Nucleos(t)ide analogs constitute a diverse group of compounds derived from nucleosides and nucleotides, playing a crucial role in various biological processes. These analogs exhibit a wide range of applications, including their use as additives, antiviral, and anticancer agents, which makes them valuable in food and medical research. In this review, we will explore the applications of nucleos(t)ide analogs across different fields and discuss the latest advances in engineering and optimization strategies aimed at improving their production efficiency and tailoring their properties for specific purposes. The article focuses on the design of microbial cell factories and their critical role in the production of nucleos(t)ide analogs. By leveraging microbial biosynthesis pathways and employing strategies such as metabolic engineering, researchers are optimizing the synthesis pathways of nucleos(t)ide analogs. This optimization enhances both the yield and diversity of nucleos(t)ide analogs, leading to the creation of novel compounds with enhanced bioactivity and therapeutic potential. Consequently, these efforts are driving significant advancements in drug discovery and biotechnology.

Extracellular vesicles (EVs) are cell membrane-derived structures between 20-400 nm in size. In bacteria, EVs play a crucial role in molecule secretion, cell wall biogenesis, cell-cell communication, biofilm development, and host-pathogen interactions. Despite these increasing reports of bacterial-derived vesicles, there remains a limited number of studies that summarize oral bacterial EVs, their cargo, and their main biological functions. Therefore, the aim of this review is to present the latest research on oral bacteria-derived EVs and how they can modulate various physiological and pathological processes in the oral cavity, including the pathogenesis of highly relevant diseases such as dental caries and periodontitis and their systemic complications. Overall, caries-associated bacteria (such as ) as well as periodontal pathogens (including the red complex pathogens , , and ) have all been shown to produce EVs that carry an array of virulent factors and molecules involved in biofilm and immune modulation, bacterial adhesion, and extracellular matrix degradation. As bacterial EV production is strongly impacted by genotypic and environmental variations, the inhibition of EV genesis and secretion remains a key potential future approach against oral diseases.

The burgeoning proliferation of infections attributed to multidrug-resistant (MDR) bacterial pathogens is profoundly undermining conventional chemotherapeutic modalities, portending a grave menace to global public health. The propagation of drug resistance among bacteria is fundamentally facilitated by bacterial interactions, with extracellular vesicles (EVs) assuming a critical role in interbacterial communication. Here, we briefly delineate the methodologies for isolation, extraction, and characterization of EVs from both Gram-negative and Gram-positive bacterial origins. We further investigate assorted methodologies to augment EV production, embracing physical stimulation, chemical elicitation, and genetic engineering. Moreover, we expound on the pivotal involvement of EVs in the facilitation of bacterial drug resistance proliferation and anticipate future trajectories of research and application potential. This overview of EV-mediated novel mechanisms of horizontal gene transfer implicated in antibiotic resistance among bacteria aims to obstruct the transmission conduits of bacterial drug resistance and thus fortify public health integrity.

Antibiotic resistance has expanded as a result of the careless use of antibiotics in the medical field, the food industry, agriculture, and other industries. By means of genetic recombination between commensal and pathogenic bacteria, the microbes obtain antibiotic resistance genes (ARGs). In bacteria, horizontal gene transfer (HGT) is the main mechanism for acquiring ARGs. With the development of high-throughput sequencing, ARG sequence analysis is now feasible and widely available. Preventing the spread of AMR in the environment requires the implementation of ARGs mapping. The metagenomic technique, in particular, has helped in identifying antibiotic resistance within microbial communities. Due to the exponential growth of experimental and clinical data, significant investments in computer capacity, and advancements in algorithmic techniques, the application of machine learning (ML) algorithms to the problem of AMR has attracted increasing attention over the past five years. The review article sheds a light on the application of bioinformatics for the antibiotic resistance monitoring. The most advanced tool currently being employed to catalog the resistome of various habitats are metagenomics and metatranscriptomics. The future lies in the hands of artificial intelligence (AI) and machine learning (ML) methods, to predict and optimize the interaction of antibiotic-resistant compounds with target proteins.

