Search Results (35)

The description of the organization of microorganisms in terms of emergent “social” interactions has long been a fascinating and challenging subject, in both biology and sociology. In these organisms, the role of the individual is far less dominant than that of the community, which operates as a sort of superorganism. The coordination is achieved through a communication mechanism known as quorum sensing. Quorum sensing coordinates and regulates various biological aspects of a microbial community, such as the expression of pathogenicity factors, biofilm formation, and the production of secondary metabolites, among others. These processes rely on the coordinated behavior of the entire bacterial population, enabling them to adapt and thrive withing a specific ecological niche under its unique biological, physical and chemical conditions. Finally, quorum sensing also allows the community to control the development of potentially harmful individuals, thus preserving the cooperativeness of the community. This study uses an agent-based quorum sensing model to explore the relationship between metabolic functions and social behavior in bacteria. In particular, we identify two metabolic parameters whose variations provide a broad panorama of possible social characteristics. Furthermore, the proposed QS model allows us to reproduce, at least qualitatively, some experimental results regarding the competition between some strains with different social characteristics. Finally, we examine how an ideal polyculture responds to variations in the metabolic characteristics of its components. Specifically, we identify a particularly stable condition in which the components cooperate to maximize the overall health of the colony. We refer to this state as resonance for life. Full article

Nowadays, Internet of Things (IoT) is one of the most dynamically evolving services in the 5G ecosystem. In industrial IoT (IIoT), this service can be utilized to deliver state updates of various equipment to the remote control center for further coordination and maintenance. As a result, one of the critical metrics of interest for such a service is the Age of Information (AoI) and its upper bound—peak AoI (AoI)—characterizing the freshness of information about the state of the systems. In spite of significant attention, these metrics received over the last decade, only little is known regarding the PAoI performance of a single source (e.g., sensor) in the presence of competing traffic from other sources in queuing systems. On top of this, models with batch arrivals and batch services that can be effectively used to represent service performance in modern cellular systems such as 5G New Radio are lacking. In our study, we consider a cellular air interface representing it as a queuing system (QS) in discrete-time with batch arrivals and service and investigate performance of a single (tagged) source in presence of competing traffic from other sources having the same priority, where all the sources are modeled using the switched Poisson process (SPP) characterized by sophisticated correlational properties. We also investigated the impact of several service disciplines on the performance of the tagged source including first-come–first-served (FCFS), last-come–first-served (LCFS), random, and priority-based service. Our results illustrate that, although the qualitative behavior of the mean PAoI is different for different service disciplines, the optimal value of PAoI is insensitive to the choice of the service order. On top of this, we observed that introducing a priority in service to one of the flows may drastically affect the performance of other flows even when the overall load contribution of a single flow is rather limited. Our observations can be utilized to design packet scheduling strategies for 4G/5G cellular systems carrying traffic of state update applications. Full article

Quorum sensing (QS) is a molecular communication mechanism among bacterial cells. It is critical in regulating virulence factors, motility, antibiotic resistance, and biofilm formation. Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen linked to healthcare-associated infections, food poisoning, and biofilm formation. Treating infections caused by pathogenic bacteria has become a challenge due to the development of multi-antibiotic resistance upon continuous exposure of bacteria to antibiotics. An alternative strategy to conventional antimicrobials to decrease the bacterial pathogenicity is QS inhibition, also known as quorum quenching. Using plant-derived compounds is an environmentally friendly strategy to block the bacterial QS and inhibit bacterial growth. Portulaca oleracea is a popular plant in different countries and is also used in traditional medicine. It is widely consumed raw in salads and as garnishes, though it can be cooked as a vegetarian dish. This study evaluates the antimicrobial activity of the methanolic extract of P. oleracea and its effectiveness in blocking or attenuating the QS of P. aeruginosa. The agar well diffusion method used for screening the antibacterial activity showed a significant growth inhibition of P. aeruginosa by the extract at 500 mg/mL with a minimum inhibitory concentration of 31.25 mg/mL. A bioindicator bacterium, Chromobacterium violaceum CV026, was used to determine the effect of the methanolic extract on the QS of P. aeruginosa. The results indicated a significant reduction in biofilm formation, pyocyanin production, and LasA staphylolytic activity. The phytochemical analysis by Gas Chromatography–Mass Spectrometry showed that the methanolic extract contained several phenols, alkaloids, esters, and other compounds previously reported to have antibacterial and antioxidant effects. These findings highlight the effectiveness of P. oleracea methanolic extract in attenuating the QS and virulence factors of P. aeruginosa. This study suggests that P. oleracea is an important source of natural antimicrobials and its use would be beneficial in food and pharmaceutical applications. Full article

