Archives of Microbiology最新文献

{"title":"A review on fungal pathogens in the One Health framework: connecting plant, animal, and human health","authors":"Muhammad Ali,&nbsp;Saba Sana,&nbsp;Hafiz Husnain Nawaz,&nbsp;Saba Amjad,&nbsp;Qaiser Farid Khan","doi":"10.1007/s00203-026-05211-y","DOIUrl":"10.1007/s00203-026-05211-y","url":null,"abstract":"<div><p>The growing burden of fungal diseases on human, animal, plant, and environmental health is a serious global problem that requires a “One Health” approach beyond disciplinary silos. Fungal diseases are often neglected, yet their prevalence and importance are increasing at an alarming rate. Complex interactions among different host organisms, coupled with human activities, anthropogenic environmental impacts, climate change, globalization, and antifungal drug use, particularly in agriculture, are significant contributing factors. The emergence and spread of resistance to existing antifungal agents is one of the most important consequences, leading to poor treatment outcomes in both clinical and agricultural settings. Azole fungicides used in crops have been associated with the selection of resistant strains in some fungi common in the environment and associated with human disease, such as <i>Aspergillus flavus</i> and <i>Fusarium</i> spp., which have a unique enzyme paralogue <i>cyp51</i>C, and efflux pumps that flush out the azoles, thereby leading directly to treatment failure. The article explains how fungal pathogens can affect each of the three pillars of One Health. In plant health, fungal infections affect food security and economic outcomes, while the use of fungicides for treatment can lead to cross-resistance with clinical medications. In animal health, fungal diseases affect livestock well-being and productivity, and animals act as reservoirs for the zoonotic transmission of resistant strains to humans. In human health, the impact on immunocompromised populations is high, as invasive fungal infections result in significant morbidity and mortality. Limited availability of antifungal drugs, diagnostic challenges, and limited surveillance. To combat these multifaceted, interconnected challenges, a collaborative, multisectoral approach is imperative. Looking ahead, future initiatives should emphasize genomic and eco-epidemiological research to elucidate the drivers of emergence, anticipate outbreaks, and identify emerging threats. In conclusion, addressing the global burden of fungal diseases necessitates a holistic One Health approach that aligns surveillance, research, policy, and public health interventions to preserve the efficacy of existing treatments and protect the health of all interconnected domains.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"208 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization of PVL-positive methicillin-resistant Staphylococcus aureus (MRSA) isolates from skin and soft tissue infections in Alexandria, Egypt","authors":"Maged El-Ashker,&nbsp;Shahinda Rezk,&nbsp;Stefan Monecke,&nbsp;Mayada Gwida,&nbsp;Sherine Shawky,&nbsp;Elke Müller,&nbsp;Lisa Schönau,&nbsp;Lukas Rüttiger,&nbsp;Ralf Ehricht","doi":"10.1007/s00203-026-05169-x","DOIUrl":"10.1007/s00203-026-05169-x","url":null,"abstract":"<div><p>Data regarding the molecular epidemiology, clonal diversity, and resistance mechanisms of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) causing skin and soft tissue infections (SSTIs) in Egypt remain limited. This study aimed to characterize the clonal structure, resistance determinants, and virulence profiles of MRSA isolates from SSTIs in Alexandria, Egypt. We analyzed 38 non-duplicate MRSA isolates recovered between July and December 2024 from SSTI specimens submitted to a central microbiology laboratory serving hospitals and outpatient clinics in Alexandria, Egypt. Molecular characterization of antimicrobial resistance, virulence, and biofilm-associated genes were performed using DNA microarray analysis, assigning isolates to clonal complexes (CCs). The diagnostic performance of lateral flow assays (LFAs) for penicillin–binding protein 2a (PBP2a) and Panton–Valentine leukocidin (PVL) detection was evaluated against microarray results. Ten distinct CCs were identified, predominantly