Pore-forming toxins (PFTs) are essential virulence factors produced by many bacterial pathogens, enabling tissue invasion, nutrient acquisition, and immune evasion. Neutralizing these toxins offers a promising therapeutic avenue to mitigate infection symptoms and slow disease progression. Recent research highlights the potential of host-inspired strategies targeting toxin-membrane interactions. Statins and oxysterols disrupt intracellular cholesterol synthesis and trafficking to reduce its abundance in cell membranes, mimicking natural cellular defenses against PFTs. Aminosterols alter membrane properties to hinder toxin binding and pore formation. Nanoparticle-based decoys, such as artificial liposomes composed of the lipids cholesterol and sphingomyelin or recycled cell membranes, act as toxin traps, sequestering PFTs to protect host tissues. These nanoparticles demonstrate broad-spectrum efficacy across many bacterial species and offer additional functions, such as scavenging inflammatory cytokines. This review evaluates the clinical potential of these emerging treatment strategies and discusses the advantages of leveraging host factors to mitigate bacterial virulence rather than directly targeting toxins. Such host-inspired approaches represent a novel and complementary addition to the arsenal against antibiotic-resistant bacterial pathogens.
Maintaining body temperature is critical, with brown adipose tissue (BAT) and uncoupling protein 1 (UCP1) activation playing pivotal roles in heat generation and metabolism. Modulating thermoregulation pathways in BAT can help alleviate fever, enhance metabolic well-being, and boost immune function during viral infections such as influenza A. This review explores the intricate link between thermogenesis and influenza A virus (IAV), highlighting how IAV impacts body temperature regulation and immune responses. Mitochondria's functions in energy production, heat generation, and UCP1-mediated thermogenesis underscore their significance in regulating body temperature, metabolic rate, and responsiveness to environmental cues like cold exposure. Understanding the interplay among mitochondria, UCP1, and thermoregulation offers insights for potential therapeutic interventions in managing IAV infections. The regulatory mechanisms governing thermogenesis influence adipose tissue thermogenesis through various pathways, affecting body temperature and metabolic functions. Additionally, the review underscores potential therapeutic targets within thermogenesis pathways associated with IAV infection and their regulatory mechanisms to improve prevention and treatment strategies. This review underscores the pivotal role of thermogenesis and mitochondrial function in the host's response to IAV infections, emphasizing the need for further research to enhance management strategies.
The human gut microbiome is increasingly recognized as a key modulator of health and disease, with growing evidence supporting its influence on responses to cancer therapy. An important aspect of this relationship is gut microbial resilience, defined as the ability of the microbiome to recover its ecological equilibrium following disruption. Individual variations in microbial composition significantly influence resilience and, consequently, personalized responses to cancer treatments. However, the underlying functional characteristics of a resilient microbiome remain incompletely understood. Identifying specific microbial profiles with greater resilience to cancer therapies could improve the ability to predict treatment responses and mitigate adverse events. However, despite growing interest, a lack of longitudinal and mechanistic studies currently limits their clinical translation. This review examines current literature on gut microbiome compositions and individual treatment response to cancer therapy, with a focus on microbial features linked to resilience which could enable prediction of adverse response. While the use of microbial metabolites as predictive biomarkers (e.g. short-chain fatty acids and bile acids) is promising, further longitudinal and interventional studies are essential to support clinical application. Establishing specific microbial and metabolite profiles that promote resilience is essential to advance this emerging field of personalized gut-microbiome therapy. Gut microbiome influences cancer development, treatment response, and outcomes.Microbial metabolites such as SCFAs and bile acids regulate host physiology and immunity.Cancer therapies disrupt the microbiome, driving variability in adverse events among patients.Baseline microbial composition may predict occurrence of treatment-induced toxicities.Identifying resilient profiles could enable microbiome-based interventions.
