MicrobiologyOpen[JOURNAL]
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200 papers
Phage Therapy as an Alternative Strategy Against Pseudomonas aeruginosa: A Narrative Review of Preclinical and Clinical Evidence.
Cunha GAD, Amaral RP, Dos Santos ALC … +5 more , Aio BRF, Durante MFR, Malaquias LCC, de Freitas Almeida GM, Coelho LFL
Microbiologyopen · 2026 Jun · PMID 42071311 · Full text
Pseudomonas aeruginosa is an opportunistic pathogen and one of the main causes of nosocomial infections. This pathogen affects immunocompromised individuals such as patients with chronic wounds or cystic fibrosis. Its ca...
Pseudomonas aeruginosa is an opportunistic pathogen and one of the main causes of nosocomial infections. This pathogen affects immunocompromised individuals such as patients with chronic wounds or cystic fibrosis. Its capacity to evade antimicrobial therapies through resistance mechanisms has resulted in widespread prevalence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) strains. We searched three databases (PubMed/Medline, Scopus, and Web of Science) for articles evaluating the effects of phage administration in the management of P. aeruginosa infections in animals and humans. We analyzed the main characteristics of the interventions, the coverage of different bacterial strains, and discussed possible gaps in the evidence available in the last 10 years. Literature shows strong evidence that the use of phage therapy for several clinical conditions in humans and animal models is a safe and effective intervention for infections caused by MDR/XDR/PDR P. aeruginosa. Despite its therapeutic potential, phage therapy still faces several limitations such as lack of standardized dosing protocols, inconsistent endotoxin quantification, and limited regulatory frameworks. Future guidelines should focus on the regulation and validation of phage therapy in clinical practice, after overcoming the limitations currently identified. Further studies should ensure the standardization of phage production and the validation of delivery systems and routes of administration. Conducting multicenter clinical trials can contribute to the clinical implementation of phage therapy in countries where it is not yet regulated.
Gut Microbiota as a Key Modulator in the Pathophysiology of Sepsis: SURVEIL Project.
Bazzano C, Caramaschi A, Massa N … +20 more , Collani S, Mellai M, Barizzone N, Rocchetti A, Bottino P, Caroppo MS, Bonato V, Vaschetto R, Scaglione S, Francese A, Gholami N, Caria C, Bianchi P, Lauritano C, Castello L, Roveta A, Maconi A, Andreoni S, Dalfonso S, Bona E
Microbiologyopen · 2026 Jun · PMID 42062801 · Full text
Sepsis is a life-threatening condition frequently associated with gut dysbiosis and bacterial colonization by multidrug-resistant organisms. However, the interplay between gut microbiota, colonization patterns, and sepsi...
Sepsis is a life-threatening condition frequently associated with gut dysbiosis and bacterial colonization by multidrug-resistant organisms. However, the interplay between gut microbiota, colonization patterns, and sepsis onset remains poorly defined. The authors analyzed longitudinal gut microbiota profiles from 132 hospitalized patients enrolled in the SURVEIL study. Rectal swabs were collected at three time points (baseline, sepsis onset, and discharge). Bacterial colonization status and MDR strains were determined through culture-based methods, while microbiota composition was assessed via 16S rDNA sequencing. Diversity indices, taxonomic and functional profiles, and differential abundance analyses (LEfSe) were integrated with clinical metadata, including age and sepsis status. At baseline, colonized patients-particularly those harboring Gram-positive taxa-exhibited significantly reduced alpha diversity compared to non-colonized individuals. Aging further modulated diversity and beta diversity patterns independently. Sepsis was associated with profound dysbiosis, characterized by enrichment in opportunistic genera (e.g., Finegoldia sp., Anaerococcus sp., Parabacteroides sp.), reduced microbial diversity, and distinct beta diversity trajectories. Functional predictions revealed enhanced representation of anaerobic metabolism, nitrogen/sulfur cycling, and host-adaptive traits in colonized states. MDR strains partially overlapped with bloodstream pathogens in septic patients, suggesting a possible link between intestinal colonization and bloodstream infection that warrants mechanistic validation. Our findings demonstrate that bacterial colonization and sepsis are strongly associated with compositional and functional shifts in the gut microbiota. Age and MDR carriage further shape microbiota dynamics. Early microbial signatures, such as Finegoldia sp. enrichment in colonized non-septic patients, may represent early markers of microbial destabilization and sepsis risk.
Genome-Wide In Silico Analysis of the Type VI Secretion System (T6SS) Within the Morganella Genus.
Duque M, Jacquemin A, Girlich D … +2 more , Bonnin RA, Dortet L
Microbiologyopen · 2026 Jun · PMID 42057589 · Full text
Morganella spp., part of the Morganellaceae family, are opportunistic pathogens commonly found in the human gut microbiota. They are highly adaptable, cause various types of infections, and are difficult to treat due to...