, able to survive on the surfaces of medical devices, is a life-threatening pathogen that mainly leads to nosocomial infection especially in immunodeficient and cystic fibrosis (CF) patients. The antibiotic resistance in has become a world-concerning problem, which results in reduced and ineffective therapy efficacy. Besides intrinsic properties to decrease the intracellular content and activity of antibiotics, develops acquired resistance by gene mutation and acquisition, as well as adaptive resistance under specific situations. With in-depth research on drug resistance mechanisms and the development of biotechnology, innovative strategies have emerged and yielded benefits such as screening for new antibiotics based on artificial intelligence technology, utilizing drugs synergistically, optimizing administration, and developing biological therapy. This review summarizes the recent advances in the mechanisms of antibiotic resistance and emerging treatments for combating resistance, aiming to provide a reference for the development of therapy against drug-resistant .

is a versatile Gram-negative pathogen known for its ability to invade the respiratory tract, particularly in cystic fibrosis patients. This review provides a comprehensive analysis of the multifaceted strategies for colonization, virulence, and immune evasion used by to infect the host. We explore the extensive protein arsenal of , including adhesins, exotoxins, secreted proteases, and type III and VI secretion effectors, detailing their roles in the infective process. We also address the unique challenge of treating diverse lung conditions that provide a natural niche for on the airway surface, with a particular focus in cystic fibrosis. The review also discusses the current limitations in treatment options due to antibiotic resistance and highlights promising future approaches that target host-pathogen protein-protein interactions. These approaches include the development of new antimicrobials, anti-attachment therapies, and quorum-sensing inhibition molecules. In summary, this review aims to provide a holistic understanding of the pathogenesis of in the respiratory system, offering insights into the underlying molecular mechanisms and potential therapeutic interventions.

, a resilient bacterium in diverse food conditions, such as refrigeration, reduced water activity and low pH, poses a significant threat to the food industry and public health. In recent years, it has been documented an increase in the antibiotic resistance of zoonotic pathogens, including . This review provides new insight into the molecular mechanisms involved in both intrinsic and acquired antibiotic resistance of with an emphasis on the effect of different environmental and food-related factors. It also explores the relationship of these resistance mechanisms with virulence factors. An analysis of literature data (2009-2021) was conducted to investigate statistically and graphically potential associations between specific antibiotic resistance patterns in the pathogen and food categories using an unbiased variance analysis. The results evidenced that food type had an influence on the antibiotic resistance profiles of , with meat and vegetables being the food categories exhibiting the most prevalent profiles. The frequent detection of resistance to ampicillin, penicillin, and tetracycline (non-intrinsic resistances) indicates that specific processing conditions along the food chain may induce them. Many questions remain about the impact of food chain factors (e.g. thermal treatments, cold chain, preservatives, etc.) and food type (low pH, reduced water activity, etc.) on the antibiotic resistance patterns of the pathogen, particularly concerning food-related sources, the resistance mechanisms involved (e.g. cross-protection, horizontal gene transfer, etc.), and the evolutionary processes of antibiotic-resistant microbial populations. Metagenomics, in addition to other -omics technologies (metabolomics and transcriptomics), allows a better understanding of the processes involved in the acquisition of resistance.

infections, particularly invasive candidiasis, pose a serious global health threat.  is the most prevalent species causing candidiasis, and resistance to key antifungal drugs, such as azoles, echinocandins, polyenes, and fluoropyrimidines, has emerged. This growing multidrug resistance (MDR) complicates treatment options, highlighting the need for novel therapeutic approaches. Antifungal peptides (AFPs) are gaining recognition for their potential as new antifungal agents due to their diverse structures and functions. These natural or recombinant peptides can effectively target fungal virulence and viability, making them promising candidates for future antifungal development. This review examines infections caused by  species, the limitations of current antifungal treatments, and the therapeutic potential of AFPs. It emphasizes the importance of identifying novel AFP targets and their production for advancing treatment strategies. By discussing the therapeutic development of AFPs, the review aims to draw researchers' attention to this promising field. The integration of knowledge about AFPs could pave the way for novel antifungal agents with broad-spectrum activity, reduced toxicity, targeted action, and mechanisms that limit resistance in pathogenic fungi, offering significant advancements in antifungal therapeutics.