Antibiotic resistance is a major problem and a major global health concern. In total, there are 16 million deaths yearly from infectious diseases, and at least 65% of infectious diseases are caused by microbial communities that proliferate through the formation of biofilms. Antibiotic overuse has resulted in the evolution of multidrug-resistant (MDR) microbial strains. As a result, there is now much more interest in non-antibiotic therapies for bacterial infections. Among these revolutionary, non-traditional medications is quorum sensing inhibitors (QSIs). Bacterial cell-to-cell communication is known as quorum sensing (QS), and it is mediated by tiny diffusible signaling molecules known as autoinducers (AIs). QS is dependent on the density of the bacterial population. QS is used by Gram-negative and Gram-positive bacteria to control a wide range of processes; in both scenarios, QS entails the synthesis, identification, and reaction to signaling chemicals, also known as auto-inducers. Since the usual processes regulated by QS are the expression of virulence factors and the creation of biofilms, QS is being investigated as an alternative solution to antibiotic resistance. Consequently, the use of QS-inhibiting agents, such as QSIs and quorum quenching (QQ) enzymes, to interfere with QS seems like a good strategy to prevent bacterial infections. This review sheds light on QS inhibition strategy and mechanisms and discusses how using this approach can aid in winning the battle against resistant bacteria. Full article

The Investigator ESSplex SE QS Kit (Qiagen) is a next-generation polymerase chain reaction (PCR) kit that, in 60 min, amplifies 17 Short Tandem Repeat (STR) markers, including the five European Standard Set (ESS) loci (D10S1248, D12S391, D1S1656, D22S1045, D2S441), the SE33 marker, and the locus Amelogenin for sex determination. Two quality sensors (QS1 and QS2) are also co-amplified to check PCR performance. Since forensic laboratories carry out hundreds of DNA typings annually, we verified the kit’s performance using half reaction volumes with the aim of improving the number of samples that may be amplified with a single kit and consequently reducing laboratory costs. In the present study, intended as a technical note rather than internal validation, some control samples (oral swabs) with known DNA profiles and 40 real casework samples were analyzed. We observed that reducing the total reaction volume, while keeping all component ratios unaltered, yields DNA profiles comparable to those obtained using standard reaction volumes and with allele peaks higher than those with regular volumes. Using half volumes for PCR amplification enables the analysis of a larger number of samples compared to the standard protocol, thereby reducing laboratory costs without compromising the quality of the analysis. Full article

In the present study, norlobaridone (NBD) was isolated from Parmotrema and then evaluated as a new potent quorum sensing (QS) inhibitor against Pseudomonas aeruginosa biofilm development. This phenolic natural product was found to reduce P. aeruginosa biofilm formation (64.6% inhibition) and its related virulence factors, such as pyocyanin and rhamnolipids (% inhibition = 61.1% and 55%, respectively). In vitro assays inhibitory effects against a number of known LuxR-type receptors revealed that NBD was able to specifically block P. aeruginosa’s LasR in a dose-dependent manner. Further molecular studies (e.g., sedimentation velocity and thermal shift assays) demonstrated that NBD destabilized LasR upon binding and damaged its functional quaternary structure (i.e., the functional dimeric form). The use of modelling and molecular dynamics (MD) simulations also allowed us to further understand its interaction with LasR, and how this can disrupt its dimeric form. Finally, our findings show that NBD is a powerful and specific LasR antagonist that should be widely employed as a chemical probe in QS of P. aeruginosa, providing new insights into LasR antagonism processes. The new discoveries shed light on the mysterious world of LuxR-type QS in this key opportunistic pathogen. Full article

Improving the availability of new sources of probiotics is essential to continue implementing alternative solutions to improve coral health; one such source is urban corals. However, little is known about urban coral’s health status and whether they can harbor bacteria exhibiting probiotic traits. Here, we explored the status of the urban coral Madracis auretenra and the presence of probiotic traits in its associated culturable bacteria. After assessing ecological attributes, we observed a similar abundance (cover %) when comparing patches of M. auretenra occurring in both an urban site and a marine protected area. The urban patch also exhibited a high abundance of vibrios in coral tissues and signs of ecosystem deterioration. However, this patch showed a “good” health index condition; so, we hypothesized the presence of beneficial bacteria. We isolated 132 bacterial strains from this healthy urban M. auretenra. These bacteria were affiliated with 11 genera, including Vibrio, Shewanella, Bacillus, Exiguobacterium, Priestia, and Niallia, among others. Screenings revealed the predominant presence of potential probiotic traits such as catalase, antiQS, and the production of siderophores activities among the bacterial isolates. We proposed a list of 24 bacterial isolates as probiotic precandidates that jointly exhibited three or more of these traits, among which the Vibrio and Bacilli strains stand out. We provide insights into the health status of this urban coral and its potential as a source of bacteria exhibiting potential probiotic traits. Full article

