Defense System Research Articles

The vibriophage-encoded inhibitor OrbA abrogates BREX-mediated defense through the ATPase BrxC.

Bacteria and phages are locked in a co-evolutionary arms race where each entity evolves mechanisms to restrict the proliferation of the other. Phage-encoded defense inhibitors have proven powerful tools to interrogate how defense systems function. A relatively common defense system is BREX (bacteriophage exclusion); however, how BREX functions to restrict phage infection remains poorly understood. A BREX system encoded by the sulfamethoxazole and trimethoprim (SXT) integrative and conjugative element, VchInd5, was recently identified in Vibrio cholerae, the causative agent of the diarrheal disease cholera. The lytic phage ICP1 (International Centre for Diarrhoeal Disease Research, Bangladesh cholera phage 1) that co-circulates with V. cholerae encodes the BREX-inhibitor OrbA, but how OrbA inhibits BREX is unclear. Here, we determine that OrbA inhibits BREX using a unique mechanism from known BREX inhibitors by directly binding to the BREX component BrxC. BrxC has a functional ATPase domain that, when mutated, not only disrupts BrxC function but also alters how BrxC multimerizes. Furthermore, we find that OrbA binding disrupts BrxC-BrxC interactions. We determine that OrbA cannot bind BrxC encoded by the distantly related BREX system encoded by the aSXT VchBan9, and thus fails to inhibit this BREX system that also circulates in epidemic V. cholerae. Lastly, we find that homologs of the VchInd5 BrxC are more diverse than the homologs of the VchBan9 BrxC. These data provide new insight into the function of the BrxC ATPase and highlight how phage-encoded inhibitors can disrupt phage defense systems using different mechanisms.IMPORTANCEWith renewed interest in phage therapy to combat antibiotic-resistant pathogens, understanding the mechanisms bacteria use to defend themselves against phages and the counter-strategies phages evolve to inhibit defenses is paramount. Bacteriophage exclusion (BREX) is a common defense system with few known inhibitors. Here, we probe how the vibriophage-encoded inhibitor OrbA inhibits the BREX system of Vibrio cholerae, the causative agent of the diarrheal disease cholera. By interrogating OrbA function, we have begun to understand the importance and function of a BREX component. Our results demonstrate the importance of identifying inhibitors against defense systems, as they are powerful tools for dissecting defense activity and can inform strategies to increase the efficacy of some phage therapies.

Complete genomes of Asgard archaea reveal diverse integrated and mobile genetic elements.

Asgard archaea are of great interest as the progenitors of Eukaryotes, but little is known about the mobile genetic elements (MGEs) that may shape their ongoing evolution. Here, we describe MGEs that replicate in Atabeyarchaeia, a wetland Asgard archaea lineage represented by two complete genomes. We used soil depth-resolved population metagenomic data sets to track 18 MGEs for which genome structures were defined and precise chromosome integration sites could be identified for confident host linkage. Additionally, we identified a complete 20.67 kbp circular plasmid and two family-level groups of viruses linked to Atabeyarchaeia, via CRISPR spacer targeting. Closely related 40 kbp viruses possess a hypervariable genomic region encoding combinations of specific genes for small cysteine-rich proteins structurally similar to restriction-homing endonucleases. One 10.9 kbp integrative conjugative element (ICE) integrates genomically into the Atabeyarchaeum deiterrae-1 chromosome and has a 2.5 kbp circularizable element integrated within it. The 10.9 kbp ICE encodes an expressed Type IIG restriction-modification system with a sequence specificity matching an active methylation motif identified by Pacific Biosciences (PacBio) high-accuracy long-read (HiFi) metagenomic sequencing. Restriction-modification of Atabeyarchaeia differs from that of another coexisting Asgard archaea, Freyarchaeia, which has few identified MGEs but possesses diverse defense mechanisms, including DISARM and Hachiman, not found in Atabeyarchaeia. Overall, defense systems and methylation mechanisms of Asgard archaea likely modulate their interactions with MGEs, and integration/excision and copy number variation of MGEs in turn enable host genetic versatility.