Non-tuberculous mycobacteria (NTM) are opportunistic pathogens ubiquitous in the environment. is a relatively new pathogen associated with underlying lung chronic pathologies, accounting for most of the pulmonary infections linked to the rapidly growing mycobacteria group. This includes chronic obstructive pulmonary disease, bronchiectasis, or cystic fibrosis. Patient outcomes from infections are poor due to complicated treatments and other factors. Intrinsic drug resistance plays an important role. The toolbox of resistance is varied leading to complex strategies for treatment. Mechanisms include waxy cell walls, drug export mechanisms, and acquired resistance. Many studies have also shown the impact of extracellular DNA found in the biofilm matrix during early infection and its possible advantage in pathogenicity. In this review, we discuss the current knowledge of early infection focusing on biofilm formation, an environmental strategy, and which treatments prevent its formation improving current antibiotic treatment outcomes in preliminary studies.

Antimicrobial resistance (AMR) has been recognized as an important health crisis in the twenty first century. Type IV secretion systems (T4SSs) play key roles in the dissemination of AMR plasmids. Novel strategies that combat AMR problem by targeting T4SS sprung up in recent years. Here, we focus on the strategy of male-specific phages that could target and kill bacteria carrying conjugative AMR plasmids encoding T4SSs. We reviewed the recent advances in male-specific phages, including anti-conjugation mechanisms, clinical isolation and identification methods, classification and characteristics, and anti-conjugation efficacy and improving strategies. Male-specific phages constitute exciting candidates for developing sustainable anti-resistance biocontrol applications.

Procyanidins (PCs) have emerged as agents with potential antimicrobial and antibiofilm activities, although their mechanisms of action and structure-activity relationships remain poorly understood. This review assessed the potential mechanisms of action and applications of these compounds to explore these aspects. Studies on the antimicrobial properties of PCs suggest that they are involved in osmotic imbalance, DNA interactions and metabolic disruption. Although less studied, their antibiofilm activities include antiadhesive effects and the modulation of mobility and quorum sensing. However, most research has used uncharacterized plant extracts for assays, limiting the understanding of the structure-activity relationships of PCs and their mechanisms. Clinical trials on the antimicrobial and antibiofilm properties of PCs have not clarified these issues due to nonstandardized methodologies, inadequate chemical characterization, and the limited number of studies, preventing a consensus and evaluation of the effects. Additionally, patent analysis revealed that technological developments in the antimicrobial and antibiofilm uses of PCs are concentrated in health care and dental care, but new biotechnological uses are emerging. Therefore, while PCs are promising antimicrobial and antibiofilm compounds, further research into their chemical structures and mechanisms of action is crucial for evidence-based applications in biotechnology and health care.

(PA), an opportunistic human pathogen that is frequently linked with chronic infections in immunocompromised individuals, is also metabolically versatile, and thrives in diverse environments. Additionally, studies report that PA can interact with other microorganisms, such as bacteria, and fungi, producing unique metabolites that can modulate the host immune response, and contribute to disease pathogenesis. This review summarizes the current knowledge related to the metabolic interactions of PA with other microorganisms (, , , , and ) and human hosts, and the importance of these interactions in a polymicrobial context. Further, we highlight the potential applications of studying these metabolic interactions toward designing better diagnostic tools, and therapeutic strategies to prevent, and treat infections caused by this pathogen.