CC152 (28.9%) and CC1153 (23.7%). A high prevalence of PVL genes (<i>lukS-PV/lukF-PV</i>) was detected (78.9%), demonstrating significant lineage specificity (<i>p</i> &lt; 0.001) among CC152, and CC1153. Analysis of the antimicrobial resistance gene profiles revealed a broad genotypic resistance repertoire across the collection. Notably, 78.9% carried the fusidic acid resistance gene <i>fusC</i> and 71.1% carried the aminoglycoside resistance gene <i>aacA-aphD</i>, both significantly associated with CC152 and CC1153 (<i>p</i> &lt; 0.001). One isolate (2.6%; lineage CC1-MRSA-[V/VT + fus+ccrAB1]) was confirmed as vancomycin-resistant (VRSA). LFAs demonstrated 100% concordance with microarray results for both PBP2a and PVL detection. This study demonstrates a high prevalence of PVL-positive, multidrug-resistant MRSA lineages among SSTI isolates in Alexandria. The frequent detection of CC152 and CC1153 lineages co-carrying mobile genetic element (MGE)-borne resistance genes (<i>fusC</i> and <i>aacA-aphD</i>) highlights the expansion of multidrug resistance profiles among community-associated genetic backgrounds. Furthermore, the detection of a sporadic VRSA strain emphasizes the necessity of routine phenotypic susceptibility testing alongside molecular screening. The 100% concordance of LFAs supports their implementation as rapid, culture-based screening tools in laboratory diagnostic workflows to guide empirical antibiotic therapy and infection control.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"208 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148986618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a PapG–AcmA surface-associated antigen on Lactobacillus reuteri as a vaccine strategy against uropathogenic Escherichia coli","authors":"Meisam Akrami,&nbsp;Maryam Akrami,&nbsp;Amirhossein Amini,&nbsp;Parisa Haeri","doi":"10.1007/s00203-026-05214-9","DOIUrl":"10.1007/s00203-026-05214-9","url":null,"abstract":"<div><p>Urinary tract infections (UTIs) are highly prevalent across diverse populations, with uropathogenic <i>Escherichia coli</i> (UPEC) recognized as the leading cause, responsible for more than 85% of cystitis and acute pyelonephritis cases. Because bacterial attachment to the uroepithelium is the critical initial step in colonization and infection, blocking this adhesion represents one of the most effective preventive strategies. The PapG adhesin, located at the tip of P-fimbriae in P-type UPEC, is a key mediator of this attachment and therefore a promising vaccine target. In this study, a chimeric antigen was designed by fusing the 198-amino-acid receptor-binding domain of PapG (GenBank accession No. YP_543821.1) to the 85-amino-acid cell-wall anchoring domain of AcmA (accession No. NC_011751.1) via a pentameric EAAAK flexible linker, yielding a 314-amino-acid construct. The gene was subcloned into the pET21a expression vector and expressed in <i>E. coli</i> Origami (DE3) under 1 mM IPTG induction. The purified recombinant protein was verified by SDS-PAGE and Western blot analysis, and its surface association on <i>Lactobacillus reuteri</i> was confirmed by ELISA. Seventy BALB/c mice were allocated into five groups (14 mice per group) and received a triple-dose vaccination regimen at two-week intervals: alum-adjuvanted + PapG, PapG + formulated with Freund’s adjuvant, PapG-AcmA-associated <i>L. reuteri</i>, PBS-treated <i>L. reuteri</i>, and PBS alone as a negative control. Antigen-specific antibody responses and cytokine secretion profiles were subsequently evaluated. The findings indicate that adjuvanted PapG formulations elicit robust systemic Th1 and Th2 immune responses. Meanwhile, oral administration of <i>L. reuteri</i> surface-associated PapG-AcmA provides partial mucosal protection against UPEC colonization, likely driven by localized immunomodulation, and may serve as a promising mucosal vaccine platform.