Bacteria, present in normal conditions in the microbiome or during infections, exert profound effects on genome stability, with both genotoxic and genoprotective consequences. Certain pathogenic bacteria, such as Escherichia coli (colibactin-producing strains), Helicobacter pylori, Fusobacterium nucleatum, and Campylobacter jejuni, induce DNA damage and are implicated in cancer development through direct toxin production, chronic inflammation, immune modulation, and disruption of host cell signaling. Genotoxins such as colibactin, the cytolethal distending toxin, and the typhoid toxin induce DNA double-strand breaks, chromosomal instability, and impair DNA repair pathways, contributing to carcinogenesis. These effects occur upon gastrointestinal, urogenital, systemic (sepsis), and neurological (meningitis) infections, in both humans and animals. Conversely, commensal and probiotic bacteria, notably Lactobacillus and Bifidobacterium species, play a protective role by reducing oxidative DNA damage, modulating immune responses, and enhancing DNA repair. Their beneficial actions are partly mediated by metabolites such as short-chain fatty acids (e.g. butyrate), which influence gene regulation, apoptosis, and mucosal health. Probiotic bacteria can mitigate the genotoxic effects of dietary and bacterial toxins, offering a potential preventive strategy against genome instability and cancer. This review highlights the dualistic nature of bacterial influence on host genome integrity and underscores the importance of maintaining microbial balance.
The complex interaction between Aspergillus and Bacillus has been gaining attention with the evolution of their co-culture applications. Information reported on this interaction from different points of view including both synergistic and antagonistic mechanisms necessitates a review for better understanding. This review focuses on the interaction, biofilm formation, and the diverse biotechnological applications of Aspergillus and Bacillus, giving special attention to Aspergillus niger and Bacillus subtilis. The review demonstrates that co-cultivation of Aspergillus and Bacillus exhibits significant transcriptional changes, impacting metabolism and secondary metabolite production in both organisms. Signaling from living fungal hyphae, EPS production, TasA fibrils, and regulators like Spo0A are essential in forming biofilm communities. Nutrient availability and pH levels, species type, and mutations in EPS-producing genes may also influence whether Bacillus will act antagonistically or synergistically with Aspergillus. This dual-nature complex interaction activates silent genes synthesizing novel compounds mainly with antifungal and medicinal properties, showcasing its potential for diverse applications in various fields such as agriculture and crop protection, bioremediation, environmental biotechnology, food science and fermentation, industrial biotechnology, and medical biotechnology and health. The use of Aspergillus and Bacillus species has evolved from simple monoculture applications to more sophisticated co-cultures and has been trending toward their synergy and metabolic optimization. Bacillus can either inhibit growth or engage in biofilm with AspergillusAspergillus–Bacillus co-cultivation produces novel secondary metabolitesThe metabolites can inhibit or promote Aspergillus depending on the environmentCross-feeding of Aspergillus and Bacillus alters their growth and gene regulationTheir interaction offers applications in food science, environment, medicine, etc.
Porphyrins, their derivatives, and metal ion complexes - particularly copper-substituted forms such as Cu-Chl, Cu-Chln, and Na-Cu-Chln - are increasingly recognized for their broad-spectrum antimicrobial properties. However, in the context of terminological and trivial confusions in food chemistry and pharmaceuticals, data on the chemical properties and biological activity of porphyrins remains fragmented and lacks comprehensive systematization. This review adopts a cross-disciplinary mapping approach to clarify the chemical structures, nomenclature, antimicrobial properties, and the presented mechanistic insights of porphyrins and their derivatives, highlighting their significance in both the food and pharmaceutical industries. As a result of the mapping systematization, porphyrins have been remarked as current and potential antimicrobial agents, with a specific emphasis on the compounds such as Cu-Chl, Cu-Chln, and Na-Cu-Chln. Copper complexation has been shown to enhance biological activity while maintaining low toxicity profiles. Emphasis is placed on Cu-Chl, Cu-Chln, and Na-Cu-Chln, which demonstrate promising properties and applications in nutraceuticals and therapeutics. Their bactericidal properties, which resulted in combating antibiotic-resistant infection-causative pathogens, are particularly interesting, especially in the era of addressing global challenges such as antibiotic resistance. This conceptual review remarks on the critical gaps in current knowledge and accentuates the need for systematic studies to optimize the clinical and industrial applications of porphyrins.