Pathogen detection is increasingly applied in medical diagnosis, food processing and safety, and environmental monitoring. Rapid, sensitive, and accurate pathogen quantification is the most critical prerequisite for assessing protocols and preventing risks. Among various methods evolved, those based on clustered regularly interspaced short palindromic repeats (CRISPR)-associated proteins (Cas) have been developed as important pathogen detection strategies due to their distinct advantages of rapid target recognition, programmability, ultra-specificity, and potential for scalability of point-of-care testing (POCT). However, arguments and concerns on the quantitative capability of CRISPR-based strategies are ongoing. Herein, we systematically overview CRISPR-based pathogen quantification strategies according to the principles, properties, and application scenarios. Notably, we review future challenges and perspectives to address the of precise pathogen quantification by CRISPR-Cas. We hope the insights presented in this review will benefit development of CRISPR-based pathogen detection methods.

Dental caries, as a biofilm-related disease, is closely linked to dysbiosis in microbial ecology within dental biofilms. Beyond its impact on oral health, bacteria within the oral cavity pose systemic health risks by potentially entering the bloodstream, thereby increasing susceptibility to bacterial endocarditis, among other related diseases. , a principal cariogenic bacterium, possesses virulence factors crucial to the pathogenesis of dental caries. Its ability to adhere to tooth surfaces, produce glucans for biofilm formation, and metabolize sugars into lactic acid contributes to enamel demineralization and the initiation of carious lesions. Its aciduricity and ability to produce bacteriocins enable a competitive advantage, allowing it to thrive in acidic environments and dominate in changing oral microenvironments. In contrast, commensal streptococci, such as , , and , act as primary colonizers and compete with for adherence sites and nutrients during biofilm formation. This competition involves the production of alkali, peroxides, and antibacterial substances, thereby inhibiting growth and maintaining microbial balance. This dynamic interaction influences the balance of oral microbiota, with disruptions leading to shifts in microbial composition that are marked by rapid increases in abundance, contributing to the onset of dental caries. Thus, understanding the dynamic interactions between commensal and pathogenic bacteria in oral microecology is important for developing effective strategies to promote oral health and prevent dental caries. This review highlights the roles and competitive interactions of commensal bacteria and in oral microecology, emphasizing the importance of maintaining oral microbial balance for health, and discusses the pathological implications of perturbations in this balance.

Frequent viral infections leading to infectious disease outbreaks have become a significant global health concern. Fully elucidating the molecular mechanisms of the immune response against viral infections is crucial for epidemic prevention and control. The innate immune response, the host's primary defense against viral infection, plays a pivotal role and has become a breakthrough in research mechanisms. A component of the innate immune system, damage-associated molecular patterns (DAMPs) are involved in inducing inflammatory responses to viral infections. Numerous DAMPs are released from virally infected cells, activating downstream signaling pathways internal and external receptors on immune cells. This activation triggers immune responses and helps regulate viral host invasion. This review examines the immune regulatory mechanisms of various DAMPs, such as the S100 protein family, high mobility group box 1 (HMGB1), and heat shock proteins, in various viral infections to provide a theoretical basis for designing novel antiviral drugs.

is a Gram-negative anaerobic bacterium that is a common pathogen of periodontitis. Recent studies have revealed that is closely associated with a variety of diseases involving multiple systems. Under the action of its virulence factors such as cysteine protease and adhesins, has the ability to bind and invade various host cells including gingival fibroblasts. It can also copolymerize a variety of pathogenic bacteria, leading to interference with the host's immune inflammatory response and causing various diseases. In this article, we review the progress of research on virulence factors and bacterial pathogenesis, and the correlation between and various diseases.

Biofilms represent resilient microbial communities responsible for inducing chronic infections in human subjects. Given the escalating challenges associated with antibiotic therapy failures in clinical infections linked to biofilm formation, a peptide-based approach emerges as a promising alternative to effectively combat these notoriously resistant biofilms. Contrary to conventional antimicrobial peptides, which predominantly target cellular membranes, antibiofilm peptides necessitate a multifaceted approach, addressing various "biofilm-specific factors." These factors encompass Extracellular Polymeric Substance (EPS) degradation, membrane targeting, cell signaling, and regulatory mechanisms. Recent research endeavors have been directed toward assessing the potential of peptides as potent antibiofilm agents. However, to translate these peptides into viable clinical applications, several critical considerations must be meticulously evaluated during the peptide design process. This review serves to furnish an all-encompassing summary of the pivotal factors and parameters that necessitate contemplation for the successful development of an efficacious antibiofilm peptide.