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"208 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of culturable endophytes and microbial communities in the rhizosphere and pitcher fluid of the carnivorous plant Nepenthes khasiana","authors":"Kiran Dhiman,&nbsp;Manisha Devi,&nbsp;Arun Kumar,&nbsp;Shiv Shanker Pandey,&nbsp;Jeremy Dkhar","doi":"10.1007/s00203-026-05190-0","DOIUrl":"10.1007/s00203-026-05190-0","url":null,"abstract":"<div><p>Endophytes colonize plant tissues through roots and shoots without causing harm and can move throughout the plant via its vascular system. However, little is known about culturable endophytes, particularly bacteria, in pitcher plants, and their possible entry through pitcher fluid remains unexplored. To address this gap, we isolated endophytes from the pitcher plant <i>Nepenthes khasiana</i>, and performed metagenomic analysis of its rhizospheric soil and pitcher fluid, from which bacteria and fungi were also isolated, to investigate the possible origin of these endophytes. We found that culturable endophytic bacteria were predominantly associated with roots and seeds, whereas endophytic fungi were more abundant across the <i>N. khasiana</i> pitcher. Although most endophytes were restricted to specific tissues, some exhibited a broader distribution across nearly the entire plant. Several OTUs from the rhizospheric soil matched endophytes at the genus level, including some that were also detected in the pitcher fluid. Specifically, three bacterial genera – <i>Enterobacter</i>, <i>Staphylococcus</i> and <i>Bacillus</i> – and one fungal genus, <i>Cladosporium</i>, detected in the pitcher fluid, matched the isolated endophytes. These findings suggest that endophytes in <i>N. khasiana</i> most likely originate from the rhizosphere, with possible migration into the pitcher fluid.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"208 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of oral microbiome diversity with prevalent cancer: a population-based cross-sectional study","authors":"Yanfei An,&nbsp;Chaoyu Pang,&nbsp;Zhirong Wu,&nbsp;Yafen Chu,&nbsp;Wenjuan Wan,&nbsp;Shanshan Gao,&nbsp;Ning Pu","doi":"10.1007/s00203-026-05188-8","DOIUrl":"10.1007/s00203-026-05188-8","url":null,"abstract":"<div><p>Oral microbiome interacts with other organ systems and significantly impacts human health. However, analysis of its role in cancer remains scarce. This study aims to explore the relationship between oral microbiome diversity and prevalent cancer. We analyzed 7727 adults from the 2009–2012 National Health and Nutrition Examination Survey. The linear and non-linear associations between α-diversity and cancer were evaluated using multivariable logistic regression analysis and restricted cubic spline functions. Principal coordinates analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) were also used to evaluate differences in β-diversity by cancer status. We found a negative association between oral microbiome α-diversity and the odds of cancer. After adjusting for all confounding covariates, participants in the highest tertile of diversity had 42–46% lower odds of cancer compared to those in the lowest tertile (OTU richness OR = 0.54, 95% CI 0.33–0.87, Ptrend = 0.007; Faith's phylogenetic diversity OR = 0.58, 95% CI 0.35–0.94, Ptrend = 0.012). Exploratory β-diversity analyses showed statistically significant but limited differences in overall microbial community composition according to cancer status. Subgroup analyses suggested a potential effect modification by age, with participants younger than 65 years showing sensitivity to modest elevation in microbiome diversity. Additionally, certain characteristics were associated with lower oral microbiome α-diversity, including age 40 onwards, female sex, lower income, and antibiotics use. Our findings reveal that higher oral microbiome diversity is associated with lower odds of having cancer, which suggests that microbiota profiles may have potential utility in cancer-related risk stratification.