Efflux-mediated resistance is a critical mechanism by which bacterial pathogens evade antibiotic treatment, posing significant challenges to effective infection management. As the first line of defence mechanism in bacteria, efflux pumps actively expel antibiotics, contributing to multidrug resistance. Recent advances in nanotechnology offer promising solutions, with nanobiotics emerging as a novel approach to combating efflux-mediated resistance. Nanobiotics are engineered nanoscale materials with antibacterial properties. They can be designed to inhibit efflux pump function, enhance drug accumulation, and disrupt bacterial cell membranes, thereby overcoming traditional resistance mechanisms. Nanobiotics can easily fuze with the bacterial cell wall and facilitate the release of antibiotics into the cytoplasm. This review provides an overview of efflux-mediated resistance mechanisms, highlights recent nanotechnology developments to design and formulate nanobiotics, and examines their potential to inhibit efflux pumps in multidrug-resistant bacterial strains. By targeting efflux systems, nanobiotics offer a potent and innovative approach to restoring the efficacy of conventional antibiotics and advancing the treatment of multidrug-resistant bacterial infections.

Novel antibacterial agents are critically needed in light of the constant menace posed by bacterial infections and subsequent emergence of antibiotic-resistant strains. Quality of life has been improved remarkably through antibiotics that have fought microbial pathogens. . Luteolin has shown effectiveness against both gram-positive and gram negative bacteria. Luteolin and its derivatives, as novel phytochemical antimicrobial agents, exhibit activity against both Gram-positive and Gram-negative bacteria . Luteolin target bacteria by disrupting their cell membranes, inhibiting nucleic acid synthesis, and interfering with key enzymes. It also blocks quorum sensing and biofilm formation, crucial for bacterial virulence and resistance. Luteolin, despite its therapeutic potential, has limited clinical use due to poor water solubility and low bioavailability, leading to reduced absorption and rapid metabolism in the body. To address these issues, researchers are exploring advanced formulations like nanoparticles and liposomes to improve its solubility and effectiveness. Recent formulation advancements aim to enhance luteolin's delivery and efficacy as an antibacterial agent. However, in-depth studies are essential to unlock its full therapeutic potential for clinical use. This review highlights luteolin's antibacterial capabilities, usage challenges, and recent progress, stressing the importance of further research to fully leverage its benefits.

is globally recognized for its role in chronic gastritis, peptic ulcer disease, and gastric cancer. Yet despite decades of research and standardized eradication protocols, treatment failures and disease recurrence remain frustratingly common. While antibiotic resistance has been a central focus, emerging data suggest that employ additional, underappreciated survival strategies that extend its pathogenic potential beyond the stomach. This review redefines as a versatile pathogen capable of persisting through underappreciated survival strategies: the coccoid viable but non-culturable (VBNC) state, intracellular survival within yeast cells, and the release of outer membrane vesicles (OMVs). Each of these forms confers unique advantages: coccoid cells withstand environmental stress and evade standard diagnostics; yeast-harbored may resist antibiotics, enable vertical transmission, and serve as long-term reservoirs; and OMVs can traffic toxins like VacA and CagA to distant tissues, triggering inflammation, apoptosis, and barrier dysfunction without bacterial contact. This review proposes that these alternative forms are not incidental anomalies, but integral to 's persistence, dissemination, and disease spectrum, including potential extra-gastric effects. Recognizing and targeting these hidden states may hold the key to improved diagnostics, more durable eradication, and a deeper understanding of one of medicine's most enduring pathogens.

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.

is a caries-associated bacterium with the ability to adhere to the surface of oral tissues and promote biofilm formation. For this purpose, expresses a range of specialized surface adhesins, among which collagen-binding proteins (CBPs) have demonstrated an important function regarding attachment to dentin, bacterial coaggregation, and extracellular matrix invasion. Understanding the mechanobiological behavior of CBPs, particularly their interaction with collagens during the process of bacterial adhesion, is crucial for developing novel strategies to prevent biofilm formation in oral and remote tissues. Therefore, this review summarizes recent evidence regarding the main mechanical properties of the relevant CBPs SpaP, WapA, Cnm, and Cbm, and how their mechanobiological and adhesive characteristics play an important role in their virulence toward the host. Particularly, we will focus on how state-of-the-art interdisciplinary approaches such as atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and single-cell force spectroscopy (SCFS) have been employed to characterize and CBP attachment to collagen substrates and mechanical behavior in real-time and under physiological conditions. Altogether, the potential use of AFM SMFS and SCFS to explore novel anti-biofilm molecules against remains an exciting possibility for the development of caries-preventive treatments in the future.

