The Microbe最新文献

{"title":"Advancements in non – conventional therapeutics: A multi-targeted approach to Klebsiella pneumoniae biofilm management","authors":"Vanjinathan Mani,&nbsp;Nikita Gupta,&nbsp;Ethakoti Reddikavitha,&nbsp;Veronika Shalini,&nbsp;Mariselvam Thangavel,&nbsp;Sathiavelu Arunachalam","doi":"10.1016/j.microb.2026.100781","DOIUrl":"10.1016/j.microb.2026.100781","url":null,"abstract":"<div><div><em>Klebsiella pneumoniae</em>, one of the major multidrug-resistant opportunistic pathogens, poses a severe challenge in the field of healthcare, causing persistent, treatment-refractory infections owing to its intense biofilm-forming capacity. This review discusses non-conventional antibiofilm strategies, such as bacteriophage, plant phytochemical, and algal metabolite-based approaches, to treat <em>Klebsiella pneumoniae</em> infections as an alternative to traditional antibiotic therapy. Bacteriophage therapy facilitates targeted lysis of biofilm-embedded cells, while phytochemicals and algal metabolites interfere with the adhesion pathways and quorum sensing of <em>K. pneumoniae</em>, offering a multi-targeted, synergistic approach to effectively treat biofilms produced by <em>K. pneumoniae</em>. Nonetheless, critical translational barriers remain, including the emergence of phage-resistant mutants, suboptimal pharmacokinetic profiles, and a lack of standardized <em>in vivo</em> and clinical validation</div></div>","PeriodicalId":101246,"journal":{"name":"The Microbe","volume":"12 ","pages":"Article 100781"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148934315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scalable isolation of soil genomic DNA from microbial eukaryotes to multicellular micro‑ and mesofauna","authors":"Sannakajsa Velmala,&nbsp;Tero Tuomivirta,&nbsp;Juha-Matti Pitkänen,&nbsp;Satu Latvala,&nbsp;Taina Pennanen","doi":"10.1016/j.microb.2026.100786","DOIUrl":"10.1016/j.microb.2026.100786","url":null,"abstract":"<div><div>Global initiatives emphasise the need for harmonised soil biodiversity assessments. Efficient DNA extraction methods that accommodate larger soil volumes are essential for capturing organisms at higher trophic levels than bacteria and fungi and for supporting extensive sampling campaigns. We developed and evaluated a scalable, cost-efficient, and automation-ready soil DNA isolation protocol and compared its performance with two widely used commercial extraction methods: Qiagen DNeasy PowerSoil Pro (0.25 g soil input) and Qiagen DNeasy PowerMax Soil (2.5 g soil input). Four contrasting soil types representing agricultural and forest ecosystems (mull, sandy till, peat, and coarse mineral soil) were analysed. The new protocol combines bead-beating in sodium thiocyanate lysis buffer with either silica-membrane or carboxyl-coated magnetic bead purification and was tested using soil inputs of 2.5 g and 5 g for one soil type. DNA extracts were sequenced on an Illumina MiSeq platform using universal eukaryotic 18S rRNA gene primers to characterise soil metazoans and microbial eukaryotes. The developed protocol, combining a tenfold increase in soil input with commercial kit purification, produced the highest DNA yields in three of four soil types, increasing DNA recovery by up to 2.3-fold compared with the commercial maxiprep method. It also consistently detected the greatest metazoan richness, recovering up to 103% more taxa than the conventional miniprep method and up to 82% more taxa than the commercial maxiprep method. The carboxyl-coated magnetic bead workflow also performed well, recovering up to 83% more metazoan taxa than the miniprep method and up to 55% more taxa than the maxiprep method, particularly in forest soils. For microbial eukaryotes and protists, the commercial maxiprep and combination of developed high lysis volume and commercial kit silica purification protocols generally yielded the highest richness in agricultural soils, whereas the developed protocol performed best in coarse xeric forest soils. These results indicate that at least a tenfold increase in soil input relative to conventional 0.25 g extractions is required for reliable characterisation of mesofauna diversity, while further increases may provide additional gains. The developed DNA isolation protocol offers a solution for large-scale soil biodiversity assessments, supporting the integration of higher trophic levels into eDNA-based monitoring frameworks and future soil health monitoring programmes.