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"208 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The putative mitochondrial serine protease Pim1 regulates azole tolerance through redox homeostasis in Aspergillus fumigatus","authors":"Sha Wang,&nbsp;Ziqing Sun,&nbsp;Jingyao Cai,&nbsp;Yichan Cao,&nbsp;Libo Cao,&nbsp;Haoze Yu,&nbsp;Boying Xu,&nbsp;Guowei Zhong","doi":"10.1007/s00203-026-05204-x","DOIUrl":"10.1007/s00203-026-05204-x","url":null,"abstract":"<div><p><i>Aspergillus fumigatus</i> has been included in the World Health Organization’s (WHO) inaugural list of priority fungal pathogens for immunosuppressed individuals. Mitochondrial function is closely associated with antifungal susceptibility, and mutations in mitochondrial genes can modulate drug responses in Cyp51A-independent mutants. Using a previously constructed random insertional mutagenesis library, we identified <i>pim1</i>, a gene encoding a putative mitochondrial serine protease, whose mutation via T-DNA insertion regulates azole tolerance in the <i>A. fumigatus</i> Af293 strain. We found that deletion of <i>pim1</i> in the A1160 background was not essential for fungal viability but increased azole tolerance and attenuated virulence in <i>Galleria mellonella</i>. Pim1 was localized to mitochondria. Further mechanistic analysis revealed that the Δ<i>pim1</i> mutation did not affect intracellular ergosterol content or itraconazole (ITC) retention. Instead, it reduced intracellular reactive oxygen species (ROS) levels, and RNA-seq analysis revealed altered expression of genes involved in anaerobic respiration, ROS/aldehyde scavenging and proline metabolism, which may contribute to azole tolerance. Further experiments supported a role for oxidative homeostasis in this phenotype, as ROS scavenger vitamin C increased ITC tolerance in the WT strain but not in the mutant, whereas H₂O₂ diminished ITC tolerance in the Δ<i>pim1</i> mutant. Collectively, these findings provide new insight into non-Cyp51A-dependent mechanisms of azole tolerance.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"208 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent and niche-specific functional bacteriome of maize hybrid revealed by integrated metabarcoding and culturomics","authors":"Neelam Sheoran,&nbsp;Robin Gogoi,&nbsp;Govindasamy Venkadasamy,&nbsp;Vineeth Vijayan,&nbsp;Naveen Kumar,&nbsp;Shankar Lal Jat,&nbsp;Sujay Rakshit,&nbsp;Aundy Kumar","doi":"10.1007/s00203-026-05174-0","DOIUrl":"10.1007/s00203-026-05174-0","url":null,"abstract":"<div><p>The plant microbiome plays a pivotal role in plant survival in natural habitats by facilitating nutrient acquisition, stress adaptation, and disease suppression, while also offering opportunities to enhance crop productivity and climate resilience. However, the distribution of persistent and culturable bacteriome across maize-associated niches and their functional potential remain poorly resolved. This study integrated metagenomic next-generation sequencing (mNGS-based metabarcoding) and culturomics to characterise the maize-associated bacteriome of bulk soil, rhizoplane, phylloplane, and cob of the maize hybrid PHM-1 under contrasting cropping and tillage systems, and to identify recurrent and agriculturally promising bacteriome components. The bacteriome exhibited pronounced niche-specific structuring, whereas overall bacterial community composition did not differ significantly across cropping and tillage treatments (ANOSIM, <i>R</i> = 0.038, <i>p</i> = 0.306). Proteobacteria predominated in the culturable bacteriome (69–84%; mean, 76.2%) but accounted for only 1% of the total bacteriome, whereas Patescibacteria and Firmicutes were relatively enriched. Niche-specific dominance was evident, with <i>Pantoea</i> accounting for 40.79% of the total and 56.27% of the culturable phylloplane bacteriome under cereal monocropping, while <i>Serratia</i> represented 31.59% and 59.40% of the total and culturable cob bacteriomes, respectively. Across niches, mNGS captured substantially greater bacteriome diversity, particularly uncultured and unidentified taxa in soil-associated compartments, whereas culturomics recovered a narrower but functionally accessible fraction. Culturomics yielded 99 isolates representing 32 species across 12 genera, including six genera shared with the mNGS-derived recurrent bacteriome: <i>Bacillus</i>, <i>Enterobacter</i>, <i>Pantoea</i>, <i>Pseudomonas</i>, <i>Serratia</i>, and <i>Stenotrophomonas</i>. Functional screening identified strong biocontrol and plant-beneficial traits among core-associated isolates. <i>Pseudomonas oryzihabitans</i> ZM-DL-PA10 inhibited <i>Rhizoctonia solani</i>, <i>Macrophomina phaseolina</i>, and <i>Bipolaris maydis</i> by up to 40.6%, 43.9%, and 