Helicobacter pylori (H. pylori) infection is a common and serious infectious disease that requires eradication as it is the primary cause of gastric adenocarcinoma. However, the growing prevalence of antibiotic resistance, severe side effects, and the inability of current treatments to effectively address biofilm-embedded, intracellular, and dormant H. pylori strains, alongside their long-term gut microbiome disruptions, have rendered standard therapies increasingly ineffective. This predicament underscores the pressing need to explore antibiotic-independent antimicrobial moieties. This pursuit involves a multifaceted approach, encompassing innovative strategies that target critical regulatory points in H. pylori infection. These include the development of urease inhibitors, anti-adhesion therapies, treatments for intracellular H. pylori, strategies for eradicating dormant forms, interventions against biofilm formation, among others. Additionally, various antibiotic-independent antimicrobial moieties that can target multiple bacterial mechanisms and forms are being explored, such as intraluminal photoacoustic therapy, the use of nanoparticles, antimicrobial peptides (AMPs), vaccines, phage therapy, and other cutting-edge treatments. These strategies offer promising prospects for non-antibiotic treatments to overcome this persistent and often debilitating infection.
Bacterial vaginosis (BV), first identified in the 1950s, is a common vaginal condition characterized by a thin, homogeneous discharge with a fishy odor and minimal inflammation. Its high recurrence rate and associated complications pose significant challenges to patients' physical and mental health. Untreated, BV can result in severe outcomes, including pelvic inflammatory disease and adverse pregnancy complications. A comprehensive understanding of BV's diagnostic criteria, complications, drug resistance, and treatment strategies is essential for improving patient care. This review examines the vaginal microbiome, emphasizing the protective role of healthy flora through physical and immunological mechanisms. Key diagnostic methods, including Amsel's criteria, the Nugent scoring system, BV Blue test, qPCR, and advanced techniques like 16S rRNA sequencing, are discussed. The review also explores the adverse outcomes of BV, such as increased risk of sexually transmitted infections, pregnancy-related complications, and social and psychological impacts. Finally, we highlight advancements in treatment, focusing on polymicrobial biofilms and combination therapies. Emerging approaches include standard antibiotics, probiotics, biofilm-targeting strategies, hormone replacement therapy, and partner treatment. This review underscores the importance of maintaining vaginal microbial balance and offers a detailed perspective on BV's mechanisms, diagnosis, and therapeutic innovations.
Since the 19th-century industrial revolution, Crohn's disease (CD), a chronic inflammatory bowel condition, has gained increasing recognition in both medical and public spheres. This review aims to critically analyze the integration of multi-omics data-encompassing genomics, transcriptomics, proteomics, and metabolomics-with network pharmacology to uncover the complex therapeutic mechanisms of Traditional Chinese Medicine (TCM) interventions for CD. By examining multi-omics profiles from CD patients treated with specific TCM formulations or their active components, network pharmacology can effectively pinpoint key biological pathways and molecular targets influenced by TCM. These pathways include, but are not limited to, the regulation of gut microbiota composition, modulation of inflammatory cytokine networks (such as TNF-α and IL-17), and the restoration of intestinal mucosal integrity. This integrated methodology not only aids in identifying active constituents but also facilitates the prediction of synergistic effects and clarifies the molecular interactions within TCM. Consequently, it establishes a solid framework for rational drug discovery and the formulation of personalized therapeutic strategies for CD. The primary focus of this review will be to explore the mechanisms and therapeutic potential of TCM for CD through the lens of network pharmacology, emphasizing its application in addressing this complex condition.