Regulation of Physiological and Biochemical Mechanisms Related to Water Stress Tolerance in Barley and Improvement of Growth and Productivity Using Salicylic Acid and Chitosan

The present investigation aimed to assess the impacts of three Salicylic Acid (SA) concentrations (T2=100, T3=200, T4=300ppm), three Chitosan concentrations (T5=150, T6=225, T7=300ppm) and T8= Salicylic Acid (100 ppm) with Chitosan (150 ppm) mixture in comparison to control treatment (T1) on two barley cultivars Giza126 and Giza 134 under rainfed conditions. Some vegetative and yield traits were recorded, plant height, spike length, number of gains spike-1, number of spikes/m2, 1000 grain weight, biological and grain yield. A split plot design was performed with three replications. The field experiment was conducted in the northern west coast region of Egypt (Marsa Matruh government) under the rainfed condi­tions during 2019/2020 and 2020/2021 growing seasons. The results showed a direct relationship between increased foliar application and increased yield attributes. Results indicated that Giza 126 cultivar as affected by T4 showed the most desirable values for grains spikes-1 in first season, spikes/m2, biological yield and grain yield during the first and second seasons respectively. In addition, barley cultivar Giza 126 as affected by T3 showed the highest values for grains spikes-1 in second season. On the other hand, barley cultivar Giza 134 as affected by T4 showed the highest values for plant height, spike length and 1000-grain weight in first and second seasons respectively. From results, it can be concluded that the Salicylic Acid (SA) concentration 300 ppm is recommendable for improving the productivity of barley under rainfed conditions of Egypt. To study the potential role of SA and Chitosan on water stress tolerance mechanisms some biochemical and physiological parameters were recorded. Application of SA and Chitosan decreased significantly Reactive Oxygen Species (ROS) measuring by determined the concentrations of MDA and H2O2 especially SA with concentrations 300 ppm (T4). For osmolytes (proline, SSC and SPC), all treatments using SA and Chitosan induced significant increase in osmolytes content compared with control under water stress only in the two studied barley genotypes, except for treatment with Chitosan 225 and 300 ppm in Giza 126 for proline content. Similar results were recorded for antioxidant enzymes activity (CAT, POX and PPO) which showed up-regulation for all treatments compared with control under water stress for the two studied genotypes. On contrast, APX antioxidant enzyme recorded the highest activity in control treatment under water stress only. In general, for all studied treatments comparing with control, application of SA300 ppm and the mixture between SA100 and Chitosan150 ppm were the best treatment for induction of up and down regulation of biochemical and physiological component in the barley cells which is known as defense system against water stress damage.

Pipolins are bimodular platforms that maintain a reservoir of defense systems exchangeable with various bacterial genetic mobile elements.

Defense genes gather in diverse types of genomic islands in bacteria and provide immunity against viruses and other genetic mobile elements. Here, we disclose pipolins, previously found in diverse bacterial phyla and encoding a primer-independent PolB, as a new category of widespread defense islands. The analysis of the occurrence and structure of pipolins revealed that they are commonly integrative elements flanked by direct repeats in Gammaproteobacteria genomes, mainly Escherichia, Vibrio or Aeromonas, often taking up known mobile elements integration hotspots. Remarkably, integrase dynamics correlates with alternative integration spots and enables diverse lifestyles, from integrative to mobilizable and plasmid pipolins, such as in members of the genera Limosilactobacillus, Pseudosulfitobacter or Staphylococcus. Pipolins harbor a minimal core and a large cargo module enriched for defense factors. In addition, analysis of the weighted gene repertoire relatedness revealed that many of these defense factors are actively exchanged with other mobile elements. These findings indicate pipolins and, potentially other defense islands, act as orthogonal reservoirs of defense genes, potentially transferable to immune autonomous MGEs, suggesting complementary exchange mechanisms for defense genes in bacterial populations.

Neurobehavioral and bioaccumulative toxicity in adult in-vivo zebrafish model due to prolonged cadmium exposure in the presence of ketoprofen.

Increasing industrial activity causes the release of chemical compounds into aquatic habitats, including toxic heavy metals like cadmium and medications like ketoprofen, posing considerable ecological concerns. Although previous studies have shown that cadmium and ketoprofen individually cause cognitive impairment, there is a lack of information on the combined neurological effects of the two substances. We investigated the neurological consequences of persistent cadmium exposure in the presence of ketoprofen on adult zebrafish, providing an essential model for understanding cumulative impacts on vertebrate organisms. Behavioral assessments, bioaccumulation rates, biochemical studies, and histopathological exams were conducted over 42 days in authentic environmental settings. The results of our study show that cadmium (10 µg/L) and ketoprofen (10 and 100 µg/L) at environmentally relevant concentrations had a significant impact on locomotor activity, social interactions, and cognitive responses, indicating cumulative neurotoxicity in co-exposure groups compared to single pollutant groups. Biochemical tests show disturbances in antioxidant defense systems, while histological examinations reveal structural changes in zebrafish brain regions. Ketoprofen influences cadmium accumulation in the brain, underscoring the importance of conducting complete evaluations to understand the intricate interactions between environmental pollutants. This study improves our understanding of the complex interactions between heavy metals and medications, stressing the need to consider combined exposure when assessing the neurological effects on vertebrate models.

