Critical Reviews in Microbiology最新文献

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.

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.

Type IV pili are filamentous surface structures found in diverse bacterial species that provide specialized functions to bacteria, such as initiating cell aggregation via attachment to host cells. The structural filament is made up of polymers of pilin subunits. Gene expression of major pilins is typically the major factor deciding the timing of Type IV pilus filament assembly. Therefore, the regulation of pilin genes is often independent from other pilus biogenesis genes even when they are located within the same cluster. Such strictly regulated pilin transcription ensures that the pilus filament is expressed only when the bacterial cells require it, such as precise timing for a specialized function, or preventing potentially adverse situations like clearing by host defense systems or cell death by phage infection. This review will focus on the transcriptional regulation of Type IV major pilins found in bacteria, and speculate on the evolution of such regulatory systems by identifying similarities and differences across different bacterial phyla.

Carotenoids are isoprenoid pigments that are largely responsible for the red, pink, orange, and yellow pigmentation in bacteria. Despite their structural diversity, they share a similar general chemical structure. Carotenogenesis is a complex, multistep process, mediated by the crt gene products. The crt genes encode enzymes that catalyze a wide array of reactions within the carotenogenic pathways, sometimes showcasing broad substrate specificity. These enzymes are involved in processes such as condensation, desaturation, oxygenation, cyclization, hydroxylation, ketolation, glycosylation, acylation, elongation, and methylation of carotenoid intermediates. Some crt genes do not encode enzymes, but rather regulators of carotenogenesis. This review provides an in-depth exploration of the multitude of crt genes identified in various bacteria, emphasizing the pivotal role of Crt enzymes, their diverse functions within the different carotenogenic pathways and some of the reactions they catalyze. Additionally, the biosynthetic pathways of C30, C40, C45, and C50 carotenoids, as well as the production of certain rare carotenoids in bacteria, are explored. Overall, this review highlights the importance of crt gene products in the diverse and tightly regulated biosynthesis pathways of bacterial carotenoids.

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.

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.

Brevibacillus laterosporus is a ubiquitous bacterium that has been isolated from a wide range of abiotic and biotic habitats. Especially, it has been reported from various insects which supported the development of its mutualistic or pathogenic interaction with diverse insect species under co-evolutionary force. In the recent past, different B. laterosporus strains reported to produce multiple bioactive agents including antimicrobial peptides (AMPs) and antibiotics with diverse antimicrobial and antitumor activities. Further, whole genome sequencing of this bacterium revealed biosynthetic gene clusters which suggested its potential to produce multiple polyketides, non-ribosomal peptides, and bacteriocins. All these facts strongly suggest B. laterosporus as a potential bio-pesticidal or bio-control agent against a diverse species of insects and phytopathogens including bacteria and fungi which may lead to its application in the agricultural industry. Further, broad-spectrum antimicrobial action against drug-resistant and pathogenic bacteria along with antitumor activities suggested the potential for the development of bioactive molecules produced by B. laterosporus in the pharmaceutical and biotechnology industry including agriculture and food preservation. Overall, the present review is focused on the co-evolution of B. laterosporus with its diverse hosts that result in a diverse array of bioactive agents for various agricultural and therapeutic applications.

Biofilm formation is a complex process in which bacteria adhere to surfaces and create a protective matrix. Biofilms shield bacteria, such as Escherichia coli, from antibiotics and the host immune system, greatly facilitating their pathogenesis by enabling immune evasion and antimicrobial resistance. This review examines the stages of E. coli biofilm formation and their role in infections across various body sites, including the central nervous system, eyes, ears, teeth, respiratory tract, cardiovascular system, gastrointestinal tract, urinary tract, and medical device-related infections. Each infection site is thoroughly analyzed in terms of clinical manifestations, diagnostic challenges, treatment resistance, and implications for patient management. Furthermore, this review discusses therapeutic advancements, which are crucial for combating biofilm-associated infections. By unraveling the complexities of biofilms and developing novel therapeutics, researchers and clinicians can enhance strategies for diagnosing, treating, and preventing persistent E. coli infections.

Periodontal diseases, chronic inflammatory conditions initiated by dysbiotic microbial communities, are predominantly driven by the "red complex" pathogens. This review explores how glycosylation on surface molecules of Tannerella forsythia, Porphyromonas gingivalis, and Treponema denticola modulate their pathogenesis. Research reveal glycosylation profoundly impacts synthesis, stability and functionality of major virulence factors like gingipains, fimbriae and surface layer proteins in these keystone pathogens. Distinct glycan motifs facilitate immune evasion by masking antigenic epitopes, subverting immune recognition and skewing inflammatory responses. Remarkably, glycosylation signatures influence crucial virulence traits such as biofilm formation, host adhesion and invasion, potentiating persistence. Through evaluating current literature, this review unravels the interplay between glycosylation pathways and virulence expression, elucidating mechanisms underpinning glycan-mediated host-pathogen interactions and pathology progression. Emerging prospects of exploiting glycosylation as a diagnostic, therapeutic target and vaccine candidate are discussed. Synthesizing cutting-edge findings, this comprehensive review illuminates glycosylation's central role in periodontal pathogenesis.