Bacterial protein kinases regulate fundamental processes like cell division and transcription, hence controlling various metabolic pathways. They share a common evolutionary origin with eukarya and archaea. Kinases promote the virulence of pathogenic bacteria and are also involved in the host-pathogen interactions leading to the manipulation of host defence systems for the establishment of infections. Bacterial protein kinases regulate various metabolic processes, including pathogenesis, virulence, upregulation of efflux pumps to discard antibiotics, synthesis of capsular polysaccharides, and pathogenesis. Bacterial kinases offer a new aspect of monitoring and managing the infections caused by bacterial pathogens. As kinases are essential proteins of the bacterial system, there are lesser chances of mutation in them. Hence, therapeutics targeting the pathogenic bacterial kinases would have significant value. This review deals with the functions and structural aspects of bacterial protein kinases, and the different types of kinase inhibitors that have been experimentally validated to control infections. They represent promising therapeutic target, as they will minimize the risk of gaining new types of resistance and offer a high probability of success, given their role as master regulators of the fundamental processes of the bacterial system.
Autophagy is a vital component of the host cell intracellular defense arsenal, culminating in the fusion of autophagosomes with lysosomes to degrade invading pathogens. While autophagosome formation has been extensively studied, recent insights reveal that the final fusion step constitutes a critical immunological bottleneck that is highly vulnerable to microbial sabotage. In this review, we synthesize evidence from diverse pathogens, including Mycobacterium tuberculosis, Salmonella enterica, Treponema pallidum, Helicobacter pylori, Coxiella burnetii, Yersinia pestis, and Porphyromonas gingivalis, demonstrating that autophagosome-lysosome fusion blockade is not incidental but represents a convergently evolved immune evasion strategy. We dissect three mechanistic strategies employed by these pathogens: disruption of RAB GTPases, interference with the HOPS and SNARE complexes, and inhibition or misregulation of lysosomal biogenesis and positioning. Each strategy targets the fusion machinery with remarkable specificity, often hijacking host regulatory circuits. We further discuss how these insights inform therapeutic interventions aimed at restoring autophagic flux. Fusion arrest emerges as a unifying hallmark of pathogen survival, positioning autophagosome-lysosome fusion as a critical frontier in the host-pathogen conflict. We advocate a paradigm shift from studying autophagy initiation markers to evaluating fusion competence as a functional measure of autophagic immunity.
Industrialization marked a significant turning point that impacted the global climate at an unprecedented scale. Oceans, covering 71% of the surface of Earth, play a pivotal role in regulating climate change factors, serving as essential components of planetary processes. In these oceanic ecosystems, marine bacteria are intricately involved in regulating various biogeochemical cycles that are crucial to climate regulation and ecosystem functioning. However, the ongoing climatic changes pose significant challenges to marine bacteria and their associated processes. In the Anthropocene epoch, the interaction between anthropogenic pollutants and climatic stressors further amplifies their impact on marine bacteria across diverse ecological niches and their resilience mechanisms. It delves into the interactive effects of anthropogenic pollutants with climatic stressors on bacteria, particularly emphasizing on organic pollutants, heavy metals, and microplastics. The review entails the impact and resilience mechanisms of marine bacteria in response to climatic stressors. The current trajectory of climatic changes highlights the urgent need for concerted global action to mitigate greenhouse gas emissions and adapt to the inevitable impacts of climate change. In this context, various strategies employing marine bacteria in mitigating climate change for a sustainable future have also been discussed.
Influenza viruses are highly contagious respiratory pathogens that cause seasonal outbreaks, leading to millions of infections and a significant number of deaths worldwide. To support rapid replication and transmission, influenza viruses hijack the host's metabolic pathways, including those involved in carbohydrate, amino acid, and lipid metabolism. Through this metabolic reprogramming, the virus leverages the host's metabolic resources to produce viral components and create specialized compartments necessary for replication and dissemination. In response, host cells activate a range of metabolic defense mechanisms to detect and counteract the virus-induced metabolic changes, resulting in a dynamic interplay that profoundly impacts the outcome of the infection. Advances in metabolomics have provided valuable insights into these complex host-virus interactions, identifying key metabolic biomarkers with potential for early diagnosis, real-time disease monitoring, and therapeutic response evaluation, especially in the early detection and management of severe influenza infections. In the future, these metabolic biomarkers could drive the development of new strategies for influenza prevention and treatment, providing a scientific foundation for precision medicine.