Foliar application of esculin and digitoxin improve the yield quality of salt-stressed flax by improving the antioxidant defense system

BackgroundSecondary metabolites of several plants, including esculin and digitoxin, which are cardiac glycosides, were previously employed for their therapeutic effects. The current study aims to investigate the functions of the main Na+ /K+ transport inhibitor digitoxin and the antioxidant esculin for enhancing flax plant growth and production under salinity.MethodologyFlax plants were irrigated with distilled water supplemented with 0.0 and 5000 mg/L salt solution starting from 15 DAS from sowing. Then exogenous treatment with digitoxin and esculin with 50 mg L− 1 and 100 mg L− 1 were used for this work.ResultsAccording to the results of this work, foliar spraying of esculin or digitoxin increased the salinity tolerance of flax plants.The foliar application of either esculin or digitoxin induced an elevation in the contents of photosynthetic pigments, osmolytes including soluble sugar and proline as well as the total phenols in salt-stressed flax plants. Moreover, esculin and digitoxin in particular counteract oxidative stress by increasing the activity of antioxidant enzymes including superoxide dismutase, catalase, peroxidase, phenylalanine ammonia-lyase, and tyrosine ammonia lyase, leading to a decrease in reactive oxygen species and lipid peroxidation levels and electrolyte leakage. The efficiency of esculin and digitoxin to sustain ion homeostasis by inhibiting Na+ absorption and increasing potassium, calcium, and phosphorus in flax plants may be the reason for their protective actions towards salinity.As a consequence, esculin and digitoxin increased yield quantity and quality as shown by increases in all investigated yield criteriaas shoot height, root length, their fresh and dry weights as well asseed yield/plant (g), and 1000 seeds weight, especially those that improved the desired oil properties.ConclusionIn conclusion, this study concluded that digitoxin was more effective in inhibiting Na+ build-up and increasing flax salinity tolerance, particularly at the high investigated dose as compared to esculin. In this study, we reported the recent findings of exogenousapplication of either digitoxin or esculin glycosides which are new investigated salt alleviators never used before for improving the salt tolerance in flax plants.

ESI MS Studies Of T. brucei Trypanothione Reductase And Its Reactions With Selected Metal Compounds

Trypanothione reductase from Trypanosoma brucei (TbTR) is a key enzyme of the parasite responsible for human African trypanosomiasis. TbTR catalyzes the reduction of trypanothione, an antioxidant dithiol that protects trypanosomatid parasites from oxidative stress induced by the mammalian host as a defense system. TbTR is considered an attractive target for the development of novel anti‐parasitic drugs because it is essential for parasite survival and has no close homologues in humans. Previous studies have shown that metal compounds can act as potent inhibitors of trypanothione reductase and of related enzymes and may be considered for disease treatment. To better understand the molecular basis of such inhibition, we report the study of the interactions of a small group of metal compounds with TbTR, analyzed by ESI MS measurements. This technique allows direct visualization of the enzyme in solution and the detection and characterization of the metal binding process. Accordingly, TbTR was reacted with a panel of metal compounds including thimerosal, auranofin, its halogen analogues, and bismuth acetate. ESI MS results provide a detailed description of the interactions taking place for each metal compound tested. The implications of these results for the development of novel metal‐based compounds as potential anti‐trypanosomal agents are discussed.

Intragenomic conflicts with plasmids and chromosomal mobile genetic elements drive the evolution of natural transformation within species.