Morganella spp., part of the Morganellaceae family, are opportunistic pathogens commonly found in the human gut microbiota. They are highly adaptable, cause various types of infections, and are difficult to treat due to virulence factors and resistance genes. In 2017, Morganella became part of the WHO Bacterial Pathogen Priority List (BPPL). In 2024, a genomic study revealed significant differences between clinically relevant species, particularly between M. sibonii and M. morganii, with M. sibonii possessing a unique type VI secretion system (T6SS) operon. This study aimed to explore the distribution and diversity of T6SS in Morganella species. A retrospective analysis of 293 Morganella genomes from 1966 to 2023 was conducted. The T6SS clusters and subtypes were annotated using the SecReT6 platform and RAST, with phylogenetic analysis performed on tssB genes. Putative effectors and immunity proteins were identified through in silico analysis using BlastP and Alphafold. We identified that M. sibonii isolates possess four T6SS clusters of subtypes i1, i3 v.1, i3 v.2, and i5. In contrast, most M. morganii isolates lacked T6SS, with only one-third containing a subtype i1 T6SS. Notably, M. morganii frequently (95%, 117/123 effectors) harbored a T6SS-predicted TseV effector, while M. sibonii exhibited a greater diversity of effectors. This study highlights species-specific T6SS patterns among Morganella genus and suggests that T6SS might play a crucial role in bacterial lifestyle competition and host-pathogen interactions. It paves the way for future research on Morganella pathogenicity.
Synergistic Effects of IMP-1700, Ciprofloxacin, and X-Ray Radiation in Bacteria and Mammalian Cell Lines: Implications for Use in Antimicrobial-Resistant Bacteria.
Andersen IV, Sloth AB, Bøgestad ECS … +5 more , Poulie CBM, Clausen AS, Battisti UM, Herth MM, Kjaer A
Microbiologyopen · 2026 Jun · PMID 42041183 · Full text
IMP-1700 was developed as a compound designed to target bacterial DNA repair-associated pathways, including homologous recombination mediated by the AddAB/RecBCD system. While its antibacterial properties are well establ...
IMP-1700 was developed as a compound designed to target bacterial DNA repair-associated pathways, including homologous recombination mediated by the AddAB/RecBCD system. While its antibacterial properties are well established, the potential effects on mammalian noncancerous and tumor cells under genotoxic stress remain to be elucidated. This study investigates the impact of IMP-1700 and its synergistic effect in combination with ciprofloxacin (CPX) and X-ray radiation in bacterial cultures and mammalian cell lines. In Staphylococcus aureus (S. aureus), neither IMP-1700 (5 µM) nor CPX (15 µM) as monotherapy significantly reduced bacterial growth; their combination produced a substantial reduction in bacterial counts, and IMP-1700 further enhanced killing when combined with 10 Gy X-ray irradiation, resulting in a 77% decrease, demonstrating synergistic antibacterial activity. In mammalian cells, X-ray cytotoxicity was cell-type dependent: noncancerous NIH-3T3 fibroblasts showed no significant effect, while B16.F10 melanoma cells displayed delayed sensitivity, MDA-MB-231 breast cancer cells an intermediate response, and HepG2 hepatocellular carcinoma cells marked radioresistance. IMP-1700 enhanced radiation-induced cytotoxicity across all cell lines, particularly at 72 h post-irradiation. These findings suggest that although IMP-1700 was designed to target bacterial DNA repair pathways, it can enhance sensitivity to genotoxic stress in both bacterial and mammalian systems. Further mechanistic investigation and safety evaluation are required before potential therapeutic application.
Kefir: A Potential Gut Microbiota Modulator: A Systematic Review of Human Interventional Studies.
Hamsho M, Ranneh Y, Kaddour B … +5 more , Alfakhri S, Hacıbayram H, Shkorfu W, Terzi M, Fadel A
Microbiologyopen · 2026 Jun · PMID 42036973 · Full text
Kefir is a fermented dairy product containing live and active microbial culture, including lactic acid bacteria and yeast. Preclinical studies and narrative reviews have reported potential modulatory effects of kefir on...
