Candidozyma auris has emerged as one of the most formidable fungal pathogens of the modern era, designated a critical priority pathogen by the World Health Organization due to its multidrug resistance, thermotolerance, and capacity to cause prolonged outbreaks in healthcare settings. Unlike most fungal pathogens, C. auris exhibits a remarkable tropism for human skin, where it persists asymptomatically, forms biofilm-like structures resistant to conventional antiseptics, and serves as a reservoir for nosocomial transmission. Invasive infections, particularly candidemia, carry mortality rates of 40-60% and disproportionately affect immunocompromised individuals and those with prolonged healthcare exposure. Six geographically distinct clades have been described, each differing in antifungal susceptibility, colonization capacity, and virulence. Despite the clinical urgency, the molecular and immunological mechanisms governing cutaneous colonization, persistence, and the transition to invasive infection remain poorly understood. This review examines the biology, virulence, and skin colonization dynamics of C. auris, with emphasis on experimental models (i.e. murine, porcine, and human skin systems) that have advanced our understanding of host-pathogen interactions, immune responses, and the efficacy of antifungal and decolonization strategies, highlighting critical knowledge gaps and future research priorities.
Oral polymicrobial biofilms formed between Candida albicans and bacterial pathogens underlie early childhood caries, denture stomatitis, periodontal disease, and oropharyngeal candidiasis, infections that conventional antimicrobials consistently fail to eradicate. The agglutinin-like sequence 3 (Als3) protein is a GPI-anchored hypha-specific adhesin that serves as the principal molecular scaffold for interkingdom co-aggregation in these biofilms. This review examines the molecular architecture and domain organization of Als3, including the N-terminal peptide-binding cavity (PBC) and the amyloid-forming region, as well as the regulatory network controlling ALS3 expression. The structural basis of Als3 interactions with staphylococcal MSCRAMMs, streptococcal antigen I/II adhesins, Porphyromonas gingivalis internalin InlJ, and Streptococcus mutans glucosyltransferases is examined in detail. Emergent properties of Als3-dependent oral co-biofilms, including elevated antimicrobial tolerance, architectural complexity, metabolic interdependence, and interkingdom signaling amplification, are analyzed. Therapeutic strategies reviewed include the NDV-3A recombinant vaccine, anti-Als3 monoclonal antibodies, peptide-based competitive inhibitors, and small-molecule antagonists that bind the Als3 N-terminal domain. Als3 acts at the interface between bacteria and fungi. Because of this, it is one of the few targets for which a single treatment can act on both the fungal and bacterial components of these hard-to-treat oral biofilms at once.
Quaternary ammonium compounds (QACs) are widely used disinfectants, favored for their broad antimicrobial action and safety profile. However, viral disinfection is complex and affected by multiple variables, including the virus's envelope status, exposure time, temperature, and organic matter presence. This has created considerable ambiguity in the literature.We searched PubMed and Scopus using terms including "quaternary ammonium compounds" and "virucidal," with a focus on only registered QACs (biocides), identifying 64 studies from 419 results. These studies examined viruses from 22 families (13 enveloped, 9 non-enveloped) across different experimental conditions.QACs are highly effective against enveloped viruses, even under suboptimal conditions, and remain relevant for pandemic response. However, proper cleaning protocols are essential to ensure complete virucidal activity. Against non-enveloped viruses, QAC effectiveness is less predictable. While Parvoviridae and Picornaviridae remain highly resistant, other families like Adenoviridae, Caliciviridae, and Sedoreoviridae show variable susceptibility depending on conditions. Adding synergistic agents such as acids or alkalis can improve QAC performance and mitigate this uncertainty.
The environmental accumulation of macroplastics has raised concerns regarding their role in the spread of antimicrobial resistance (AMR). As persistent and mobile substrates, macroplastics provide surfaces for microbial colonization and may act as reservoirs and vectors of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). However, their ecological significance remains insufficiently resolved. Following PRISMA guidelines, we conducted a systematic review of 55 peer-reviewed studies investigating environmentally collected and experimentally exposed macroplastics across marine, estuarine, and freshwater systems. Macroplastics consistently harbor clinically relevant ARB and ARGs, supporting their role as AMR reservoirs. However, evidence for systematic enrichment relative to surrounding matrices is inconsistent, and direct evidence of AMR transfer during environmental transport remains limited. Anthropogenic pressure, ecosystem type, and plastic weathering emerged as key drivers of AMR patterns, with freshwater systems typically showing higher abundance and diversity of ARB and ARGs. Weathering enhances biofilm development and the adsorption of selective agents, whereas the influence of polymer type remains inconclusive. Methodological heterogeneity, including inconsistent quantification strategies, limited environmental controls, and lack of phenotype-genotype linkage, constrains robust inference. We propose a standardized, integrative framework combining environmental baselines, harmonized AMR quantification, and functional validation to improve comparability and support reliable evaluation of macroplastic-associated AMR.