Natural transformation is the only mechanism of genetic exchange controlled by the recipient bacteria. We quantified its rates in 786 clinical strains of the human pathogens Legionella pneumophila (Lp) and 496 clinical and environmental strains of Acinetobacter baumannii (Ab). The analysis of transformation rates in the light of phylogeny revealed they evolve by a mixture of frequent small changes and a few large quick jumps across 6 orders of magnitude. In standard conditions close to half of the strains of Lp and a more than a third in Ab are below the detection limit and thus presumably non-transformable. Ab environmental strains tend to have higher transformation rates than the clinical ones. Transitions to non-transformability were frequent and usually recent, suggesting that they are deleterious and subsequently purged by natural selection. Accordingly, we find that transformation decreases genetic linkage in both species, which might accelerate adaptation. Intragenomic conflicts with chromosomal mobile genetic elements (MGEs) and plasmids could explain these transitions and a GWAS confirmed systematic negative associations between transformation and MGEs: plasmids and other conjugative elements in Lp, prophages in Ab, and transposable elements in both. In accordance with the hypothesis of modulation of transformation rates by genetic conflicts, transformable strains have fewer MGEs in both species and some MGEs inactivate genes implicated in the transformation with heterologous DNA (in Ab). Innate defense systems against MGEs are associated with lower transformation rates, especially restriction-modification systems. In contrast, CRISPR-Cas systems are associated with higher transformation rates suggesting that adaptive defense systems may facilitate cell protection from MGEs while preserving genetic exchanges by natural transformation. Ab and Lp have different lifestyles, gene repertoires, and population structure. Nevertheless, they exhibit similar trends in terms of variation of transformation rates and its determinants, suggesting that genetic conflicts could drive the evolution of natural transformation in many bacteria.

Proline metabolism is essential for alkaline adaptation of Nile tilapia (Oreochromis niloticus)

BackgroundSaline-alkaline water aquaculture has become a key way to mitigate the reduction of freshwater aquaculture space and meet the increasing global demand for aquatic products. To enhance the comprehensive utilization capability of saline-alkaline water, it is necessary to understand the regulatory mechanisms of aquatic animals coping with saline-alkaline water. In this study, our objective was to elucidate the function of proline metabolism in the alkaline adaptation of Nile tilapia (Oreochromis niloticus).ResultsExpose Nile tilapia to alkaline water of different alkalinity for 2 weeks to observe changes in its growth performance and proline metabolism. Meanwhile, to further clarify the role of proline metabolism, RNA interference experiments were conducted to disrupt the normal operation of proline metabolic axis by knocking down pycr (pyrroline-5-carboxylate reductases), the final rate-limiting enzyme in proline synthesis. The results showed that both the synthesis and degradation of proline were enhanced under carbonate alkalinity stress, and the environmental alkalinity impaired the growth performance of tilapia, and the higher the alkalinity, the greater the impairment. Moreover, environmental alkalinity caused oxidative stress in tilapia, enhanced ion transport, ammonia metabolism, and altered the intensity and form of energy metabolism in tilapia. When the expression level of the pycr gene decreased, the proline metabolism could not operate normally, and the ion transport, antioxidant defense system, and energy metabolism were severely damaged, ultimately leading to liver damage and a decreased survival rate of tilapia under alkalinity stress.ConclusionsThe results indicated that proline metabolism plays an important role in the alkaline adaptation of Nile tilapia and is a key regulatory process in various biochemical and physiological processes.

Using CRISPR-Cas9 genome editing to enhance disease resistance in banana

Abstract Bananas and plantains ( Musa spp.) are leading global fruit crops, cultivated in over 150 countries and several island nations and serving as fruit and staple food in tropical and subtropical regions. Notwithstanding their economic importance, banana production is hindered by pests, diseases, and climatic challenges, resulting in significant yield gaps and post-harvest losses. Conventional breeding methods are time-consuming and labor-intensive due to the 15–18 months long life cycle and seedless nature of the edible crop, while transgenic approaches face regulatory, public acceptance, and sociopolitical hurdles. The advent of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-Cas9) technology offers a precise, targeted, and efficient tool for genetic mutation derived from the bacterial antiviral defense system. Researchers are exploring CRISPR-Cas9 to develop banana varieties resistant to diseases and pests, exhibit higher yields, and possess enhanced nutritional profiles. The well-annotated complete banana genome, combined with advanced regeneration and transformation systems, facilitates the application of CRISPR-Cas9 technology. This innovative approach promises to create superior banana cultivars that benefit consumers and farmers, addressing critical challenges in banana production and contributing to global food security. This review article discusses the challenges in banana production, including biotic and abiotic constraints, and explores recent advancements in genome editing.

Effect of a loss of the mda5/ifih1 gene on the antiviral resistance in a Chinook salmon Oncorhynchus tshawytscha cell line.