Kefir is a fermented dairy product containing live and active microbial culture, including lactic acid bacteria and yeast. Preclinical studies and narrative reviews have reported potential modulatory effects of kefir on gut microbiota composition. Despite this, there isn't yet a thorough analysis of human intervention studies that fills this gap of research. Therefore, the aim of this review is to examine the role of kefir consumption on gut microbiota composition in humans. Comprehensive research was conducted using three major databases including Web of Science, PubMed, and Scopus. The risk of bias was assessed using Cochrane risk-of-bias tool and Risk of bias of non-randomized trials. The search resulted in 2743 studies, of which eight studies met our eligibility criteria. Overall, kefir resulted in minor changes in phyla and class levels. On the other hand, the Bifidobacterium genus increased in 3 out of 4 studies. Kefir-specific bacterial species and strains were found in participants fecal samples suggesting colonization properties. Kefir consumption was associated with modest and heterogenous changes in gut microbiota composition. Proposed mechanisms include transient persistent of kefir-associated taxa and modulation of the intestinal environment, although direct functional evidence in humans remains limited.
Using Selective Agar Containing Ciprofloxacin and Tetracycline Reveals Resistant Oral Microbiota in Healthy and Periodontitis Patients.
Wolf M, Metz J, Wittmer A … +7 more , Pelz K, Vach K, von Ohle C, Wolff D, Frese C, Cieplik F, Al-Ahmad A
Microbiologyopen · 2026 Apr · PMID 42026669 · Full text
The oral cavity may act as a reservoir for antibiotic resistance. This study aimed to directly isolate and identify phenotypically resistant bacteria from the oral biofilm of healthy individuals and patients with periodo...
The oral cavity may act as a reservoir for antibiotic resistance. This study aimed to directly isolate and identify phenotypically resistant bacteria from the oral biofilm of healthy individuals and patients with periodontitis, using tetracycline, and ciprofloxacin containing selective agar. Furthermore, resistance of selected bacteria towards ampicillin was also evaluated. Plaque samples were collected from 12 patients (six healthy, six with periodontitis). Bacteria were cultured on selective agar containg defined antibiotic concentration and non-selective media under aerobic and anaerobic conditions, identified by MALDI-TOF mass spectrometry and 16S rDNA sequencing. The selected bacteria were subsequently tested for susceptibility using disk diffusion, E-test, and β-lactamase assay. 495 strains representing 106 species were isolated, including 54 aerobes/facultative anaerobes and 52 obligate anaerobes. Antibiotic resistance was observed in all subjects: 15.2% of isolates were resistant to tetracycline, 32.9% to ciprofloxacin, and 0.6% to ampicillin, with no significant differences between healthy and periodontitis groups. Tetracycline resistance was most frequent in the Streptococcus mitis group and Eubacterium spp., while ciprofloxacin resistance was dominated by Actinomyces-Schaalia group. Concluding, prevalence of antibiotic-resistance was comparable between healthy and periodontitis patients. Resistance was most prevalent against ciprofloxacin and tetracycline, highlighting the oral cavity as a relevant reservoir for antibiotic resistance.
Vancomycin-Resistant Enterococcus in Wild Animals: A Global Scoping Review.
Nageye YA, Mude ASA, Bello KE
Microbiologyopen · 2026 Apr · PMID 42020960 · Full text
Antimicrobial resistance is a global One Health concern, and vancomycin-resistant Enterococcus (VRE) remains one of the clinically important resistant bacterial groups. Although VRE has been extensively studied in clinic...
Antimicrobial resistance is a global One Health concern, and vancomycin-resistant Enterococcus (VRE) remains one of the clinically important resistant bacterial groups. Although VRE has been extensively studied in clinical and livestock settings, it has been investigated far less often in free-ranging wild animals. This scoping review maps the published evidence on VRE in wild animals, with emphasis on reported prevalence, host and environmental correlates, anthropogenic exposures, and laboratory detection methods rather than quantifying pooled effect sizes. A structured search of PubMed, ScienceDirect, Scopus, Web of Science, and Google Scholar was conducted from database inception to the final search stage used for this review, with only peer-reviewed English-language primary studies contributing empirical wildlife VRE data included in the synthesis. Eligibility was guided by the Population-Concept-Context framework, and the mapped evidence included mammals plus one reptile study retained in the review scope. Twenty-five studies met the inclusion criteria. Most were conducted in Europe, with substantially fewer studies from Africa and South America, indicating major geographical gaps. Reported prevalence ranged from 1.08% in feral pigs in Brazil to 100% in wild rabbits in Spain, although several striking estimates were based on very small samples and should be interpreted cautiously. Culture-based methods were most frequently used, whereas PCR-based approaches were particularly useful for confirming resistance genes. Overall, the evidence suggests that wild animals can act as reservoirs or sentinels of VRE exposure in anthropogenically influenced environments. Standardized surveillance, clearer reporting, and broader One Health monitoring that explicitly includes wildlife are needed.
A Fluorogenic Biosensor for Direct Detection of Vibrio vulnificus, a Climate Change Biomarker.