Picobirnaviruses (PBVs) are double-stranded RNA viruses detected in various environments and host-associated samples, including those from humans, non-human animals, invertebrates and birds. First described in human fecal material, PBVs were initially hypothesized to be human enteric pathogens. However, no definitive association with disease has been established. Their pathogenic potential remains unclear, therefore, their presence in clinical or environmental samples may reflect asymptomatic colonization, indirect association or infection of a non-human host. The PBV genome exhibits remarkably high genetic diversity both within and across its genomic segments, as well as notable variability in genetic code usage. Some PBV genomes use alternative codon assignments, raising the possibility that they infect prokaryotic or otherwise unconventional hosts. This review critically examines the experimental and bioinformatic methods used to detect PBVs and infer their host range. We distinguish between methods used for PBV genome identification (e.g. PCR, metagenomic sequencing) and those aimed at host determination (e.g. culturing attempts, codon usage bias, cloning into model systems). We also evaluate the challenges and limitations associated with each approach. Elucidating PBVs' host range is essential to understanding their biological roles and ecological significance, including potential implications for human and animal health and microbial community dynamics across ecosystems.
The Flaviviridae family includes many medically relevant members, such as dengue, Zika, West Nile, and hepatitis C viruses, that produce hundreds of millions of infections annually. There is a close relationship between these infections and inflammation triggering as an important part of the host's immune response and of pathogenesis. These inflammatory processes are mediated by the activation of multiprotein complexes known as inflammasomes. Several inflammasomes have been described which differ in their composition and their activating stimuli. The NLRP3 inflammasome is the most studied. Its activation begins by the recognition of pathogen-associated molecular patterns such as viral RNA, potassium efflux, calcium flux, increased reactive oxygen species; and culminates in the maturation and secretion of pro-inflammatory cytokines such as IL-1β and IL-18, and cell death by pyroptosis. This review summarizes the most relevant aspects of NLRP3 inflammasome activation in relevant flavivirus infections from clinical and laboratory studies in biological models. Understanding the activation, mounting, and regulation of the inflammatory response during viral infections is a poorly exploited area of opportunity for the development of efficient and safe treatment strategies, which could include NLRP3 inflammasome inhibition.
Crohn's disease (CD) is a chronic inflammatory bowel disease becoming a major issue for healthcare systems in most parts of the world. While the causes of the disease are still not fully understood, the role of the microbiota has been widely demonstrated including the colonization by a particular pathovar of Escherichia coli, defined as adherent and invasive E. coli (AIEC), able to adhere to, and invade the intestinal epithelium, as well as to survive within macrophages. As the involvement of AIEC within CD pathophysiology is highly suspected, developing new strategies to limit AIEC colonization is a promising area of research. In this context, chitin and its derivatives, such as chitosan and chito-oligosaccharides (COS), possessing immunomodulatory and antimicrobial properties, could be promising candidates. This review provides a structural overview of chitin and its derivatives and summarizes the existing literature in the context of the potential beneficial effects of chitinous elements in CD and CD-like models, their capability to restrict AIEC colonization via multiple mechanisms, such as of reducing AIEC growth, countering biofilm formation, blocking bacterial adhesion, or stimulating the innate immune response. Lastly, we will explore strategies based on chitin-supplemented diet as therapeutic strategy in patients with CD.
Fungal infections pose a significant global health threat, particularly among immunocompromised individuals facing life-threatening complications. The severity of secondary fungal infections is driven by the expression of virulence factors in immunocompromised individuals. The COVID-19 pandemic has highlighted the susceptibility of immunocompromised patients to secondary fungal infections, prompting a closer examination of the underlying mechanisms. This review provides a comprehensive overview of the virulence mechanisms of major fungal pathogens (Aspergillus, Candida, and Mucorales) in COVID-19-associated secondary infections. The review systematically categorizes key virulence factors, including thermotolerance, adhesins, hydrolytic enzymes, mycotoxins, and biofilm formation, and explores their interplay with the host's immune status, particularly under corticosteroid therapy. Focusing on the intersection of fungal pathogenesis and COVID-19, the article examines molecular mechanisms underlying Aspergillus, Mucorales, and Candida pathogenicity, including iron metabolism, spore coat proteins, and immune evasion strategies. Followed by linking the molecular mechanisms to therapeutic strategies and clinical outcomes.