Cells are equipped with intracellular RIG-like Receptors (RLRs) detecting double stranded (ds)RNA, a molecule with Pathogen-Associated Molecular Pattern (PAMPs) generated during the life cycle of many viruses. Melanoma Differentiation-Associated protein 5 (MDA5), a helicase enzyme member of the RLRs encoded by the ifih1 gene, binds to long dsRNA molecules during a viral infection and initiates production of type I interferon (IFN1) which orchestrates the antiviral response. In order to understand the contribution of MDA5 to viral resistance in fish cells, we have isolated a clonal Chinook salmon Oncorhynchus tshawytscha epithelial-like cell line invalidated for the ifih1 gene by CRISPR/Cas9 genome editing. We demonstrated that IFN1 induction is impaired in this cell line after infection with the Snakehead Rhabdovirus (SHRV), the Salmon Alphavirus (SAV) or Nervous Necrosis Virus (NNV). The cell line, however, did not show any increase in cytopathic effect when infected with SHRV or SAV. Similarly, no cytopathic effect was observed in the ifih1-/- cell line when infected with Infectious Pancreatic Necrosis Virus (IPNV), Infectious Haemorrhagic Necrotic Virus (IHNV). These results indicate the redundancy of the antiviral innate defence system in CHSE-derived cells, which helps with circumventing viral evasion strategies.

Pangolin scales as adaptations for innate immunity against pathogens

BackgroundPangolins are the only mammals that have overlapping scales covering most of their bodies, and they play a crucial role in the ecosystem, biological research, and human health and disease. Previous studies indicated pangolin scale might provide an important mechanical defense to themselves. The origin and exact functions of this unique trait remain a mystery. Using a multi-omics analysis approach, we report a novel functional explanation for how mammalian scales can provide host–pathogen defense.ResultsOur data suggest that pangolin scales have a sophisticated structure that could potentially trap pathogens. We identified numerous proteins and metabolites exhibiting antimicrobial activity, which could suggest a role for scales in pathogen defense. Notably, we found evidence suggesting the presence of exosomes derived from diverse cellular origins, including mesenchymal stem cells, immune cells, and keratinocytes. This observation suggests a complex interplay where various cell types may contribute to the release of exosomes and antimicrobial compounds at the interface between scales and viable tissue. These findings indicate that pangolin scales may serve as a multifaceted defense system, potentially contributing to innate immunity. Comparisons with human nail and hair revealed pangolin-specific proteins that were enriched in functions relating to sensing, immune responses, neutrophil degranulation, and stress responses. We demonstrated the antimicrobial activity of key pangolin scale components on pathogenic bacteria by antimicrobial assays.ConclusionsThis study identifies a potential role of pangolin scales and implicates scales, as possible determinants of pathogen defense due to their structure and contents. We indicate for the first time the presence of exosomes in pangolin scales and propose the new functions of scales and their mechanisms. This new mechanism could have implications for multiple fields, including providing interesting new research directions and important insights that can be useful for synthesizing and implementing new biomimetic antimicrobial approaches.

Non-linear programming model proposal for mutual support distance of air defence systems

With the advancements in technology, the deployment of air defence systems required for the defence of a country after procurement is considered as an important problem in terms of defence effectiveness. It is seen that criteria such as coverage, strike effectiveness and logistics network are taken into account while deploying. In addition, principles such as remote countermeasures, defence in depth and all-round defence are also taken into account. In this study, two different deployment models are proposed for point and area air defence. In this model, the optimum deployment distance at which other systems can support each other in addition to a deployed air defence system is determined. In the nonlinear target programming model proposed for point air defence, the number of missiles is considered to be reasonably balanced for perimeter defence, while for area defence, the nonlinear optimization problem is addressed by calculating the equally important coverage and strike effectiveness criteria values. In this study, it is observed that the approach based on mutual support distance has been used for the first time in the defence literature. According to the results obtained, it is observed that this proposed model for determining the mutual support distance solves the deployment problem optimally.