Aranda MN, Caballos I, López-Palacios A … +6 more , Carmona-Salido H, Sanjuan E, Aznar E, Amaro C, Martínez-Máñez R, Hernández-Montoto A
Microbiologyopen · 2026 Apr · PMID 42013233 · Full text
Vibrio vulnificus, a marine pathogen and climate change biomarker, poses serious risks to human and animal health through seafood consumption and seawater exposure. Rapid detection methods are urgently needed for both vi...
Vibrio vulnificus, a marine pathogen and climate change biomarker, poses serious risks to human and animal health through seafood consumption and seawater exposure. Rapid detection methods are urgently needed for both vibriosis diagnosis and surveillance in warming coastal waters. We report a fluorogenic biosensor based on nanoporous anodic alumina loaded with rhodamine B and capped with an oligonucleotide probe targeting a unique sequence of the vvhA cytolysin gene, specific to V. vulnificus. In the presence of the target DNA, the probe is displaced, pores open, and the fluorophore is released, generating a measurable signal. The biosensor exhibited high sensitivity and selectivity across diverse matrices, including fish mucus and serum, human serum, sterilized brackish water, and-critically-unprocessed natural lake and seawater samples, without DNA extraction or amplification. Detection limits ranged between 10² and 5 × 10² CFU mL⁻¹, comparable in sensitivity to state-of-the-art qPCR assays. The biosensor outperformed conventional approaches in speed, simplicity, and cost-effectiveness, while maintaining accuracy. These findings underscore the potential of this platform for integrated One Health applications, bridging environmental monitoring with rapid diagnosis of vibriosis in humans and animals. Preliminary results from this study were previously made available as a preprint in SSRN (DOI: https://ssrn.com/abstract=5032822).
Antioxidant and Antibacterial Activities of Secondary Metabolites Produced by Streptomyces Isolates Against Extended-Spectrum β-Lactamase-Producing Bacteria.
Ali AS, Nageye YA, Bello KE
Microbiologyopen · 2026 Apr · PMID 42001329 · Full text
Extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria pose a severe therapeutic challenge globally. Streptomyces remain one of the most prolific natural sources of antibacterial and antioxidant secondary...
Extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacteria pose a severe therapeutic challenge globally. Streptomyces remain one of the most prolific natural sources of antibacterial and antioxidant secondary metabolites, yet their activity against ESBL-producing pathogens remains under-explored. Soil-derived Streptomyces isolates were screened for bioactivity, and the most potent strain (SM7) was identified by 16S rRNA sequencing. Secondary metabolites were extracted using ethyl-acetate and evaluated for antibacterial activity against ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae using agar diffusion, MIC, and MBC assays. Antioxidant activity was assessed using DPPH and ABTS assays, while GC-MS and molecular docking were employed to identify and characterize bioactive compounds. Streptomyces sp. SM7 exhibited strong antibacterial activity, producing inhibition zones of 21.4 ± 0.6 mm, 19.2 ± 0.4 mm, and 17.6 ± 0.5 mm against ESBL-producing E. coli, K. pneumoniae, and E. cloacae, respectively. MIC values ranged from 62.5 to 250 µg/mL, with bactericidal MBC/MIC ratios of 2. The extract showed potent antioxidant activity with DPPH and ABTS IC₅₀ values of 48.9 µg/mL and 61.4 µg/mL, respectively. GC-MS identified 18 bioactive compounds, with 2,4-di-tert-butylphenol (18.6%) as the major constituent, which exhibited a docking affinity of -7.1 kcal/mol against bacterial DHFR. Streptomyces sp. SM7 produces phenolic- and fatty-acid-rich metabolites with potent bactericidal and antioxidant activities against ESBL-producing pathogens, highlighting its promise as a natural source of next-generation antimicrobial agents. These findings support Streptomyces sp. SM7 as a promising lead for downstream purification, mechanism-guided optimization, and future drug-development efforts targeting difficult-to-treat ESBL-producing Enterobacterales.
Therapeutic Remodeling of the Gut Microbiome as a Strategy to Restore Immune Tolerance in Autoimmunity.
Boroumand B, Jaberi A, Zamani G … +7 more , Zandi E, Zare F, Vahedinezhad M, Abdollahi E, KarkonShayan S, GhazanfarAhari S, Sattar M
Microbiologyopen · 2026 Apr · PMID 42001402 · Full text
Autoimmune diseases happen when the immune system, which is supposed to defend the body from infections and other harmful things, starts to attack the body's own cells by mistake. In the last few years, they seem to be g...