The rapid increase of antibiotic-resistant pathogens is severely limiting our current treatment possibilities. An important subset of the resistance mechanisms conferring antibiotic resistance have public effects, allowing otherwise susceptible bacteria to also survive antibiotic treatment. As susceptible bacteria can survive treatment without bearing the metabolic cost of producing the resistance mechanism, there is potential to increase their relative frequency in the population and, as such, select against resistant bacteria. Multiple studies showed that this altered selection for resistance is dependent on various environmental and treatment parameters. In this review, we provide a comprehensive overview of their most important findings and describe the main factors impacting the selection for resistance. In-depth understanding of the driving forces behind selection can aid in the design and implementation of alternative treatments which limit the risk of resistance development.

In recent times, the nasal region has emerged as a distinctive and dynamic environment where a myriad of microbial communities establish residence from infancy, persisting as both commensal and opportunistic pathogens throughout the lifespan. Understanding the coexistence of microorganisms in respiratory mucosal layers, their potential for infections, and the underlying molecular mechanisms shaping these interactions is crucial for developing efficient diagnostic and therapeutic interventions against respiratory and neurodegenerative diseases. Despite significant strides in understanding the olfactory system's nexus with nasal microbiota, comprehensive correlations with neurological diseases still need to be discovered. The nasal microbiome, a sentinel in immune defense, orchestrates a delicate equilibrium that, when disrupted, can precipitate severe respiratory infections, including Chronic Rhinosinusitis, Chronic obstructive pulmonary disorder (COPD), and Asthma, and instigate a cascade effect on central nervous system diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Multiple sclerosis (MS). This review aims to redress this imbalance by meticulously exploring the anatomical and microbiological nuances of the nasal mucosal surface in health and disease. By delineating the molecular intricacies of these interactions, this review unravels the molecular mechanisms that govern the intricate nexus between nasal microbiota dysbiosis, olfactory dysfunction, and the progression of respiratory and neurological diseases.

Mycotoxin contamination of food and feed is a major global concern. Chronic or acute dietary exposure to contaminated food and feed can negatively affect both human and animal health. Contamination occurs through plant infection by toxigenic fungi, primarily and spp., either before or after harvest. Despite the application of various management strategies, controlling these pathogens remains a major challenge primarily because of their ability to adapt to environmental changes and selection pressures. Understanding the genetic structure of plant pathogen populations is pivotal for gaining new insights into their biology and epidemiology, as well as for understanding the mechanisms behind their adaptability. Such deeper understanding is crucial for developing effective and preemptive management strategies tailored to the evolving nature of pathogenic populations. This review focuses on the population-level variations within the two most economically significant toxigenic fungal genera according to space, host, and pathogenicity. Outcomes in terms of migration patterns, gene flow within populations, mating abilities, and the potential for host jumps are examined. We also discuss effective yet often underutilized applications of population genetics and genomics to address practical challenges in the epidemiology and disease control of toxigenic fungi.

Infection with induces chronic gastric inflammation, progressing to peptic ulcer and stomach adenocarcinoma. Macrophages function as innate immune cells and play a vital role in host immune defense against bacterial infection. However, the distinctive mechanism by which evades phagocytosis allows it to colonize the stomach and further aggravate gastric preneoplastic pathology. exacerbates gastric inflammation by promoting oxidative stress, resisting macrophage phagocytosis, and inducing M1 macrophage polarization. M2 macrophages facilitate the proliferation, invasion, and migration of gastric cancer cells. Various molecular mechanisms governing macrophage function in the pathogenesis of infection have been identified. In this review, we summarize recent findings of macrophage interactions with infection, with an emphasis on the regulatory mechanisms that determine the clinical outcome of bacterial infection.