State special transport service in the system of subjects of the Ministry of Defense of Ukraine: directions of influence and the role of public administration for their implementation

It was emphasized that in the conditions of ongoing Russian aggression, the issue of effective and stable functioning of the system of the Ministry of Defense of Ukraine has become important. It is noted that such an intention is possible only thanks to the systematically effective work of all subjects of this system. The exceptional role of the State Special Service of Transport in this aspect is emphasized, given the subject orientation of the latter. We are talking about the transport component, which is one of the basic prerequisites for the successful implementation of the lion’s share of measures by subjects not only of the ministry system, but also of the entire security and defense sector. The position of the State Special Service of Transport as a subject of public-legal relations at the current stage of law-making is highlighted in general outlines. It was found that it is appropriate to talk about an institution endowed with the status of a specialized military formation, which carries out a number of defense measures peculiar only to it. Despite its regulatory specifics, it is advisable to talk about a number of similar parameters, compared to the rest of the institutions. The essence of the directions of the analyzed body’s work, including under the current situation, is outlined and disclosed. Arguably, it is emphasized that such directions are derived from the functions of the institution, which the latter’s officials implement in practice. The legislator’s position on their gradation into two fundamental groups was supported and developed: 1) peacetime; 2) a special period. Based on this, the author’s vision of the quantitative and specific composition of the areas of work of the State Special Service of Transport is proposed, followed by their general characteristics. The problems of the importance of public administration tools in the framework of the implementation of management functions performed by this specialized military formation have been studied. It is emphasized that the presence of these tools is a prerequisite for the implementation of management steps. The above constitutes a critical and unalternative position from the point of view of the application of appropriate measures within the limits of one or another outlined direction. Based on the preliminary results, an attempt was made to determine the place of the State Special Transport Service in the structure of the Ministry of Defense system. Based on the competence of the institution, directions of influence and awareness of the role of the stability of the transport component, a well-argued assumption is made about the uniquely important role of this institution.

Effect of a Commercial Polyphenol Compound on the Performance and Antioxidant Status of Penaeus vannamei

The study evaluated the effect of a commercial polyphenol (ELIFE®) on the growth performance and antioxidant defense system of Penaeus vannamei juveniles. The study was completely randomized with three experimental groups and eight repetitions, divided into two 28-day phases. The experimental groups consisted of different dietary inclusion levels of ELIFE® (0.0, 0.5, and 1.0 g kg−1). Five shrimps were stocked in each experimental unit. Growth performance, oxidative stress, and enzymatic activity in shrimp hepatopancreas were assessed. In Phase 1, shrimp fed ELIFE®, regardless of inclusion level, displayed higher specific growth rate, final weight, and final length than the control group. In Phase 2, shrimp fed 1.0 g kg−1 ELIFE® showed higher final biomass and SGR than all other experimental groups; they also displayed increased reduced glutathione and glutathione-S-transferase activities. In both test phases, shrimp fed 1.0 g kg−1 ELIFE® presented increased glutathione reductase activity compared to all other experimental groups. In both test phases, shrimp fed ELIFE®, regardless of inclusion level, exhibited increased glutathione peroxidase activity compared to control groups. Thus, ELIFE® enhanced the antioxidant defense system of P. vannamei and led to better shrimp performance and survival. This study recommends dietary supplementation with 1.0 g kg−1 ELIFE® for P. vannamei juveniles.

Unmanned surface vehicles for naval warfare and maritime security

There is a growing need to implement maritime defensive systems, covering both medium-range and close-in defenses. This is in response to the escalating threat posed by unmanned surface vehicles (USVs) in a rapidly changing environment. As unmanned technologies become more widespread and advanced, the proactive deployment of these defensive measures is becoming imperative. This strategic approach aims to reduce risks, protect vital assets, and bolster the Navy’s flexibility in adapting to the evolving dynamics of contemporary naval warfare. This initiative aligns with broader goals of upholding maritime security and contributing to regional stability amid rapidly shifting conditions in warfare. This perspective covers the relevant aspects of USV development, and the countermeasures being considered.

Tandem mobilization of anti-phage defenses alongside SCCmec elements in staphylococci

Recent research has identified multiple immune systems that bacteria use to protect themselves from viral infections. However, little is known about the mechanisms by which these systems horizontally spread, especially among bacterial pathogens. Here, we investigate antiviral defenses in staphylococci, opportunistic pathogens that constitute leading causes of antibiotic-resistant infections. We show that these organisms harbor a variety of anti-phage defenses encoded within or near SCC (staphylococcal cassette chromosome) mec cassettes, mobile genomic islands that confer methicillin resistance. Importantly, we demonstrate that SCCmec-encoded recombinases mobilize not only SCCmec, but also tandem SCC-like cassettes enriched in genes coding for diverse defense systems. Further, we show that phage infection stimulates cassette mobilization (i.e. excision and circularization). Thus, our findings indicate that SCC/SCCmec cassettes not only spread antibiotic resistance but can also play a role in mobilizing anti-phage defenses.