Autoimmune diseases happen when the immune system, which is supposed to defend the body from infections and other harmful things, starts to attack the body's own cells by mistake. In the last few years, they seem to be getting more public, and the reasons are quite complicated. It is usually not just one factor, but a mix of genes and environmental influences, such as diet, infections, or even stress. The gut microbiome, the vast community of bacteria and other tiny organisms living in our intestines, plays an important role in shaping how the immune system behaves. When this gut microbiota becomes unstable (a state called dysbiosis), it can be associated with the onset or worsening of various autoimmune diseases. In this review, we discuss the close relationship between the gut microbiome and autoimmune disorders and focus on how the microbiome can affect immune activation, immune tolerance, and inflammation at the molecular level. The general idea is that, if we understand these interactions better, we might be able in the future to design new ways to manage autoimmune diseases earlier and maybe in a more personalized way. In the end, the review suggests that if we understand better how the microbiome is involved in autoimmune diseases, it might be possible in the future to design more personalized therapies that change gut bacteria in a smart way and hopefully improve patient outcomes.
Cargo Secreted by the Type IX Secretion System of Porphyromonas gingivalis Are Tethered to O-Lipopolysaccharides via a Pentasaccharide Linker.
Veith PD, Leeming MG, Chen YY … +1 more , Reynolds EC
Microbiologyopen · 2026 Apr · PMID 41992463 · Full text
The Gram-negative oral pathogen, Porphyromonas gingivalis, uses the Type IX Secretion System (T9SS) to secrete major virulence factors (cargo proteins) and anchor them to the cell surface via a novel linking sugar, 2-N-s...
The Gram-negative oral pathogen, Porphyromonas gingivalis, uses the Type IX Secretion System (T9SS) to secrete major virulence factors (cargo proteins) and anchor them to the cell surface via a novel linking sugar, 2-N-seryl, 3-N-acetylglucuronamide (SAGA), which is a component of a specific type of lipopolysaccharide, A-LPS. The reported structure of the polysaccharide component (A-PS) was a repeating phosphorylated mannan whereas the PS of conventional O-LPS (O-PS) is a repeating Gal-Glu-Rha-GalNAc unit. Here, we have performed extensive mass spectrometric analyses of cargo protein-linked LPS with and without proteinase K treatment to determine the structure of A-LPS. Limited acid hydrolysis of the PS backbone with trifluoromethanesulfonic acid enabled long PS fragments linked to cargo-derived peptides to be identified for the first time. Unexpectedly, rather than finding A-PS units, up to eleven O-PS repeating units were found linked to cargo via a novel pentasaccharide linker designated A-LS, composed of SAGA-Hex-dHex(CHO)(Pent)-Hex. In addition, samples from a wzzP/porT double mutant that produced free truncated O-PS were specifically hydrolyzed to cleave lipid A prior to MS analysis. In these samples A-LS was found attached to a limited number of O-PS repeating units that in turn were associated with a putative core oligosaccharide that included the LPS-specific sugar, 3-deoxy-d-manno-octulosonic acid (Kdo). The proposed structure of A-LPS explains all 11 genes specific to A-LPS biosynthesis, and provides the first structural evidence that cargo proteins such as the gingipains are anchored to the cell surface via a complete LPS molecule.
Maintenance of Gut Microbial Balance via the Kynurenine Pathway Improves Larval Performance and Resistance to Bacillus thuringiensis in Spodoptera exigua.
Pinos D, García-Marín E, Ramírez-Serrano B … +3 more , Benavent-Albarracín L, Gamir J, Crava CM
Microbiologyopen · 2026 Apr · PMID 41992430 · Full text
The gut microbiota is a key determinant of insect physiology, influencing nutrition, immunity, and interactions with plants and pathogens. In Lepidoptera, larval gut communities are dynamic, but a core microbiota, often...
The gut microbiota is a key determinant of insect physiology, influencing nutrition, immunity, and interactions with plants and pathogens. In Lepidoptera, larval gut communities are dynamic, but a core microbiota, often dominated by Enterococcus species, persists across instars. In Spodoptera littoralis, the enzyme kynurenine 3-monooxygenase (KMO) regulates gut bacterial composition via 8-hydroxyquinoline-2-carboxylic acid (8-HQA), a secreted iron-chelating compound. To investigate whether this mechanism is conserved in Noctuidae, we generated Spodoptera exigua kmo mutants using CRISPR/Cas9 and analyzed bacterial communities in foregut, midgut, hindgut, and oral secretions by 16S metabarcoding, using RNA-derived cDNA for gut samples and DNA for oral secretions due to lower microbial biomass. The kmo deletion abolished 8-HQA production, reduced bacterial diversity, and collapsed compartment-specific bacterial communities in the gut, while also being associated with Enterococcus dominance in oral secretions. Fitness assays revealed that kmo larvae exhibited reduced weight gain on artificial diet, and higher mortality and delayed growth when fed on pepper leaves. Moreover, kmo larvae were threefold more susceptible to Bacillus thuringiensis, consistent with an interaction between host physiological state, gut microbial homeostasis, and pathogen susceptibility. Dietary supplementation with 8-HQA partially mitigated, but did not fully rescue, growth deficits. Our results demonstrate that the kynurenine pathway and 8-HQA production are crucial for maintaining gut microbial homeostasis, particularly within Enterococcus, thereby supporting larval development, dietary adaptation, and pathogen resilience. These findings reveal a conserved mechanism in noctuid moths linking host metabolism, microbiota regulation, and ecological performance, emphasizing the interplay between host genetics, microbiota composition, and environmental stressors.
