Pathogen Inactivation

BACKGROUND: Carbapenem-resistant P. aeruginosa (CRPA) is a common hospital-acquired bacterium. It exhibits high resistance to many antibiotics, including ceftazidime/avibactam and cefteolozane/tazobactam . The presence of carbapenem-resistant genes and co-existence Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBLs) further inactivated all β-lactams. Understanding the resistance genes of CRPA can help in uncovering the resistance mechanism and guiding anti-infective treatment...

The global spread of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b virus since 2021 necessitates a re-evaluation of the role of vaccination in controlling HPAI outbreaks among poultry, which has been controversial because of the concern of silent spread with viral mutation and spillover to human. We systematically reviewed and meta-analyzed all existing data from experimental challenge trials to assess the efficacy of HPAI vaccines against mortality in specific pathogen free (SPF) chickens, with evaluation of the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach...

Antimicrobial photoinactivation (API) has shown some promise in potentially treating different nosocomial bacterial infections, however, its application on staphylococci, especially other than Staphylococcus aureus or methicillin-resistant S. aureus (MRSA) species is still limited. Although S. aureus is a well-known and important nosocomial pathogen, several other species of the genus, particularly coagulase-negative Staphylococcus (CNS) species such as Staphylococcus epidermidis and Staphylococcus saprophyticus , can also cause healthcare-associated infections and foodborne intoxications...

Enterotoxigenic Escherichia coli (ETEC) is an important type of pathogenic bacteria that causes diarrhea in pigs. The objective of this study was to prepare a novel tetravalent vaccine to effectively prevent piglet diarrhea caused by E. coli. In order to realize the production of K88ac-K99-ST 1 -LT B tetravalent inactivated vaccine, the biological characteristics, stability, preservation conditions, and safety of the recombinant strain BL21(DE3) (pXKKSL4) were studied, and the vaccine efficacy and minimum immune dose were measured...

Pseudomonas syringae is a gram-negative plant pathogen that infects plants such as tomato and poses a threat to global crop production. In this study, a novel lytic phage infecting P. syringae pv. tomato DC3000, named phage D6, was isolated and characterized from sediments in a karst cave. The latent period of phage D6 was found to be 60 min, with a burst size of 16 plaque-forming units per cell. Phage D6 was stable at temperatures between 4 and 40 °C but lost infectivity when heated to 70 °C...

BACKGROUND: Goat milk is considered a nutritionally superior resource, owing to its advantageous nutritional attributes. Nevertheless, it is susceptible to spoilage and the persistence of pathogens. Electron beam irradiation stands as a promising non-thermal processing technique capable of prolonging shelf life with minimal residue and a high degree of automation. RESULTS: The effects of electron beam irradiation (2, 3, 5, and 7 kGy) on microorganisms, physicochemical properties, and protein structure and compared with conventional pasteurized goat milk (PGM)...

BACKGROUND: Pathogen inactivation treatment (PIT) has been shown to alter platelet function, phenotype, morphology and to induce a faster aging of platelet concentrates (PCs). Key pieces of information are still missing to understand the impacts of PITs at the cellular level. OBJECTIVES: This study investigated the impact of amotosalen/UVA on PCs, from a post-translational modifications (PTM) point of view. Phosphoproteomic analyses were conducted on resting platelets, right after the amotosalen/UVA treatment and compared with untreated PCs...

Penicillin-binding protein 2 (PBP2) plays a key role in the formation of peptidoglycans in bacterial cell walls by crosslinking glycan chains through transpeptidase activity. PBP2 is also found in Campylobacter jejuni, a pathogenic bacterium that causes food-borne enteritis in humans. To elucidate the essential structural features of C. jejuni PBP2 (cjPBP2) that mediate its biological function, we determined the crystal structure of cjPBP2 and assessed its protein stability under various conditions. cjPBP2 adopts an elongated two-domain structure, consisting of a transpeptidase domain and a pedestal domain, and contains typical active site residues necessary for transpeptidase activity, as observed in other PBP2 proteins...

The complement cascade comprises a variety of soluble and cell surface proteins and is an important component of the innate immune system. When the cascade is triggered by any of the three activation pathways, the complement system rapidly produces large amounts of protein fragments that are potent mediators of inflammatory, vasoactive, and metabolic responses. All activation pathways lead to the terminal complement cascade with the formation of the membrane attack complex, which lyses cells by forming membrane pores...

UNLABELLED: Salmonella enterica serovar Typhi and Paratyphi A are the cause of typhoid and paratyphoid fever in humans, which are systemic life-threatening illnesses. Both serovars are exclusively adapted to the human host, where they can cause life-long persistent infection. A distinct feature of these serovars is the presence of a relatively high number of degraded coding sequences coding for metabolic pathways, most likely a consequence of their adaptation to a single host. As a result of convergent evolution, these serovars shared many of the degraded coding sequences although often affecting different genes in the same metabolic pathway...