</div></div>","PeriodicalId":101246,"journal":{"name":"The Microbe","volume":"12 ","pages":"Article 100786"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148934468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative assessment of strategic application of mono-and-cocktail phage therapy in combatting dual-species biofilm architecture: A new hope for medical device sanitization","authors":"Bershiyal Sugumar,&nbsp;Ramya Juliet,&nbsp;Rithviha Thirumurugan,&nbsp;Oishi Mitra,&nbsp;Nissy A. Bovas,&nbsp;Yogeswaran Jagadeesan,&nbsp;Prasanth Manohar,&nbsp;Ramesh Nachimuthu","doi":"10.1016/j.microb.2026.100783","DOIUrl":"10.1016/j.microb.2026.100783","url":null,"abstract":"<div><div>Invasive and implant-associated biofilms represent a hypercritical challenge in clinical settings where polymicrobial pathogens, including both Gram-positive and Gram-negative bacteria, colonise on medical devices, such as catheters, endotracheal tubes and pacemakers. These recurrences pose a serious threat as it leads to treatment failure, persistent infections and prolonged hospitalization, as these biofilms and their causative agents are highly resistant to existing therapies. This study investigates the therapeutic potential of mono-and-cocktail bacteriophages against dual-species biofilms (<em>Klebsiella pneumoniae - Escherichia coli</em> and <em>Pseudomonas aeruginosa - Acinetobacter baumannii),</em> mimicking hospital-acquired biofilms associated with catheters (catheter-associated urinary tract infections) and endotracheal tubes (ventilator- associated pneumonia). The efficacy of phage therapy in various stages of biofilm development was assessed from planktonic cell proliferation, biofilm formation, and preformed biofilm eradication with an average of 1.58, 2.53, and 1.7-fold reductions in mono-phage treatments, respectively, while phage cocktails demonstrated a significant reduction of 3.22, 4.5, and 2.41-fold on average respectively. Comparative analysis indicates that phage cocktails were more effective than mono-phage treatments in the reduction of biofilm development in medical devices, with scanning electron microscopy (SEM) showing a substantial decrease in bacterial biomass and morphological shrinkage of cells on the medical devices. Our study emphasises the importance of phage cocktails as a therapeutic strategy to combat polymicrobial biofilms associated with device-associated infections.</div></div>","PeriodicalId":101246,"journal":{"name":"The Microbe","volume":"12 ","pages":"Article 100783"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148934469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioprospecting and functional characterization of crude extracellular lipases from Antarctic Serratia sp. with production optimization by RSM","authors":"Jeffrey Vargas-Pérez,&nbsp;Nicole López-Ponce,&nbsp;Maria I. Arias-Pizarro,&nbsp;Michael Chóez-Dominguez,&nbsp;Aracely Paguay-Salcan,&nbsp;Liliana Villao,&nbsp;Efrén Santos-Ordóñez,&nbsp;Nardy Diez","doi":"10.1016/j.microb.2026.100787","DOIUrl":"10.1016/j.microb.2026.100787","url":null,"abstract":"<div><div>Antarctic ecosystems host diverse psychrophilic microorganisms, and soils influenced by seabird colonies, which are enriched in organic matter, represent promising sources of cold-adapted microorganisms with biotechnological potential. In this study, lipase-producing bacteria were bioprospected from Antarctic soils using selective enrichment and functional screening. From 166 isolates, 61 were selected for primary lipolytic screening of which 11 showed lipolytic activity. Two representative isolates were subsequently selected for molecular identification and optimization studies. Partial 16S rRNA gene analysis assigned both isolates to the genus <em>Serratia</em>. Crude extracellular lipase production was optimized using Response Surface Methodology (RSM), with substrate concentration, pH, and temperature as independent variables. For isolates ANT_10, optimization increased volumetric lipase production by 44.1%, resulting in volumetric activity of 7.78 U·mL⁻¹ under the predicted optimal conditions. The crude extracellular enzyme preparations exhibited broad pH stability (pH 2–10) and retained measurable residual activity after incubation at temperatures ranging from −80–50 °C. Both isolates showed maximum residual activity at neutral pH (7–8) and marked cryotolerance, maintaining up to 61% residual activity following exposure to subzero temperatures. Compared with a commercial microbial consortium, the Antarctic crude enzyme preparation exhibited greater residual stability following low-temperature incubation. Although this study evaluated crude extracellular enzyme preparations, which may contain interfering extracellular components and exhibit batch-to-batch variability, the results provide a foundation for future purification, biochemical characterization, and evaluation of these cold-active biocatalysts under application-relevant conditions. These findings highlight the potential of Antarctic <em>Serratia spp</em>. as a source of cold-active extracellular lipases for low-temperature biotechnological applications.