An unconjugated composite peptide vaccine targeting multiple conserved influenza epitopes from hemagglutinin, neuraminidase, and matrix protein and formulated with a safe and highly potent adjuvant, Army Liposome formulation (ALFQ), generated broad and durable immune responses in outbred mice. The antibodies recognized specific epitopes in influenza peptides and several human, avian, and swine influenza viruses. Comparable antibody responses to influenza viruses were observed with intramuscular and intradermal routes of vaccine administration. The peptide vaccine induced cross-reactive antibodies that recognized influenza virus subtypes A/H1N1, A/H3N2, A/H5N1, B/Victoria, and B/Yamagata. In addition, immune sera neutralized seasonal and pandemic influenza strains (Group 1 and Group 2). This composite multi-epitope peptide vaccine, formulated with ALFQ and administered via intramuscular and intradermal routes, provides a high-performance supra-seasonal vaccine that would be cost-effective and easily scalable, thus moving us closer to a viable strategy for a universal influenza vaccine and pandemic preparedness. Full article

Quorum sensing (QS) in Pseudomonas aeruginosa plays an essential role in virulence factors, biofilm formation as well as antibiotic resistance. Approaches that target virulence factors are known to be more sustainable than antibiotics in weakening the infectivity of bacteria. Although honey has been shown to exert antipseudomonal activities, the enhancement of such activity in ginger-enriched honey is still unknown. The main objective of this study was to determine the impacts of honey and ginger-enriched honey on the QS virulence factors and biofilm formation of antibiotic resistant P. aeruginosa clinical isolates. Outcomes showed honey and/or ginger-enriched honey significantly reduced the protease activity, pyocyanin production and exotoxin A concentration of the isolates. The swarming and swimming motility together with biofilm formation in all clinical isolates were also significantly inhibited by both honey samples. Notable morphological alteration of bacterial cells was also observed using scanning electron microscopy. A principal component analysis (PCA) managed to distinguish the untreated group and treatment groups into two distinct clusters, although honey and ginger-enriched honey groups were not well differentiated. This study revealed the effectiveness of honey including ginger-enriched honey to attenuate QS virulence factors and biofilm formation of P. aeruginosa. Full article

Length polymorphisms of polyglutamine (polyQs) in triplet-repeat-disease-causing genes have diversified during primate evolution despite them conferring a risk of human-specific diseases. To explain the evolutionary process of this diversification, there is a need to focus on mechanisms by which rapid evolutionary changes can occur, such as alternative splicing. Proteins that can bind polyQs are known to act as splicing factors and may provide clues about the rapid evolutionary process. PolyQs are also characterized by the formation of intrinsically disordered (ID) regions, so I hypothesized that polyQs are involved in the transportation of various molecules between the nucleus and cytoplasm to regulate mechanisms characteristic of humans such as neural development. To determine target molecules for empirical research to understand the evolutionary change, I explored protein–protein interactions (PPIs) involving the relevant proteins. This study identified pathways related to polyQ binding as hub proteins scattered across various regulatory systems, including regulation via PQBP1, VCP, or CREBBP. Nine ID hub proteins with both nuclear and cytoplasmic localization were found. Functional annotations suggested that ID proteins containing polyQs are involved in regulating transcription and ubiquitination by flexibly changing PPI formation. These findings explain the relationships among splicing complex, polyQ length variations, and modifications in neural development. Full article

Pseudomonas aeruginosa, a life-threatening bacteria listed as a priority pathogen by World Health Organization WHO, is known to cause severe nosocomial infections and fatality in immunocompromised individuals through its quorum sensing (QS) mediated biofilm formation. P. aeruginosa’s antibiotic-resistant biofilms are highly challenging to the existing antibiotic treatment options. There is an urgent clinical need to develop novel alternative therapeutic molecules such as antibiofilm and antiquorum sensing agents to counter the emergence of an unprecedented pace of antibiotic resistance of pathogens. In this context, a library of seventy 3-amidocoumarin derivatives was designed, and docking studies were performed against the P. aeruginosa LasR receptor using AutoDock 4.0. Based on docking results, a final series of sixteen 3-amidocoumarin derivatives (4a–p) were synthesized and evaluated for antibiofilm activity in vitro. Eight compounds significantly inhibited the formation of P. aeruginosa PAO1 biofilm. Compounds 4f, 4l and 4o showed maximum % inhibition in antibiotic-resistant P. aeruginosa PAO1 biofilm formation in the range of 80% to 86%. Further, the structure–activity relationship (SAR) studies revealed that the presence of electron-donating and bromo substituents at benzamido and coumarin moieties, respectively, effectively enhances the antibiofilm activity. In addition, the binding interactions between the synthesized compounds and active sites of the LasR QS receptor (Protein Data Bank Code: 2uv0) in P. aeruginosa were also investigated by molecular docking. The high binding affinities indicate that these compounds might be suitable for development into potent inhibitors of QS and biofilm disruptors. Full article