Thermophile research has been transformed over the past decade by advances in genome sequencing. Once centered on culture collections and physiological studies of terrestrial hot springs and deep-sea hydrothermal vents, the field now employs amplicon sequencing, shotgun metagenomics, and long-read platforms to reveal the diversity, ecology, and genomic potential of thermophiles. Metagenome-assembled genomes (MAGs), metatranscriptomes, and metaproteomes have become crucial for linking taxonomy with function, uncovering previously hidden microbial dark matter in heated ecosystems. Bioinformatics, increasingly integrated with machine learning, has expanded insights into microbial biology, biomolecules, and ecological interactions. These advances highlight the broader environmental significance of thermophiles, spanning fundamental roles in ecosystem processes to practical applications. In 2015, we published Thermophiles in the Genomic Era: Biodiversity, Science, and Application to capture early next-generation sequencing milestones. A decade later, with tremendous progress achieved, this review revisits the field by synthesizing recent advances across viruses, planktonic thermophiles, and biofilm communities, emphasizing the power of genome-resolved approaches. We also highlight overlooked areas, opportunities for ecological integration and predictive modeling, and the importance of translating discoveries into biotechnological innovation. Our aim is to provide young researchers with a roadmap of emerging questions and strategies likely to shape the next decade of thermophile research.
Although biofilms pose significant challenges in healthcare and in different industries, main antibiofilm agents currently used for surface disinfection and clinical applications often exhibit harmful side effects and contribute to the development of antimicrobial resistance. To tackle this challenge many biomolecules have been studied as alternatives, including bioemulsifiers, amphiphilic polymers that exhibit low toxicity and high biodegradability yet remain largely unexplored to date. By covering publications from 1983 to early 2025, this review aims to compile the current knowledge on bioemulsifiers from different microbial sources with a focus on their relevant properties as promising antibiofilm agents. Research on probiotics, often involving producer strains isolated from dairy products and animal microbiomes, focusing on marine-derived microorganisms were the most prominent fields benefiting from these molecules. Among different molecules, polysaccharides stood out, especially those from cultivable bacteria. This review focuses on key physico-chemical properties, such as their ability to alter surface hydrophobicity and to inhibit quorum sensing, while providing a comprehensive overview of their putative antibiofilm mechanisms. Finally, we highlight several identified bottlenecks and discuss key strategies and recent advances in metabolic and molecular engineering to instigate the research appetite on unlocking the full potential of microbial bioemulsifiers for biofilm control and prevention.
Acinetobacter baumannii (A. baumannii) has become a major hospital-acquired pathogen, well-known for its rapid development of resistance to multiple antibiotics. The rising incidence of antibiotic-resistant A. baumannii presents a significant global public health challenge. Gaining a deep understanding of the mechanisms behind this resistance is essential for creating effective treatment options. This comprehensive review explores the understanding of various antibiotic resistance mechanisms in A. baumannii. It covers intrinsic resistance, acquired resistance genes, efflux pumps, changes in outer membrane permeability, alterations in drug targets, biofilm formation, and horizontal gene transfer. Additionally, the review investigates the role of mobile genetic elements and the clinical implications of antibiotic resistance in A. baumannii infections. The insights provided may inform the development of new antimicrobial agents and the design of effective infection control strategies to curb the spread of multidrug-resistant (MDR) A. baumannii strains in healthcare environments. Unlike previous reviews, this study offers a more integrative perspective by also addressing the pathogen's environmental resilience, with particular emphasis on its resistance to desiccation and the formation of robust biofilms. It further evaluates both established and emerging therapeutic strategies, thereby expanding the current understanding of A. baumannii persistence and treatment.