</div></div>","PeriodicalId":101246,"journal":{"name":"The Microbe","volume":"12 ","pages":"Article 100787"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148934313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an alternative method for neutralization test of Japanese encephalitis virus using pig sera in national epidemiological surveillance program in Japan","authors":"Shunsuke Yazawa,&nbsp;Kotoha Yoshida,&nbsp;Yumiko Saga,&nbsp;Takahisa Shimada,&nbsp;Mayumi Nagoya,&nbsp;Nao Kobashi,&nbsp;Mami Matsuda,&nbsp;Ryosuke Suzuki,&nbsp;Shigeru Tajima,&nbsp;Chang-Kweng Lim,&nbsp;Hideki Tani","doi":"10.1016/j.microb.2026.100788","DOIUrl":"10.1016/j.microb.2026.100788","url":null,"abstract":"<div><div>We previously reported that the cytopathic effect (CPE) and single-round infectious particles (SRIPs) assays are useful alternatives to the focus-forming assay method for testing human Japanese encephalitis virus (JEV) susceptibility. In this study, we investigated whether these alternative methods were useful for testing JEV antibodies in pig sera in the same survey. A total of 240 serum samples from 6-month-old pigs were used in this study. Antibody titers were evaluated using four methods: the hemagglutination inhibition (HI) assay, currently used for pig serum in the national epidemiological surveillance program for vaccine-preventable diseases in Japan; the focus-forming assay, which is currently used for human serum; and the CPE and SRIPs assays, both previously evaluated using human serum. Unfortunately, the antibody titers in the HI assay showed almost no correlation with those of other methods. However, if the presence or absence of antibodies is determined instead of titer, using each assay method, a concordance rate &gt; 90% was observed for all combinations of assay methods. Among the evaluated assays, the SRIPs assay showed excellent agreement with conventional neutralization assays and may serve as a practical alternative for evaluating JEV neutralizing antibodies in pigs.</div></div>","PeriodicalId":101246,"journal":{"name":"The Microbe","volume":"12 ","pages":"Article 100788"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148934479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental Pseudomonas aeruginosa in groundwater: Association between multidrug resistance, biofilm formation and surface physicochemical properties","authors":"Abdelwahid Assaidi ,&nbsp;Mohamed Amzil ,&nbsp;Mourad Elgoulli ,&nbsp;Chorouk Zanane ,&nbsp;Kaoutar ELFazazi ,&nbsp;Mostafa Ellouali ,&nbsp;Hassan Latrache ,&nbsp;Hafida Zahir ,&nbsp;Mustapha Mebrouki ,&nbsp;El Mostafa Mliji","doi":"10.1016/j.microb.2026.100750","DOIUrl":"10.1016/j.microb.2026.100750","url":null,"abstract":"<div><div><em>Pseudomonas aeruginosa</em> is a Gram-negative pathogen widely isolated from various environments, including soil, water, and clinical settings. The capacity to persist, form biofilm and resist to antibiotics makes this bacterium a significant public health concern. The aim of this study was to determine the prevalence of <em>P. aeruginosa</em> isolated from well groundwater samples collected from diverse sites, and to evaluate the antimicrobial susceptibility profiles, Biofilm formation capacity, and the surface physicochemical properties of the isolates. A total of 80 samples were analyzed and the antibiotic susceptibility was determined using EUCAST standardized disk diffusion method. Biofilm formation and surface physicochemical characterization were evaluated. Our study revealed a 17.5% (14/80) prevalence of <em>P. aeruginosa</em> in well water samples, with resistance to some commonly used antibiotics; 35.7% of the isolates were classified as Multidrug-resistant (MDR). The studied strains showed a strong capability to form biofilms exceeding 7 Log CFU/cm² on galvanized steel. A significant correlation was observed between biofilm formation, surface physicochemical properties, and MDR. This study highlights the importance of monitoring groundwater quality and application of effective strategies to reduce health risks associated with <em>P. aeruginosa</em> contamination.