The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more transmissible, with a reduced sensitivity to vaccines targeting the original virus strain. Therefore, developing an effective vaccine against both the original SARS-CoV-2 strain and its variants is an urgent need. It is known that the receptor-binding domain (RBD) in the S protein of SARS-CoV-2 is an important vaccine target, but subunit vaccines usually have lower immunogenicity and efficacy. Thus, selecting appropriate adjuvants to enhance the immunogenicity of protein-based subunit vaccine antigens is necessary. Here, an RBD-Fc subunit vaccine of SARS-CoV-2 has been generated, followed by vaccination in B6 mice, and four adjuvant regimens were investigated, including aluminum salts (Alum) + 3-O-desacyl-4′-monophosphoryl lipid A (MPL), AddaVax, QS21 + MPL, and Imiquimod. The adjuvant potency was evaluated by comparing the elicited polyclonal antibodies titers with measuring binding to RBD and S protein in ELISA and Western blot analysis, and also the cross-neutralizing antibodies titers using a pseudovirus infection assay of hACE2-expressing 293T cells, with pseudoviruses expressing the S protein of the SARS-CoV-2 original strain and Delta strain. The presence of QS21 + MPL adjuvant induced stronger polyclonal antibody response and neutralization potency blocking the original strain and Delta strain, as compared with the non-adjuvant RBD-Fc group and other adjuvant groups. Meanwhile, Imiquimod even had a negative effect in inducing specific antibodies and cross-neutralizing antibody production as an adjuvant. Full article

An imbalance in gut microbiota, termed dysbiosis, has been shown to affect host health. Several factors, including dietary changes, have been reported to cause dysbiosis with its associated pathologies that include inflammatory bowel disease, cancer, obesity, depression, and autism. We recently demonstrated the inhibitory effects of artificial sweeteners on bacterial quorum sensing (QS) and proposed that QS inhibition may be one mechanism behind such dysbiosis. QS is a complex network of cell–cell communication that is mediated by small diffusible molecules known as autoinducers (AIs). Using AIs, bacteria interact with one another and coordinate their gene expression based on their population density for the benefit of the whole community or one group over another. Bacteria that cannot synthesize their own AIs secretly “listen” to the signals produced by other bacteria, a phenomenon known as “eavesdropping”. AIs impact gut microbiota equilibrium by mediating intra- and interspecies interactions as well as interkingdom communication. In this review, we discuss the role of QS in normobiosis (the normal balance of bacteria in the gut) and how interference in QS causes gut microbial imbalance. First, we present a review of QS discovery and then highlight the various QS signaling molecules used by bacteria in the gut. We also explore strategies that promote gut bacterial activity via QS activation and provide prospects for the future. Full article

In addition to volatile compounds, metabolites also have a great effect on the flavour of food. Fresh finger citron cannot be eaten directly because of its spicy and bitter taste, so it is made into a preserved fruit product known as Laoxianghuang (LXH). To investigate the metabolites that have an effect on the flavour of LXH, untargeted metabolomics was performed using an ultrahigh-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS), and the metabolites of the Laoxianghuang samples from different locations in the Chaoshan area were compared and analysed. A total of 756 metabolites were identified and distinct differences were revealed among the different Laoxianghuang samples. A total of 33 differential metabolites with the most significant changes were screened through further multivariate analytical steps, and each group of samples had unique metabolites. For instance, pomolic acid had the highest content in the JG sample, while L-glycyl-L-isoleucine was rich in the QS sample. Moreover, flavonoid metabolites made the greatest contribution to the unique flavour of Laoxianghuang. The metabolic pathways involved are the biosynthetic pathways of flavonoids, isoflavonoids, flavones, and flavonols. This study can provide some creative information for distinguishing the quality differences of Laoxianghuang from the perspective of metabolites and offer preliminary theoretical support to characterise the formation of flavour substances in Laoxianghuang. Full article

The gut microbiome can produce metabolic products that exert diverse activities, including effects on the host. Short chain fatty acids and amino acid derivatives have been the focus of many studies, but given the high microbial density in the gastrointestinal tract, other bacterial products such as those released as part of quorum sensing are likely to play an important role for health and disease. In this review, we provide of an overview on quorum sensing (QS) in the gastrointestinal tract and summarise what is known regarding the role of QS molecules such as auto-inducing peptides (AIP) and acyl-homoserine lactones (AHL) from commensal, probiotic, and pathogenic bacteria in intestinal health and disease. QS regulates the expression of numerous genes including biofilm formation, bacteriocin and toxin secretion, and metabolism. QS has also been shown to play an important role in the bacteria–host interaction. We conclude that the mechanisms of action of QS at the intestinal neuro–immune interface need to be further investigated. Full article