Emerging zoonoses often arise at wildlife-human interfaces, yet prevention efforts still treat wildlife reservoirs in isolation. This review synthesizes evidence on RNA viruses detected in bats and rodents across the Americas and examines the ecological interfaces underlying bat-rodent-human transmission. Rather than an exhaustive inventory, we adopt an interface-based perspective on cross-species transmission. We focus on astroviruses, coronaviruses, hantaviruses, and lyssaviruses-groups combining high genetic diversity, broad host ranges, and documented or suspected zoonotic potential. We describe interfaces created by land-use change, urbanization, shared food and water resources, co-roosting in human-made structures, environmental contamination (guano- and urine-borne aerosols), and seasonality of shedding. Key gaps include geographic sampling biases, limited infectivity data, and scarce integration of host movement, contact ecology, and human practices. Prevention priorities include longitudinal surveillance along rural-urban gradients, genomic tracking of cross-species transmission, experimental work on commensal rodents that may bridge bats and humans, and co-designed community interventions. Given the region's exceptional biodiversity and rapid socio-ecological change, the Americas represent a hotspot where bat-rodent-human viral interactions may increase spillover risk. Recognizing and monitoring this overlooked interface can sharpen early warning and inform cost-effective prevention.
Fungal infections represent a major global health challenge due to their high morbidity and mortality and calling for innovative therapeutic approaches. Effective redox regulation is essential for fungal pathogens to maintain viability and virulence within the oxidative environment of the host. Key components of the fungal antioxidant network include superoxide dismutases, catalases, glutathione- and thioredoxin-dependent systems, and enzymes involved in trehalose metabolism. In pathogens such as Candida albicans and Cryptococcus neoformans, disruption of specific antioxidant factors increases susceptibility to oxidative stress and markedly reduces virulence. Moreover, redox-sensing transcription factors such as Yap1, Cap1, and CnYap1 play central roles in modulating antioxidant response during host interaction and antifungal exposure. Cap1 is critical for oxidative stress tolerance and immune evasion in C. albicans, whereas CnYap1 is required for resistance to oxidative stress and fluconazole in C. neoformans. In addition, antifungals such as amphotericin B increase ROS load, demanding efficient antioxidant responses from fungal cells. Collectively, these findings highlight oxidative stress response pathways as a promising therapeutic target for invasive fungal infections. Targeting key elements of redox sensing and detoxification pathways, such as transcriptional regulators and antioxidant enzymes, could increase antifungal activity, compromise fungal resistance mechanisms, and ultimately improve clinical outcomes.
Antimicrobial resistance (AMR) is a major global public health threat, particularly in low- and middle-income countries. In Ecuador, AMR research has expanded during the last two decades, but evidence remains fragmented and largely restricted to the human health sector. We systematically reviewed studies reporting laboratory-confirmed bacterial resistance in Ecuador between 2000 and 2024, including evidence from human, animal, food, and environmental sources. Eighty studies met the inclusion criteria. Most were hospital-based and conducted in urban areas, with limited evidence from rural, Amazonian, and insular regions. Gram-negative bacteria accounted for the greatest resistance burden, particularly Escherichia coli (56.6%), Klebsiella pneumoniae, Salmonella spp. (22.3%), the Acinetobacter baumannii complex, and Pseudomonas aeruginosa, together with resistant Staphylococcus aureus and Mycobacterium tuberculosis. Resistance to beta-lactams and fluoroquinolones predominated, whereas carbapenem resistance was especially notable among WHO priority pathogens. Evidence from animal, food, and environmental sectors was scarce and heterogeneous, and molecular characterization was inconsistently reported. These findings highlight important surveillance gaps beyond hospital settings and underscore the need for integrated multisectoral surveillance to strengthen public health policy, antimicrobial stewardship, and AMR prevention in Ecuador.
Bacterial outer membrane vesicles (bOMVs) are nanoscale structures derived from Gram-negative (G-) bacteria that play an important role in oral diseases. As key mediators of host-microbe interactions, bOMVs contribute to the pathogenesis of periodontitis, oral squamous cell carcinoma (OSCC), and oral lichen planus (OLP) by disrupting immune homeostasis and promoting tissue destruction. Beyond the oral cavity, bOMVs serve as critical vectors in the oral-systemic axis, disseminating virulence factors to distant organs and contributing to atherosclerotic cardiovascular diseases (ACVDs), Alzheimer's disease (AD), and gastrointestinal (GI) disorders. Concurrently, their inherent properties, including cargo-loading capacity, immunogenicity, and biofilm penetration, position them as promising platforms for noninvasive diagnostics and targeted therapeutics. This review systematically integrates current knowledge on bOMVs biogenesis, pathogenic mechanisms in oral and systemic diseases, and emerging applications in diagnosis and treatment. We also highlight key challenges and future directions for translating bOMVs-based strategies into clinical practice, emphasizing their potential as next-generation theranostic tools (combining therapeutic and diagnostic functions) for oral diseases.