Nuclear Microautophagy Drives Vacuolar Targeting of Yeast Iron-Regulated Proteins During Lipid and Iron Limitation.
Jordá T, Puig S
Microbiologyopen · 2026 Apr · PMID 41988931 · Full text
Iron is an essential cofactor involved in cellular processes, including energy generation and the biosynthesis of DNA, proteins, and lipids. The limited solubility of iron at physiological pH frequently results in iron d...
Iron is an essential cofactor involved in cellular processes, including energy generation and the biosynthesis of DNA, proteins, and lipids. The limited solubility of iron at physiological pH frequently results in iron deficiency, thus necessitating sophisticated regulatory mechanisms to maintain iron homeostasis. In Saccharomyces cerevisiae, the transcription factor Aft1 mediates the early response to iron limitation by accumulating in the nucleus and activating the iron regulon, a set of genes involved in iron uptake, utilization and sparing. One of Aft1 targets, CTH2, encodes for a protein that promotes iron economy by post-transcriptionally downregulating non-essential iron-dependent pathways. Yeast cells that exhibit defects in unsaturated fatty acid (UFA) biosynthesis, such as mga2Δ mutants, mislocalize Aft1 to the vacuole under iron-deficient conditions, which impairs activation of the iron regulon. In this study, we show that Cth2, but not other nucleo-cytoplasmic shuttling proteins, also accumulates in the vacuole under simultaneous UFA and iron deficiencies. The deletion of autophagy- and piecemeal microautophagy of the nucleus (PMN)-related genes, including ATG1 and NVJ1, prevents Aft1 vacuolar mislocalization. Furthermore, the subcellular distribution of Nvj1 supports PMN activation under these conditions. Despite preventing vacuolar accumulation, these mutations do not restore the regulatory functions of Aft1 and Cth2, nor do they rescue growth in low-iron conditions. These findings suggest that PMN selectively targets non-functional iron-regulated proteins for degradation when both iron and UFA levels are limiting, serving as a quality control mechanism rather than a pathway for functional recovery. These findings underscore a regulatory layer coordinating nutrient sensing and protein turnover.
Investigation of Recombinantly Produced Endolysins Reveals a Modular Enzyme Shared by Several Enterobacteria Phages to Exhibit Broad-Range Lytic Activity Against Different Orders of Gammaproteobacteria.
Kazaka T, Zrelovs N, Akopjana I … +4 more , Bogans J, Jansons J, Dislers A, Kazaks A
Microbiologyopen · 2026 Apr · PMID 41987735 · Full text
Endolysins or murein hydrolases are hydrolytic enzymes produced by bacteriophages to cleave the host's cell wall during the final stage of the lytic cycle. Whereas globular endolysins are composed of a single enzymatical...
Endolysins or murein hydrolases are hydrolytic enzymes produced by bacteriophages to cleave the host's cell wall during the final stage of the lytic cycle. Whereas globular endolysins are composed of a single enzymatically active domain (EAD), modular endolysins have at least two recognizable modules, often comprising a cell wall binding domain coupled to an EAD. Although such enzymes seem to be rarer, their activity often exceeds that of their globular counterparts. Here, we explored five previously uncharacterized modular endolysins for their expression, purification, and activity against a panel of distinct environmental Gram-negative bacteria. Out of the selected endolysins derived from Enterobacteria-infecting phages, two were soluble and were purified to near homogeneity. Among them, endolysin shared by several Enterobacteria phages, referred to as El1, exhibited a notable bacteriolytic activity not only from within, but also from without the cells. The effects of the studied enzyme on bacterial growth and viability were studied in detail in Escherichia coli. Visual inspection of the treated cells verified that the enzyme could penetrate the E. coli cell membrane when applied exogenously. Interestingly, El1 was active in the absence of ethylenediaminetetraacetic acid (EDTA) against multiple environmental Gram-negative bacteria representing different Gammaproteobacteria orders. Although the exact Gram-negative lysis mechanism of El1 remains unknown, the breadth of its target range suggests El1 as a promising candidate for future studies to scrutinize natural endolysin interactions differences against evolutionary distinct bacteria.
Genomic Insights Into a Hospital-Acquired High-Risk Vancomycin-Resistant Enterococcus faecium Outbreak in Guangdong, China.