</div></div>","PeriodicalId":101246,"journal":{"name":"The Microbe","volume":"11 ","pages":"Article 100750"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148231251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kingdom level microbial interaction network analysis for deciphering the potential pathobiome of oil palm leaf blight","authors":"Abiodun Abeeb Azeez ,&nbsp;Daniel Ofeoritse Esiegbuya ,&nbsp;Adebola Azeez Lateef ,&nbsp;Fred O. Asiegbu","doi":"10.1016/j.microb.2026.100743","DOIUrl":"10.1016/j.microb.2026.100743","url":null,"abstract":"<div><div>Oil palm leaf blight is an economically significant disease but remain understudied. In this study, we hypothesized that kingdom-level microbial interactions drive the transition from asymptomatic to symptomatic states and reshape microbial ecological roles, thereby contributing to disease development. To test this, we integrated 16S rRNA gene and ITS amplicon sequencing with correlation-based network inference to examine intra- and interkingdom interactions among bacterial and fungal communities in leaf, root and soil samples. Although alpha and beta diversity analyses showed no significant differences in microbial composition between health states, network analysis revealed pronounced shifts in microbial interaction patterns. This indicates that differences in taxa connectivity, rather than taxa presence or abundance, distinguish asymptomatic from symptomatic communities. Symptomatic microbiomes exhibited more connected and restructured networks, suggesting functional reorganization. Notably, <em>Ceramothyrium fici</em>, one of the most abundant fungal keystone taxa in symptomatic communities, formed cross-kingdom interaction networks with bacterial genera, including <em>Caulobacter</em> and <em>Streptomyces</em>, along with other fungi, including <em>Acremonium hennebertii</em>, creating modules that may facilitate disease progression. Network topology further revealed increased connectivity, altered modularity and the emergence of keystone taxa. Overall, these findings suggest that oil palm leaf blight may be associated with shifts in microbial interaction networks, particularly bacterial–fungal relationships and highlight the potential value of network-based approaches for understanding disease-related microbiomes.</div></div>","PeriodicalId":101246,"journal":{"name":"The Microbe","volume":"11 ","pages":"Article 100743"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of menthone and menthol extracts from peppermint (Mentha piperita L.) on mecC-harboring methicillin-resistant Staphylococcus aureus","authors":"Alina Rafique ,&nbsp;Khadija Gilani ,&nbsp;Syed Sohail Ahmad ,&nbsp;Muhammad Ammar ,&nbsp;Aqel Albutti","doi":"10.1016/j.microb.2026.100749","DOIUrl":"10.1016/j.microb.2026.100749","url":null,"abstract":"<div><div>The increasing antibiotics resistance of Methicillin-Resistant <em>Staphylococcus aureus</em> (MRSA) is a global concern, necessitating alternative treatment options. This study was aimed to address this issue by investigating the potential antibacterial activity of menthol and menthone, derived from <em>Mentha piperita L.</em> essential oil, against community acquired (CA) MRSA strains carrying the <em>mecC</em> gene, which is associated with methicillin resistance. Gas Chromatography was applied to MRSA isolates to identify the composition of the peppermint oil, which revealed the presence of various compounds consistent with previous studies. PCR was performed by designing specific primers to detect the <em>mecC</em> gene, and qPCR was conducted to validate the presence of the <em>mecC</em> gene in the MRSA isolates. MIC and MBC assays were employed to assess the antibacterial activity of menthol and menthone against the CA-MRSA strains. Results indicated that menthol exhibited higher efficacy compared to menthone, particularly against <em>mecC</em>-positive strains. Statistical analysis utilizing ANOVA and the Tukey-Kramer's multiple comparison test supported the significance of menthol as an effective agent against CA-MRSA strains. These findings underscore the promising potential of menthol derived from <em>Mentha piperita L.</em> essential oil in combating CA-MRSA infections, particularly in strains carrying the <em>mecC</em> gene. These insights also provide a steppingstone towards the development of novel treatment strategies to combat the escalating challenge of antibiotic resistance and ensuring effective healthcare management.