Medical biofilms are a significant problem in chronic diseases like diabetic ulcers that do not heal, infections of medical devices and CF. The extracellular polymeric matrix is a barrier to antibiotic penetration. In search of an alternative, approaches based on antimicrobial peptides (AMPs) and enzymes have been developed to tackle the multi-drug resistance. This review collates the existing literature on zoonotic and bacterial origin AMPs, along with the matrix-disrupting and quorum-quenching enzymes, highlighting those which have proven to be effective in vitro/in vivo against clinical isolates from patients. Enzymes (e.g. cellulase, alginate lyase, and dispersin B) can break down matrix components or block critical signaling molecules and can be seen to have strong synergy with antibiotics, whereas AMPs disrupt cell membranes and downregulate genes that encode biofilm-forming proteins. Our analysis reveals however, a key translational bottleneck: there were no clinical trials in human subjects identified despite strong preclinical evidence of activity. This review discusses these encouraging pre-clinical findings and identifies specific physiological and challenges that need to be overcome to take these alternative therapies to clinical practice.
Stress may be defined as a nonspecific systemic response that occurs when the body is engaged by a variety of stimuli, which has the capacity to influence a number of different physiological systems of the body. Recent research has shown that the microbiota that live in the gut are an essential part of human microecology and play a significant part in the process of preserving the health of the body. Through its influence on the functioning of the intestinal mucosal barrier, the intestinal immune system, and the motility of the gastrointestinal tract, stress has the ability to bring about dysbiosis in the gut. This narrative review investigates the changes that occur in the microbiota of the gut as a consequence of environmental stress and investigates the possible processes that may be involved.
Pathogenicity islands (PAIs) are horizontally acquired genomic regions that encode virulence factors essential for bacterial pathogenicity. Their expression must be precisely regulated to avoid detrimental fitness costs outside the host and to ensure timely activation during infection. This review explores how environmental cues such as temperature, osmolarity, pH, and nutrient availability regulate PAI gene expression via nucleoid-associated proteins (NAPs). Molecular mechanisms by which key NAPs, including H-NS, Fis, IHF, and HU, modulate PAI activity in response to environmental changes are examined. H-NS functions as a central xenogeneic silencer by repressing AT-rich PAI genes under non-host conditions through oligomerization and DNA bridging. Its activity is modulated by environmental inputs and post-translational modifications. In contrast, Fis promotes virulence gene expression during early exponential growth. IHF and HU serve as architectural DNA-bending proteins that facilitate transcriptional activation by altering local DNA topology or counteracting H-NS repression. These proteins integrate environmental signals with chromosomal structure to fine-tune PAI expression. A cohesive model is proposed in which NAPs act as environmental interpreters of the genome, linking chromatin architecture with adaptive virulence gene regulation. Understanding these mechanisms provides valuable insight into bacterial pathogenesis and potential targets for antimicrobial intervention.
Salmonella is one of the most common causes of foodborne illness worldwide. These infections, in turn, exert an impact on both industry and healthcare settings. Salmonella is the agent that causes salmonellosis, a gastroenteric infection. Outbreaks of salmonellosis commonly arise from the consumption of contaminated foods of animal origin, and on occasion, from exotic and companion animals. The genus consists of more than 2,600 serovars, with Salmonella Typhimurium and Salmonella Enteritidis being the most commonly isolated serovars which cause non-typhoidal infection in susceptible humans. Moreover, factors such as global trade, government policy and globalization have led to an increased emergence of atypical salmonellae. Current limited literature suggests that these emerging atypical Salmonella serovars pose a unique threat to human health due to their novel host adaptations, antimicrobial resistance profiles, epidemiology and infection sources. Thus, this paper aims to provide a short overview of the current knowledge of the taxonomy of selected atypical serovars as well as their epidemiology, virulence factors and the impact they pose on the One Health paradigm. The aim of this being to highlight the ever-increasing importance of focusing research upon these variant serovars due to their changing incidence and diverse attributes.
