The results showed that GII.4 VLPs and GII.4 HuNoVs behaved differently following the treatments. GII.4 VLPs were disrupted at a pH of less than 2.0 and in the presence of proteolytic enzymes (1,500 units/mL pepsin, 100 mg/mL trypsin, and 100 mg/mL chymotrypsin). VLPs were also partially damaged by lower concentrations of trypsin and chymotrypsin (0.1 mg/mL). Conversely, the capsids of GII.4 HuNoVs were not compromised by such treatments, since their genomes were not accessible to RNase. HBGAs were found to offer GII.4 VLPs no protection against an acid pH or proteolytic enzymes.

Pathogenic enteric viruses and bacteriophages such as Qβ and MS2 are transmitted through the fecal-oral route. However, oxidants such as peroxynitrite (ONOOH) and hypochlorous acid (HClO) can prevent new infection by inactivating infectious viruses. Their virucidal effect is well recognized, and yet predicting the effects of oxidants on viruses is currently impossible because the detailed mechanisms of viral inactivation remain unclear. Our data show that ONOOH and HClO cross-linked the capsid proteins and RNA genomes of Qβ and MS2 phages. Consistently, the capsids appeared intact by transmission electron microscopy (TEM) even when 99% of the phages were inactivated by oxidation. Moreover, a precise molecular study of the capsid proteins shows that ONOOH and HClO preferentially targeted capsid protein regions containing the oxidant-sensitive amino acid C, Y, or W. Interestingly, the interaction of these amino acids was a crucial parameter defining whether they would be modified by the addition of O, Cl, or NO 2 or whether it induced the loss of the protein region detected by mass spectrometry, together suggesting potential sites for cross-link formation. Together, these data show that HClO and ONOOH consistently target oxidant-sensitive amino acids regardless of the structural organization of Qβ and MS2, even though the phenotypes change as a function of the interaction with adjacent proteins/RNA. These data also indicate a potential novel mechanism of viral inactivation in which cross-linking may impair infectivity., (Copyright © 2020 Bastin, Loison, Vernex-Loset, Dupire, Challant, Majou, Boudaud, Krier and Gantzer.)

Noroviruses (NoV) are responsible for many shellfish outbreaks. Purification processes may be applied to oysters before marketing to decrease potential fecal pollution. This step is rapidly highly effective in reducing Escherichia coli ; nevertheless, the elimination of virus genomes has been described to be much slower. It is therefore important to identify (i) the purification conditions that optimize virus removal and (ii) the mechanism involved. To this end, the effects of oyster stress, nutrients, and the presence of a potential competitor to NoV adhesion during purification were investigated using naturally contaminated oysters. Concentrations of NoV (genomes) and of the viral indicator F-specific RNA bacteriophage (FRNAPH; genomes and infectious particles) were regularly monitored. No significant differences were observed under the test conditions. The decrease kinetics of both virus genomes were similar, again showing the potential of FRNAPH as an indicator of NoV behavior during purification. The T 90 (time to reduce 90% of the initial titer) values were 47.8 days for the genogroup I NoV genome, 26.7 days for the genogroup II NoV genome, and 43.9 days for the FRNAPH-II genome. Conversely, monitoring of the viral genomes could not be used to determine the behavior of infectious viruses because the T 90 values were more than two times lower for infectious FRNAPH (20.6 days) compared to their genomes (43.9 days). Finally, this study highlighted that viruses are primarily inactivated in oysters rather than released in the water during purification processes. IMPORTANCE This study provides new data about the behavior of viruses in oysters under purification processes and about their elimination mechanism. First, a high correlation has been observed between F-specific RNA bacteriophages of subgroup II (FRNAPH-II) and norovirus (NoV) in oysters impacted by fecal contamination when both are detected using molecular approaches. Second, when using reverse transcription-quantitative PCR and culture to detect FRNAPH-II genomes and infectious FRNAPH in oysters, respectively, it appears that genome detection provides limited information about the presence of infectious particles. The comparison of both genomes and infectious particles highlights that the main mechanism of virus elimination in oysters is inactivation. Finally, this study shows that none of the conditions tested modify virus removal., (Copyright © 2020 American Society for Microbiology.)

Human noroviruses (HuNoVs) are the leading cause of viral foodborne outbreaks worldwide. To date, no available methods can be routinely used to detect infectious HuNoVs in foodstuffs. HuNoVs recognize Histo-Blood Group Antigens (HBGAs) through the binding pocket (BP) of capsid protein VP1, which promotes infection in the host cell. In this context, the suitability of human HBGA-binding assays to evaluate the BP integrity of HuNoVs was studied on GII.4 virus-like particles (VLPs) and GII.4 HuNoVs during natural ageing at 20 °C and heat treatments. Our results demonstrate that this approach may reduce the over-estimation of potential infectious HuNoVs resulting from solely using the genome detection, even though some limitations have been identified. The specificity of HBGA-binding to the BP is clearly dependent on the HGBA type (as previously evidenced) and the ionic strength of the media without disturbing such interactions. This study also provides new arguments regarding the ability of VLPs to mimic HuNoV behavior during inactivation treatments. The BP stability of VLPs was at least 4.3 fold lower than that of HuNoVs at 20 °C, whereas capsids of both particles were disrupted at 72 °C. Thus, VLPs are relevant surrogates of HuNoVs for inactivation treatments inducing significant changes in the capsid structure.