Guo Y, Zhuo C, Zhang T … +6 more , Wu K, Shi Z, Zhu Y, Huang J, Zhuo C, Qi N
Microbiologyopen · 2026 Apr · PMID 41975241 · Full text
A comprehensive molecular epidemiological study was conducted on a vancomycin-resistant Enterococcus faecium (VR-Efm) outbreak in Guangdong, China, with the aim of analyzing transmission routes and antimicrobial resistan...
A comprehensive molecular epidemiological study was conducted on a vancomycin-resistant Enterococcus faecium (VR-Efm) outbreak in Guangdong, China, with the aim of analyzing transmission routes and antimicrobial resistance patterns, developing specific diagnostic tools for early detection, and elucidating genetic relationships with previously reported strains. Strain identification was performed using matrix-assisted laser desorption/ionization mass spectrometry, whereas whole-genome sequencing was performed for bacterial genomic characterization. Comprehensive bioinformatic analyses, including multilocus sequence typing, phylogenetic tree construction, principal component analysis, minimum spanning tree, and comparative genomic analyses, were performed. Our genomic investigation identified as predominant the sequence type 80 strain of VR-Efm, which exhibited a high level of resistance to a range of antibiotics, particularly vancomycin, amoxicillin, and teicoplanin. Through genome sequencing, we established genetic proximity between the outbreak strain and those previously identified in India and Japan. Furthermore, functional genomic analyses have elucidated genetic variations within critical genes, such as rsmH, which may be associated with the acquisition of antibiotic resistance. The identification of unique molecular markers within the outbreak strain facilitated the development of specific PCR assays, thereby significantly enhancing our capacity for early and precise detection of VR-Efm. Our in-depth genomic analysis of the VR-Efm outbreak in Guangdong, China, identified a predominant ST80 strain that exhibited multidrug resistance, especially to vancomycin. This finding underscores the need for enhanced global public health surveillance to address this emerging threat.
Porphyromonas gingivalis Suppresses Interferon-Gamma Signaling in Macrophages Through a Contact-Dependent, Gingipain-Mediated Mechanism.
Abe S, Ohshima J, Morita M … +2 more , Tanaka N, Hayashi M
Microbiologyopen · 2026 Apr · PMID 41968448 · Full text
Interferon signaling serves as a crucial defense mechanism for host cells against intracellular pathogens. Interferon-gamma (IFN-γ) binding to macrophages impacts the expression of approximately 2000 genes, activating th...
Interferon signaling serves as a crucial defense mechanism for host cells against intracellular pathogens. Interferon-gamma (IFN-γ) binding to macrophages impacts the expression of approximately 2000 genes, activating them to enhance intracellular bactericidal activity. While various immune evasion strategies of Porphyromonas gingivalis have been extensively studied, the specific mechanisms by which it suppresses IFN-γ-mediated macrophage activation remain insufficiently characterized. In this study, we elucidated the molecular mechanism by which P. gingivalis suppresses interferon signaling in macrophages, with a particular focus on STAT1 transcript abundance, because STAT1 encodes a central transcription factor in the IFN-γ pathway. RNA-seq analysis revealed that P. gingivalis infection reduced the mRNA abundance of approximately 41% of genes upregulated following IFN-γ stimulation, including STAT1 transcripts and other interferon-related genes. Further experiments showed that direct contact between the bacterium and host cells is necessary for this inhibition. This process involves the Type IX Secretion System (T9SS) and gingipains. Notably, strains lacking all gingipains (Kgp, RgpA, and RgpB) failed to suppress STAT1 transcript abundance and instead allowed nuclear translocation of phosphorylated STAT1. These gingipain-deficient strains also exhibited reduced invasive ability, correlating with their diminished capacity to suppress interferon signaling and macrophage activation. In conclusion, our findings demonstrate that P. gingivalis inhibits interferon signaling in macrophages through intracellular infiltration, with T9SS and gingipains playing essential roles in this immunosuppressive mechanism. These results provide valuable insights into the immune evasion strategies of P. gingivalis and suggest potential therapeutic targets for combating periodontopathic diseases.
The Influence of COVID-19 on the Composition and Drug Resistance of Pleural Effusion in Shandong Province.
Yu W, Ma S, Xu F … +9 more , Han X, Li M, Zhu Y, Pan S, Hou S, Ma C, Deng F, Wang S, SPARSS net Working Group
Microbiologyopen · 2026 Apr · PMID 41968297 · Full text
To analyze the composition and drug resistance changes of pleural effusion in Shandong region from 2017 to 2024, and to provide a basis for clinical empirical treatment and future public health strategies. Uese the WHONE...