</div></div>","PeriodicalId":101246,"journal":{"name":"The Microbe","volume":"11 ","pages":"Article 100749"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148231094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combinatorial application of gentamicin and tobramycin causes enhanced antimicrobial action against Methicillin Resistant Staphylococcus aureus: A study with artificial neural network","authors":"Ritwik Roy ,&nbsp;Ayan Chatterjee ,&nbsp;Saranya Trivedi ,&nbsp;Poulomi Chakraborty ,&nbsp;Alakesh Maity ,&nbsp;Debolina Ganguly ,&nbsp;Saranya Udayakumar ,&nbsp;Gopalarethinam Janani ,&nbsp;Mahashweta Mitra Ghosh ,&nbsp;Koyeli Girigoswami ,&nbsp;Sarita Sarkar ,&nbsp;Sharmistha Das ,&nbsp;Payel Paul ,&nbsp;Ranojit Kumar Sarker ,&nbsp;Moumita Malik ,&nbsp;Prosun Tribedi","doi":"10.1016/j.microb.2026.100742","DOIUrl":"10.1016/j.microb.2026.100742","url":null,"abstract":"<div><div>Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) poses a formidable challenge to public healthcare primarily due to its resistance to β-lactam antibiotics. This resistance is mediated by the expression of an altered penicillin-binding protein (PBP2a). Consequently, the global prevalence of MRSA has increased morbidity and healthcare costs, emphasizing the urgent need for innovative antimicrobial strategies. This study specifically investigates the potential of a combinatorial approach using gentamicin and tobramycin to effectively target the MRSA-borne infections. <em>In silico</em> assessment of pharmacokinetic profiles and biological parameters indicated that both gentamicin and tobramycin possess favourable drug-like properties. Additionally, the molecular docking analysis suggested that these aminoglycosides target distinct, non-overlapping regions within the 30S ribosomal subunit. Furthermore, <em>in vitro</em> studies revealed that co-administration of gentamicin and tobramycin significantly enhanced the inhibition of MRSA growth compared with monotherapy. Fractional Inhibitory Concentration Index (FICI) confirmed a strong additive interaction (FICI=0.63). To optimize the therapeutic efficacy, an artificial neural network (ANN) model trained on 118 distinct <em>in vitro</em> data points to predict optimal combinatorial concentrations. The ANN optimized combinatorial dosages exhibited robust antibacterial efficacy against MRSA. Finally, validation using an MRSA-infected zebrafish embryo model confirmed that the ANN-optimized combinations effectively combat controlled MRSA infections without observable toxicity. These findings suggest that leveraging ANNs to determine optimal combinatorial dosages of gentamicin and tobramycin could be a promising strategy for managing MRSA-mediated infections.</div></div>","PeriodicalId":101246,"journal":{"name":"The Microbe","volume":"11 ","pages":"Article 100742"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding biofilm tolerance in clinical infections: Matrixome architecture, metabolic zonation, and therapeutic implications","authors":"Thandeeswaran Murugesan ,&nbsp;Sugandhi Pugazhendhi ,&nbsp;Malarmathi Muthukumar ,&nbsp;Karthika Arumugam ,&nbsp;Rakesh Sehgal","doi":"10.1016/j.microb.2026.100753","DOIUrl":"10.1016/j.microb.2026.100753","url":null,"abstract":"<div><div>Biofilm-associated infections continue to pose a major challenge in clinical and public health due to their high tolerance to antimicrobial agents and host immune defences. Accounting for up to 80% of chronic human infections, unlike genetic resistance, biofilm tolerance is a reversible, phenotypic condition caused by the organised matrixome. Biofilm tolerance arises from structural protection conferred by the extracellular matrix and metabolic heterogeneity within the community. This review covers the structural and physiological factors of tolerance, emphasising metabolic zonation, stress-induced dormancy (persister cells), and transport-based protection through increased efflux systems. We explore emerging ideas such as tolerance memory, host-driven selective pressures, and the pharmacokinetic (PK) mismatch caused by spatial drug gradients within the biofilm structure. Despite advances in understanding mechanisms, a significant gap remains in translation due to the reliance on planktonic-based diagnostics and standard susceptibility measures (e.g., MIC) that do not reflect biofilm recalcitrance. We suggest shifting toward \"biofilm-aware\" clinical approaches that incorporate spatial transcriptomics, AI-driven predictive models, and matrix-disrupting adjunct therapies, including nanotechnology, phage therapy, and AI–guided interventions. To promote global equity in managing these infections, interdisciplinary collaboration and accessible diagnostics are essential. Eradicating pathogens through a tolerance-informed control strategy is crucial for sustainably managing chronic and recurrent infections.</div></div>","PeriodicalId":101246,"journal":{"name":"The Microbe","volume":"11 ","pages":"Article 100753"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148231097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}