Giant viruses constitute a remarkable group of large double-stranded DNA (dsDNA) viruses distinguished by their exceptional structural complexity and genomic features. Their genomes can reach 2.8 Mb, encoding hundreds of proteins, and virion diameters up to 1.5 μm. They infect diverse eukaryotic hosts and establish viral factories within host cells. Virophages are small dsDNA viruses (17-34 kb; 50-75 nm) that parasitize giant viruses. These satellite viruses hijack giant virus replication machinery while suppressing giant virus progeny, benefiting the host cell and creating a parasitic-symbiotic dynamic. This review examines the tripartite relationship between host cells, giant viruses, and virophages (CVv systems), focusing on: (1) virus-host interactions in amebae, marine flagellates, and unicellular algae; (2) molecular mechanisms of these interactions; and (3) ecological and evolutionary implications. We also identify current research challenges and propose future directions, particularly the molecular basis of viral interactions in CVv systems.
Klebsiella pneumoniae has emerged as a major global health threat, contributing significantly to neonatal sepsis, childhood mortality, and antibiotic-resistant hospital-acquired infections. The World Health Organization (WHO) recently reported the widespread detection of hypervirulent K. pneumoniae (hvKP) strains carrying carbapenem resistance genes across all WHO regions, prompting a formal warning from the Global Antimicrobial Resistance Surveillance System. Despite growing concerns, the mechanisms driving the enhanced pathogenicity and adaptability of these strains remain incompletely understood. Recent research has uncovered novel virulence factors and elucidated key adaptations enabling K. pneumoniae to thrive in diverse host tissues. This review synthesizes current knowledge on K. pneumoniae pathogenicity, focusing on virulence factors, immune evasion strategies, and phenotypic plasticity. Additionally, we explore emerging anti-virulence strategies as potential therapeutic interventions. By consolidating these insights, this review aims to guide future research and inform the development of new approaches to address this escalating public health challenge.
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.
The human microbiome, comprising trillions of microorganisms across multiple body sites, is increasingly recognized as a key contributor to host immunity, metabolism, and neurobiology, influencing development and disease susceptibility throughout life. Rather than acting in isolation, microbial communities operate within a complex host-environment system shaped by genetics, diet, lifestyle, and medical exposures. Conceptually, the microbiome can be understood as part of a host-microbe meta-organism and, from a translational perspective, as a dynamic and potentially modifiable organ system. While short-term perturbations such as antibiotics may transiently disrupt microbial ecosystems, persistent maladaptive configurations, commonly termed dysbiosis, are associated with metabolic disease, chronic inflammation, neurodevelopmental disorders, and cancer, although causality remains context dependent. This review synthesizes the functional roles of beneficial microbes and their metabolites, the mechanistic and clinical implications of dysbiosis, and immune pathways shaped by microbial signals. We further discuss emerging therapeutic strategies, including dietary modulation, probiotics, engineered microbial consortia, postbiotics, and fecal microbiota transplantation, enabled by multi-omics technologies, organoid models, and computational frameworks. Key challenges include defining context-specific microbial health, ensuring durable engraftment, and addressing regulatory and ethical considerations. Framing the microbiome as a dynamic component of host physiology provides a foundation for microbiome-guided precision and preventive medicine.
Physiological hemostasis is a balance between pro- and anticoagulant pathways, with multiple factors, regulators, and cellular components. Hemostasis is also closely associated with inflammation and immune response. In leptospirosis, a zoonotic disease caused by pathogenic spirochetal bacteria of the genus Leptospira, the hemostatic equilibrium is disturbed, resulting in coagulopathies that ultimately result in hemorrhages. Thrombocytopenia is a common complication in the affected patients and is often associated with poor clinical outcomes and high mortality. To date, the reports unraveling the origin of the molecular pathogenesis of leptospirosis hemostatic disturbances are scarce. In this review article, we summarize and analyze the complex pathophysiology of hemostatic impairment in the illness with a focus on the role of endotheliopathy, induction of pro-coagulant and pro-inflammatory states, and platelet dysfunction. We believe this can guide future studies aiming to unravel the molecular mechanisms underlying coagulopathy in leptospirosis to improve our understanding based on evidence, which will give insight into novel interventions to tackle the disease.
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.
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.
The incidence and prevalence of nontuberculous mycobacterial (NTM) lung disease (LD) cases are rising, with diagnosis and treatment proving difficult. With the preponderance of viable NTM in both natural and engineered environments, the understood route of human infection is through environmental exposures. In an effort to decrease the occurrence of NTM LD, methods to reduce environmental NTM exposures are of great interest to people with infection and the clinical community. In 2013, coauthor Falkinham summarized methods known at the time to reduce exposure to LD-causing Mycobacterium avium. The objective of this current review was to perform an updated PubMed, Web of Science, and Google Scholar literature search spanning 2014-2025 for newly reported methods and newer studies that expand on known mitigation strategies. In total, 31 articles were found. Among these new reports that posed new or improved methods to reduce environmental NTM exposure, risk assessment remains limited underscoring the need for more research in this area. We propose a feasible solution may be to revisit the "healthy home" concept and to consider the engineered environmental microbiome interactions when designing future homes.