Level of prooxidant-antioxidant status in highly productive cows with comorbid obstetric, gynecological and orthopedic pathology

The lipid peroxidation and antioxidant defense system is a balanced system responsible for the processing and utilization of lipids in the body’s cells. It plays an important role in lipid metabolism, cell protection and overall health of the body. Its proper functioning is necessary to ensure optimal functioning of cells and organs throughout the body. The article clinically and experimentally substantiates the pathogenetic role of lipid peroxidation products and the level of antioxidant protection in cows with endometritis and purulent-necrotic processes in the finger area, as well as with the comorbid course of endometritis and orthopedic pathology. It has been shown that multimorbid manifestation is accompanied by a more severe course than individual diseases. It has been established that the development of postpartum endometritis and purulent-necrotic lesions of the limbs in cows is accompanied by a highly significant increase in lipid peroxidation products in the blood serum against the background of a decrease in the amount of antioxidant enzymes, with the exception of ceruloplasmin. Moreover, these changes are accompanied by a sharp jump in the comorbid course of endometritis and orthopedic pathology in highly productive animals.

Protective effect of reduced glutathione on acute kidney injury in lung cancer patients treated with cisplatin: a retrospective cohort study

Background Cisplatin is a common cause of acute kidney injury (AKI) during chemotherapy for lung cancer, and the nephrotoxicity limits its clinical use. Reduced glutathione (GSH) is a major component of the cellular antioxidant defense system and performs important physiological functions. The aim of this study was to analyze the protective effect of GSH on AKI in lung cancer patients treated with cisplatin. Methods The clinical data were retrospectively collected from lung cancer patients treated with cisplatin at our hospital between 1 January and 31 December 2019. The patients were divided into AKI group and non-AKI group based on whether AKI occurred, and into GSH group and non-GSH group based on whether GSH was used. Univariate and multivariate logistic regressions were used to analyze the risk factors for AKI. Results A total of 1372 lung cancer patients treated with cisplatin were enrolled. Of these patients, 231 patients (16.8%) developed AKI. The incidence of AKI was lower in the GSH group compared with the non-GSH group (10.6% vs. 18%, p = 0.009). Multivariate logistic regression analysis indicated that older age (OR = 1.045, 95% CI 1.025–1.065, p < 0.001), anemia (OR = 2.436, 95% CI 1.800–3.298, p < 0.001), higher SUA levels (OR = 1.002, 95% CI 1.000–1.004, p = 0.012), higher total amount of cisplatin per cycle (OR = 1.015, 95% CI 1.004–1.025, p = 0.005), and combination with paclitaxel (OR = 2.099, 95% CI 1.435–3.070, p < 0.001) were independent risk factors for AKI in lung cancer patients treated with cisplatin, whereas GSH (OR = 0.573, 95% CI 0.353–0.931, p = 0.025) and mannitol (OR = 0.229, 95% CI 0.055–0.963, p = 0.044) reduced the risk of AKI. Conclusion GSH was an independent protective factor against AKI in lung cancer patients treated with cisplatin and could be considered for clinical use in these patients to better protect renal function.

Systematic, high-throughput characterization of bacteriophage gene essentiality on diverse hosts.

Understanding core and conditional gene essentiality is crucial for decoding genotype-phenotype relationships in organisms. We present PhageMaP, a high-throughput method to create genome-scale phage knockout libraries for systematically assessing gene essentiality in bacteriophages. Using PhageMaP, we generate gene essentiality maps across hundreds of genes in the model phage T7 and the non-model phage Bas63, on diverse hosts. These maps provide fundamental insights into genome organization, gene function, and host-specific conditional essentiality. By applying PhageMaP to a collection of anti-phage defense systems, we uncover phage genes that either inhibit or activate eight defenses and offer novel mechanistic hypotheses. Furthermore, we engineer synthetic phages with enhanced infectivity by modular transfer of a PhageMaP-discovered defense inhibitor from Bas63 to T7. PhageMaP is generalizable, as it leverages homologous recombination, a universal cellular process, for locus-specific barcoding. This versatile tool advances bacteriophage functional genomics and accelerates rational phage design for therapy.