Critical Reviews in Microbiology最新文献

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 genus Enterococcus has been extensively investigated, emphasizing either its potential as a probiotic in fermented foods or its opportunistic pathogenic nature, particularly in hospital settings. This review focuses on the defining characteristics of enterococci species to better understand their dual nature, with the goal of establishing a universal method to safely and effectively characterize probiotic enterococci. Despite harboring genes for potentially harmful enzymes and metabolites, enterococci have traditionally been used to improve the flavor profiles of artisanal dairy products. Additionally, certain strains produce antimicrobial compounds, particularly bacteriocins, which help control the microbial composition of food products. These bacteriocins have been extensively explored as alternatives to antibiotics, driven by the rapid increase in antimicrobial resistance across several bacterial species. However, enterococcal isolates of nosocomial origin are harmful. Recent studies have clarified the divergent lineages that resulted in the emergence of pathogenic and nosocomial strains, thus improving the selection process for determining whether an isolate can be utilized as a probiotic. The insights gathered in this review have important implications for developing regulations on and optimizing the use of enterococci.

The metalloid tellurium (Te) is toxic to bacteria; however, the element is also extremely rare. Thus, most bacteria will never encounter Te in their environment. Nonetheless significant research has been performed on bacterial Te resistance because of the medical applications of the element. The so-called "tellurium resistance (Te^R) genes" were first described on plasmids isolated from clinically relevant Enterobacteriaceae. With time, it has become apparent that, given the rarity of Te on the planet, these genes may have functions beyond tellurium resistance. Nonetheless, the description of these genes as "tellurium resistance genes" has persisted. In this review, we first examine the history and discovery of the Te^R genes. We then performed an analysis of 184,000 high-quality, prokaryotic (meta)genomes, which revealed that terZABCDF, telA, and tehAB are relatively common in genome annotations and that they are frequently described as "tellurium resistance genes". We synthesized the literature to describe the functions of these ubiquitous genes beyond tellurium resistance. These genes have functions in diverse cellular processes including phage resistance, antibiotic resistance, virulence, oxidative stress resistance, cell cycle regulation, metal resistance, and metalation of exoenzymes. Considering this analysis, we propose that it is time to appreciate the multifunctional nature of the "tellurium resistance genes".

Fungal pathogens pose a global public health risk, driven by the alarming rise of antifungal resistance. The current antifungal pipeline remains limited to three main classes (azoles, polyene, and echinocandins). Additionally, fungal biofilms, with its extracellular matrix, further complicates the antifungal therapeutics. Despite the persistent challenges posed by biofilms in clinical medicine, advancements in research have led to the development of numerous antifungal approaches aimed at inhibiting the fungal growth, disrupting biofilm integrity and overcoming resistance mechanisms. This review explores the current understanding of antifungal resistance in human fungal pathogens, and emphasizes emerging therapeutics, including novel treatments, repurposed drugs, and natural products, with potential to outperform conventional therapies. Future experimental studies will further refine these recent therapeutic approaches, paving the way for innovative and more efficient biofilm eradication approaches.

Biofilms are microbial communities that adhere to surfaces and each other, encapsulated in a protective extracellular matrix. These structures enhance resistance to antimicrobials, contributing to 65-80% of human infections. The transition from free-living cells to structured biofilms involves a myriad of molecular and structural adaptations. Raman spectroscopy is an analytical technique that has recently been adapted for biofilm analysis. The ability to operate without interference from water makes Raman spectroscopy a valuable tool for in situ characterization of biofilms, including direct analysis from clinical samples. The technique also offers the advantage of imaging speed and the capacity to generate extensive chemical and molecular data from samples, whilst also being non-destructive. However, Raman spectroscopy is often limited by its low sensitivity, particularly when applied to microbial analysis. This limitation has been addressed with the advent of surface-enhanced Raman spectroscopy and stimulated Raman scattering microscopy. When used in combination with traditional methods, these Raman technologies can be incredibly useful for understanding the mechanisms underlying biofilm development, antimicrobial susceptibility testing, and detection and discrimination of microorganisms. In this critical review, the application of Raman spectroscopy and its derivatives as a tool for biofilm characterization is discussed along with its associated advantages and challenges.

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.

Endolichenic fungi (ELF) are symbiotic organisms residing in lichens. Since the initial report of its application in natural products and drug discovery, they have emerged as unique valuable sources of compounds with a wide range of structural diversity and biological activities. In this review, we critically examine current strategies to expand ELF metabolite diversity, with emphasis on the One Strain, Many Compounds (OSMAC) approach and metabolomics-guided profiling. We highlight how co-culture systems, epigenetic modifiers, and advanced data acquisition platforms can open new avenues for chemical space exploration. Genomic and transcriptomic studies, though still limited in ELF, reveal untapped biosynthetic potential and point toward integrative omics pipelines. Recent computational and artificial intelligence tools further accelerate genome-metabolome mining, structural elucidation, and prediction of bioactivity. We propose a forward-looking framework that combines OSMAC, integrative omics, and AI to maximize the natural product bioprospecting potential of ELF, while also uncovering their ecological roles within the lichen holobiome.

Foodborne illness is a critical food safety and public health concern, often resulting from contamination events by resident pathogens in food processing environments (FPEs). Listeria monocytogenes, the causative agent of listeriosis, can persist in FPEs over long time periods. Despite rigorous research on the phenotypic and genotypic traits of L. monocytogenes, no clear pattern has arisen to explain why some strains are able to persist. Researchers face definitional and methodological challenges, which influence identification and comparison of persistent and non-persistent strains. Moreover, only weak associations between persistence and gene-level patterns have been detected, necessitating new perspectives. In this review, we synthesize years of research based on whole genome sequencing, highlighting sequence-type and gene-level patterns linked to persistence. As these patterns do not robustly explain persistence, we critically assess how applied definitions and methodological approaches have shaped, and potentially biased, our current understanding. We evaluate existing hypotheses on persistence and suggest future research directions, integrating insights from ecology, evolution, and predictive modeling to disentangle factors and mechanisms that enable L. monocytogenes to persist in food processing environments.

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.

Chronic wound infections, particularly those associated with Staphylococcus aureus (S. aureus), present a significant clinical challenge due to biofilm formation and increasing antibiotic resistance. This review explores the emerging role of commensal bacteria and natural compounds in modulating S. aureus virulence, with a focus on the inhibition of the accessory gene regulator quorum-sensing system Agr. We highlight antimicrobial peptides secreted by skin commensals such as Staphylococcus epidermidis (S. epidermidis), Staphylococcus hominis (S. hominis), and Corynebacterium spp., which interfere with agr signaling, biofilm development, and toxin production. Additionally, we examine natural molecules derived from fungi and plants that target Agr and other regulatory systems (e.g. Staphylococcal accessory element Regulator Sensor/Regulator System, Autolysis-related Regulator Sensor/Regulator System and Staphylococcal accessory regulator A), offering promising antivirulence strategies. These findings underscore the therapeutic potential of microbiota-derived and natural antivirulence agents as adjuncts or alternatives to antibiotics. Further research is needed to evaluate their stability, safety, and clinical applicability.