Many consider the gut microbiota an organ of the human body; although the view is controversial, its effect on overall human health cannot be denied. The mucosal gut bacteria are physiologically distinct from those inhabiting the gut lumen or fecal material. They have a central role in regulating the intestinal mucosal barrier properties, protecting against intestinal inflammation. The human gut-associated bifidobacteria can form robust biofilms that can form distinct microcolonies with colonization patterns unique to a species or across several species. The species-specific spatial distribution hints at an undeciphered fitness advantage in the host gut milieu. The antipathogenicity of indigenous strains represents a promising therapeutic strategy against pathogenic biofilms that resists existing medical therapies. Harnessing their biofilm phenotype constitutes a central premise of the fourth-generation probiotics, which can better benefit the human gut. The beneficial bacteria could be harnessed to fight infectious diseases in developing countries such as Pakistan, plagued by food insecurity. This evidence suggests that further studies are needed to test the potential of these probiotic candidates as live-biotherapeutic agents.

The 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.

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.

Chronic wound infections, particularly those associated with (), 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 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 , , and spp., which interfere with 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.

The genus contains over 180 species, and new species are added frequently. Among these are several obligate pathogens, namely and the species of the complex; however, the vast majority are environmental bacteria that occupy numerous habitats and are collectively referred to as nontuberculous mycobacteria (NTM). Most NTM are harmless to humans, but the ability of some species to cause infections in people has been increasingly recognized over the past several decades. subs. has emerged as one of the most common opportunistic pathogens, usually causing pulmonary infections in susceptible people following environmental exposure. 's ability to form biofilms is key to its survival in environments that place it in close proximity to susceptible populations. Their capacity to form biofilms may also be an important aspect of their pathogenesis and known antibiotic resistance. In this review, we discuss the pathogenesis of this important mycobacterial species, what we know of its ability to form biofilms and and gaps in our knowledge of these processes. We also discuss how we may leverage our understanding of molecules involved in biofilm formation and biofilm matrix composition to develop new therapeutics targeting biofilm formation.

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.

Human fungal infections are increasingly being recognized as a significant global health threat. The burden of fungal diseases is escalating, primarily due to the rising number of at-risk individuals, compounded by the limited availability of antifungal therapies that are both effective and minimally toxic. Phages, viruses that specifically infect and kill bacteria, have long been investigated for their therapeutic potential. However, despite their success in bacteriology, the applications of phages in antifungal therapy are under active research. Particularly, phages could be used to treat fungal infections by engineering them to express fungal antigens on their surfaces, and this would trigger specific immune responses, such as activating Th1 and Th17 responses or inducing the production of neutralizing antibodies. Phages could also be combined with photodynamic inactivation (PDI) or antimicrobials to enhance treatment efficiency. Meanwhile, phages can exert direct antifungal effects by depleting iron, a crucial nutrient for fungal growth. This paper provides a comprehensive review of the phage-based antifungal treatment.

( 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 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 infection. These include the development of urease inhibitors, anti-adhesion therapies, treatments for intracellular 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.

Foodborne illness is a critical food safety and public health concern, often resulting from contamination events by resident pathogens in food processing environments (FPEs). , the causative agent of listeriosis, can persist in FPEs over long time periods. Despite rigorous research on the phenotypic and genotypic traits of , 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 to persist in food processing environments.

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 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.

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) genes" were first described on plasmids isolated from clinically relevant . 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 genes. We then performed an analysis of 184,000 high-quality, prokaryotic (meta)genomes, which revealed that and 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".

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.

The genus 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.

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 , , , , , , and , 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.

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.

Biofilm formation is a complex process in which bacteria adhere to surfaces and create a protective matrix. Biofilms shield bacteria, such as , from antibiotics and the host immune system, greatly facilitating their pathogenesis by enabling immune evasion and antimicrobial resistance. This review examines the stages of 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 infections.