45.2%, respectively, through secreted and volatile metabolites; exhibited P, K, and Zn solubilisation; and produced IAA and siderophores. It also recorded the lowest <i>B. maydis</i> disease index (ADI) of 1.00. <i>Pantoea ananatis</i> ZM-BH-EA4 showed 52.4% and 68.5% inhibition of <i>R. solani</i> and <i>B. maydis</i>, respectively, through volatile metabolites. Collectively, the integration of mNGS and culturomics revealed a strongly compartmentalised maize bacteriome and identified recurrent, culturable, and functionally promising bacterial taxa, providing a targeted resource for microbiome-based crop protection and climate-resilient maize production.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"208 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response patterns of thermophilic Ascomycota to seasonal variations in Hammam Meskhoutine hot spring (Guelma, Algeria)","authors":"Wafa Chekiil,&nbsp;Sameh Belgacem,&nbsp;Randa Bouakkadia,&nbsp;Hamouda Babba,&nbsp;Skander E. Kadri,&nbsp;Tarek Merad","doi":"10.1007/s00203-026-05198-6","DOIUrl":"10.1007/s00203-026-05198-6","url":null,"abstract":"<div><p>Hot spring microbial mats may host diverse and thermally adapted fungal communities. This study investigated the environmental factors controlling the seasonal distribution of culturable fungi at the Hammam Meskhoutine hot spring. Culture-dependent morphological and molecular analysis identified three Ascomycota species: <i>Aspergillus fumigatus</i> (311 colonies), <i>Mycothermus thermophilus</i> (79 colonies), and <i>Thermomyces lanuginosus</i> (5 colonies). Significant density fluctuations were observed for <i>A. fumigatus</i> (<i>p</i> &lt; 0.001), which peaked in spring (13 × 10⁵ CFU g^− 1) before decreasing to a summer low (6 × 10³ CFU g^− 1). <i>M. thermophilus</i> showed a similar pattern (<i>p</i> = 0.049), reaching its maximum in winter (11 × 10³ CFU g^− 1) and a minimum in summer (2.2 × 10² CFU g^− 1). Principal component analysis indicated that a combination of macronutrients, trace elements, and physical and chemical parameters strongly correlate with this spatiotemporal occurrence. In vitro assays confirmed that temperature strictly dictates growth rates (Friedman test, <i>p</i> &lt; 0.001), defining clear thermal optima: 37 °C for <i>A. fumigatus</i> 50 °C for <i>M. thermophilus</i>, and 55 °C for <i>T. lanuginosus</i>, and thereby determining the ecological distribution of each isolate by shaping their distinct thermal niches. Furthermore, pH variations modulated these thermal preferences; notably, acidic conditions slowed <i>M. thermophilus</i> growth rates to 2.729 ± 1.82 mm days^− 1 even at its 37 °C optimum. More specifically, our observations suggest that the chemistry and temperature of the studied thermal water interact and affect the distribution patterns of the culturable fungi, and likely non-culturable fungi as well, within the same communities.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"208 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TOR kinase inhibition reverses azole resistance in Candida auris by targeting heme biosynthesis","authors":"Garima Gangwar,&nbsp;Biswambhar Biswas,&nbsp;Kartavya Mathur,&nbsp;Ankita Awasthi,&nbsp;Anil Thakur,&nbsp;Rekha Puria","doi":"10.1007/s00203-026-05203-y","DOIUrl":"10.1007/s00203-026-05203-y","url":null,"abstract":"<div><p>Antimicrobial resistance is a global menace, and multidrug-resistant fungal pathogens pose a serious global health threat. With limited numbers of antifungals available and the emergence of pan-drug-resistant strains, combating fungal infections has become increasingly challenging. Iron homeostasis is known to influence antifungal susceptibility. However, the role of heme, an iron-containing cofactor, in drug resistance remains poorly understood. We investigated the contribution of heme dynamics to acquired azole tolerance and evaluated the therapeutic potential of targeting heme biosynthesis and homeostasis in <i>Candida auris</i> (<i>C. auris</i>). We show that Hemin confers stress-specific protection in <i>C. auris</i>, rescuing growth and biofilm defects caused by Fluconazole (Flc) and the TOR kinase inhibitor Torin2. Transcriptomic analysis revealed that Torin2 in <i>C. auris</i> induces autophagy, represses global translation, and redirects glutamate metabolic flux. Growth complementation assays and quantitative gene expression experiments confirmed that glutamate metabolic flux is redirected towards glutamine biosynthesis via Gln1 activation rather than TCA-cycle participation via Gdh2. This and <i>Hem1</i> downregulation lead to reduced heme biosynthesis by Torin2. Flc, however, increases heme biosynthesis. Flc binds to the heme moiety of Erg11; hence, increased heme biosynthesis helps buffer Flc. Hemin or 5-ALA supplementation partially rescued growth and restored porphyrin and heme levels. Notably, scavenged heme from Sheep Blood increased MICs for azoles and terbinafine, demonstrating heme-mediated drug tolerance. Importantly, combined Torin2 and Flc treatment reduces growth by downregulating heme exchange and drug efflux, highlighting a potential combinatorial strategy to overcome azole resistance in <i>C. auris</i>. This study highlights the crucial link between the TOR pathway and heme and ergosterol metabolism, which contributes to drug resistance. It proposes targeting heme dynamics as a promising avenue for combination antifungal therapies, potentially improving clinical outcomes against <i>C. auris</i> and other resistant fungal pathogens.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"208 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative RSM and ANN modeling for sustainable production and purification of fungal protease using agro-industrial residues under solid-state fermentation and its industrial applications","authors":"Duaa Qaiser,&nbsp;Quratulain Maqsood,&nbsp;Hifza Rahat,&nbsp;Muhammad Zubair Ali,&nbsp;Muhammad Irfan,&nbsp;Tahir Mehmood","doi":"10.1007/s00203-026-05186-w","DOIUrl":"10.1007/s00203-026-05186-w","url":null,"abstract":"<div><p>Proteases make up about 60% of the enzyme market, making them one of the most significant and vital classes of commercial and industrial enzymes. In this study, six fungal strains (<i>Aspergillus oryzae</i>,<i> A. fumigatus</i>,<i> A. niger</i>,<i> A. flavus</i>,<i> A. terreus</i>, and <i>Trichoderma harzianum</i>) were evaluated for their potential for protease production using solid-state fermentation (SSF). Screening of the fungal strains and low-cost substrates (wheat bran and banana peels) revealed that <i>A</i>. <i>fumigatus</i> and <i>A. oryzae</i> had the best protease-producing ability in terms of quality and quantity, while wheat bran supported the highest level of protease production. Response surface methodology (RSM) and artificial neural network (ANN) were used to optimize production parameters, including temperature, inoculum size, pH, moisture content, and substrate concentration. The maximum protease activity (228.2 U/mL) was achieved at pH 7.0, 30 °C temperature, 3.0 mL inoculum, 50% moisture content, and 5.0 g substrate concentration. The model was statistically significant (<i>p</i> &lt; 0.05) with coefficients of determination (R²) of 93.15% for RSM and 94.65% for ANN. Stepwise purification steps yielded maximum enzyme recovery at 80% ammonium sulfate saturation, increasing protease activity to 364 U/mL, with a 3.01-fold purification by gel chromatography. SDS–PAGE analysis confirmed enrichment of protease in the purified fraction. The purified protease exhibited maximum relative activity at 40 °C and pH 8. Its activity was enhanced in the presence of Ca²⁺and Zn²⁺ ions, whereas EDTA inhibited enzyme activity. Salt also had a negative effect on the activity of protease. Kinetic analysis resulted in a Vmax of 93.98 U/mg and a Km of 1.473 mg/mL based on nonlinear Michaelis-Menten regression. Furthermore, the protease demonstrated good compatibility with commercial detergents and enhanced blood stain removal. Another application revealed that in-house produced enzyme had good potential for removing the gelatin layer from waste X-ray films within 45 min. The outcomes highlight a cheap, sustainable, and economically viable approach for producing an industrially relevant protease through waste valorization.</p></div>","PeriodicalId":8279,"journal":{"name":"Archives of Microbiology","volume":"208 12","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}