Toxoplasma gondii is a ubiquitous foodborne protozoan that can infect humans at low dose and displays different prevalences among countries in the world. Ingestion of food or water contaminated with small amounts of T. gondii oocysts may result in human infection. However, there are no regulations for monitoring oocysts in food, mainly because of a lack of standardized methods to detect them. The objectives of this study were (i) to develop a reliable method, applicable in biomonitoring, for the rapid detection of infectious oocysts by cell culture of their sporocysts combined with quantitative PCR (sporocyst-CC-qPCR) and (ii) to adapt this method to blue and zebra mussels experimentally contaminated by oocysts with the objective to use these organisms as sentinels of aquatic environments. Combining mechanical treatment and bead beating leads to the release of 84% ± 14% of free sporocysts. The sporocyst-CC-qPCR detected fewer than ten infectious oocysts in water within 4 days (1 day of contact and 3 days of cell culture) compared to detection after 4 weeks by mouse bioassay. For both mussel matrices, oocysts were prepurified using a 30% Percoll gradient and treated with sodium hypochlorite before cell culture of their sporocysts. This assay was able to detect as few as ten infective oocysts. This sporocyst-based CC-qPCR appears to be a good alternative to mouse bioassay for monitoring infectious T. gondii oocysts directly in water and also using biological sentinel mussel species. This method offers a new perspective to assess the environmental risk for human health associated with this parasite. IMPORTANCE The ubiquitous protozoan Toxoplasma gondii is the subject of renewed interest due to the spread of oocysts in water and food causing endemic and epidemic outbreaks of toxoplasmosis in humans and animals worldwide. Displaying a sensitivity close to animal models, cell culture represents a real alternative to assess the infectivity of oocysts in water and in biological sentinel mussels. This method opens interesting perspectives for evaluating human exposure to infectious T. gondii oocysts in the environment, where oocyst amounts are considered to be very small., (Copyright © 2019 American Society for Microbiology.)

We report the resection of a recurrent epithelioid trophoblastic tumor by laparoscopic laterally extended endopelvic resection (LEER). The LEER technique was developed to resect en bloc multiple visceral compartments involving the lateral pelvic wall with negative margins for local control of advanced and recurrent malignancies. Described by Höckel, this procedure is usually performed by a midline laparotomy. Our patient had undergone prior laparotomic surgery including hysterectomy, partial bladder resection, and a right ureteral reimplantation for an epithelioid trophoblastic tumor without adjuvant treatment. She presented a recurrent tumor infiltrating the bladder, the ureter, and the right pelvic wall as well as the internal and external iliac vessels. A vascular surgeon first performed a femorofemoral bypass by bilateral groin incisions with a subcutaneous tunnel. The surgery was then exclusively performed by laparoscopy using the LEER technique including resection of both external and internal iliac vessels and the pelvic wall through the lateral pelvic muscles and iterative bladder resection associated with a ureteral reimplantation using the psoas hitch bladder technique. The patient experienced Clavien-Dindo classification grade II postoperative complications. Histology showed a margin-free resection (R0)., (Copyright © 2019. Published by Elsevier Inc.)

For cured meat products, nitrite is recognized for its antimicrobial effects against pathogenic bacteria, even though the specific inhibitory mechanisms are not well known. Nitrite contributes to oxidative stress by being the precursor of peroxynitrite (ONOO - ), which is the major strong oxidant. Thus, bacterial stress (highly pH-very low partial pressure of oxygen-dependent) is enhanced by the nitrate-nitrite-peroxynitrite system which is also highly pH- and low partial pressure of oxygen-dependent. Nitrite is a hurdle technology which effectiveness depends on several other hurdle technologies including sodium chloride (accelerating the autoxidation of oxymyoglobin and promote peroxynitrite formation), ascorbate (increasing ONOO - synthesis), and Aw. In this environment, certain species are more resistant than others to acidic, oxidative, and nitrative stresses. The most resistant are gram-negative aerobic/facultative anaerobic bacteria (Escherichia coli, Salmonella), and the most fragile are gram-positive anaerobic bacteria (Clostridium botulinum). This position review highlights the major chemical mechanisms involved, the active molecules and their actions on bacterial metabolisms in the meat ecosystem., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Qβ phages infect Escherichia coli in the human gut by recognizing F-pili as receptors. Infection therefore occurs under reducing conditions induced by physiological agents (e.g. glutathione) or the intestinal bacterial flora. After excretion in the environment, phage particles are exposed to oxidizing conditions and sometimes disinfection. If inactivation does not occur, the phage may infect new hosts in the human gut through the oral route. During such a life cycle, we demonstrated that, outside the human gut, cysteines of the major protein capsid of Qβ phage form disulfide bonds. Disinfection with NaClO does not allow overoxidation to occur. Such oxidation induces inactivation rather by irreversible damage to the minor proteins. In the presence of glutathione, most disulfide bonds are reduced, which slightly increases the capacity of the phage to infect E. coli in vitro Such reduction is reversible and barely alters infectivity of the phage. Reduction of all disulfide bonds by dithiothreitol leads to complete capsid destabilization. These data provide new insights into how the phages are impacted by oxidizing-reducing conditions outside their host cell and raises the possibility of the intervention of the redox during life cycle of the phage., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)