BACKGROUND: The fight against COVID-19 requires mass vaccination strategies, and vaccines inducing durable cross-protective responses are still needed. Inactivated vaccines have proven lasting efficacy against many pathogens and good safety records. They contain multiple protein antigens that may improve response breadth and can be easily adapted every year to maintain preparedness for future seasonally emerging variants. METHODS: The vaccine dose was determined using ELISA and pseudoviral particle-based neutralization assay in the mice...

Aspartate kinase (AK), an enzyme from the Wolbachia endosymbiont of Brugia malayi (WBm), plays a pivotal role in the bacterial cell wall and amino acid biosynthesis, rendering it an attractive candidate for therapeutic intervention. Allosteric inhibition of aspartate kinase is a prevalent mode of regulation across microorganisms and plants, often modulated by end products such as lysine, threonine, methionine, or meso-diaminopimelate. The intricate and diverse nature of microbial allosteric regulation underscores the need for rigorous investigation...

Inflammasomes are complex platforms for the cleavage and release of inactivated IL-1β and IL-18 cytokines that trigger inflammatory responses against damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs). Gut microbiota plays a pivotal role in maintaining gut homeostasis. Inflammasome activation needs to be tightly regulated to limit aberrant activation and bystander damage to the host cells. Several types of inflammasomes, including Node-like receptor protein family (e...

UNLABELLED: Spores of Bacillus subtilis germinate in response to specific germinant molecules that are recognized by receptors in the spore envelope. Germinants signal to the dormant spore that the environment can support vegetative growth, so many germinants, such as alanine and valine, are also essential metabolites. As such, they are also required to build the spore. Here we show that these germinants cause premature germination if they are still present at the latter stages of spore formation and beyond, but that B...

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social and communication deficits and repetitive behaviors. The genetic heterogeneity of ASD presents a challenge to the development of an effective treatment targeting the underlying molecular defects. ASD gating charge mutations in the KCNQ /KV 7 potassium channel cause gating pore currents (Igp ) and impair action potential (AP) firing of dopaminergic neurons in brain slices. Here, we investigated ASD gating charge mutations of the voltage-gated SCN2A /NaV 1...

In the early COVID-19 pandemic with urgent need for countermeasures, we aimed at developing a replicating viral vaccine using the highly efficacious measles vaccine as vector, a promising technology with prior clinical proof of concept. Building on our successful pre-clinical development of a measles virus (MV)-based vaccine candidate against the related SARS-CoV, we evaluated several recombinant MV expressing codon-optimized SARS-CoV-2 spike glycoprotein. Candidate V591 expressing a prefusion-stabilized spike through introduction of two proline residues in HR1 hinge loop, together with deleted S1/S2 furin cleavage site and additional inactivation of the endoplasmic reticulum retrieval signal, was the most potent in eliciting neutralizing antibodies in mice...

Tumor necrosis factor receptor-associated factor family member-associated NF-κB activator-binding kinase 1 (TBK1) plays a key role in the induction of the type 1 interferon (IFN-I) response, which is an important component of innate antiviral defense. Viruses target calcium (Ca2+ ) signaling networks, which participate in the regulation of the viral life cycle, as well as mediate the host antiviral response. Although many studies have focused on the role of Ca2+ signaling in the regulation of IFN-I, the relationship between Ca2+ and TBK1 in different infection models requires further elucidation...

The healthcare-associated infections (HAIs) and pandemics caused by multidrug-resistant (MDR) and new-generation pathogens threaten the whole world community. Cu and its alloys have been attracting widespread interest as anti-contamination materials due to the rapid inactivation of MDR-superbugs and viruses. Applying thin Cu-based foils on pre-existing surfaces in hygiene-sensitive areas represents a quick, simple, cost-effective self-sanitising practice. However, the influence of chemical composition and microstructure should be deeply investigated when evaluating the antimicrobial capability and durability of Cu-based materials...

BACKGROUND: Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch-like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS-associated tumors. Moreover, translating tumor testing results into patient management remains controversial. Our aim is to assess the challenges associated with the implementation of tumoral MMR gene testing in routine workflows...

Herein, ultraviolet B (UVB) persistent luminescence phosphors containing SrAl12 O19 : Ce3+ , Sc3+ nanoparticles were reported. Thermoluminescence (TL) spectrum analysis reveals that the shallow trap induced by Sc3+ co-doping plays an important role in photoluminescence persistent luminescence (PersL) development, while the deep trap dominates the generation of optical stimulated luminescence (OSL). Owing the appearance of deep trap, the OSL is observed under light (700 nm - 900 nm) excitation. UVB luminescence exerts good bactericidal effects on pathogenic bacteria involved in the process of food spoilage...