To analyze the composition and drug resistance changes of pleural effusion in Shandong region from 2017 to 2024, and to provide a basis for clinical empirical treatment and future public health strategies. Uese the WHONET5.6 software to analyze the data reported by the SPARSS network. A total of 6336 pathogens was isolated, 3876 were Gram-positive bacteria and 2211 were Gram-negative bacteria. The top five pathogens are Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Streptococcus constellatus, and Escherichia coli. The main pathogens in male patients are S. constellatus, S. epidermidis, and K. pneumoniae, while in female patients, they are mainly S. aureus, S. epidermidis, and E. coli. The detection rate of S. constellatus rose from 4.3% to 8.1% after the COVID-19 pandemic (p < 0.0001); K. pneumoniae rose from 6.9% to 8.9%(p = 0.0264), and its resistance rate to meropenem increased from 2.1% to 18.3% (p = 0.0063). The detection rate of methicillin-resistant Staphylococcus aureus has remained largely unaffected by the COVID-19. The resistance rate of Candida albicans to fluconazole is as high as 12.5%. The pathogen spectrum of pleural effusion in Shandong Province is mainly Gram-positive bacteria. Coagulase-negative staphylococci were among the most common isolates, yet their role as true pathogens versus culture contaminants remains to be clarified in clinical practice. Moreover, after the epidemic, the carbapenem resistance of K. pneumoniae has significantly increased, and the problem of fungal drug resistance also needs to be paid attention to continuous monitoring to guide the rational use of drugs in clinical practice.
The Mechanism of Gut Microbiota in Breast Cancer Based on the Bulk Transcriptome, Mendelian Randomization Analysis and Single Cell RNA Sequencing.
Luo T, Xue M, Du Y … +3 more , Chen H, Sun Y, Sun H
Microbiologyopen · 2026 Apr · PMID 41960682 · Full text
Breast cancer (BC) is the leading cause of cancer death in women. Bidirectional regulation between BC and gut microbiota (GM) is established, but GM's mechanistic role in BC pathogenesis remains unclear. Public BC/contro...
Breast cancer (BC) is the leading cause of cancer death in women. Bidirectional regulation between BC and gut microbiota (GM) is established, but GM's mechanistic role in BC pathogenesis remains unclear. Public BC/control samples and GM genome-wide association study data underwent Mendelian randomization to identify GM-BC associations and GMRGs. DEGs between BC and controls were analyzed. Candidate genes were derived from intersecting DEGs and GMRGs. Machine learning identified biomarkers, validated by expression analysis. GSEA, immune infiltration, drug screening with molecular docking, and scRNA-seq were performed. Intersecting 3455 DEGs with GMRGs yielded eight candidates; MCM6 and NR3C1 were validated as biomarkers, enriched in DNA replication pathways. Immune infiltration showed 13 differential immune cells, with macrophages notably influencing biomarkers. Etoposide exhibited strong binding to biomarkers via docking. scRNA-seq identified epithelial cells as key, with stage-dependent biomarker expression. This study redefines BC as a microbiome-regulated network, identifying the MCM6/NR3C1 biomarker pair for early diagnosis and microbiome-targeted interventions.
Reduction of Hexavalent Chromium by Stenotrophomonas and Bacillus.
Husaini AF, Christita M, Rukmana RM … +2 more , Susilowati A, Vidilaseris K
Microbiologyopen · 2026 Apr · PMID 41957921 · Full text
Hexavalent chromium [Cr(VI)] is a widespread environmental pollutant, posing a significant health risk to ecosystems and humans. Bioremediation using microorganisms offers a cost-effective strategy for its detoxification...
Hexavalent chromium [Cr(VI)] is a widespread environmental pollutant, posing a significant health risk to ecosystems and humans. Bioremediation using microorganisms offers a cost-effective strategy for its detoxification. This review highlights recent advances in Cr(VI) reduction by Stenotrophomonas and Bacillus species, two bacterial genera with strong potential for chromium detoxification. Stenotrophomonas species primarily rely on intracellular enzymatic reduction mechanisms, often mediated by chromate reductases such as ChrR and heme proteins that link chromium detoxification with iron homeostasis. In contrast, Bacillus species employ a broader range of strategies, combining intracellular and extracellular enzymatic reduction, biosorption, and bioaccumulation, supported by stress-response and efflux systems that confer exceptional tolerance to Cr(VI). Comparative analysis reveals complementary metabolic strengths: Stenotrophomonas excels in rapid enzymatic detoxification, while Bacillus offers long-term stability through spore formation and surface-associated sequestration. Together, these traits underscore the promise of mixed consortia featuring both genera for scalable and resilient chromium bioremediation systems. Future research integrating omics-guided pathway mapping, microbial engineering, and biosafety control is expected to accelerate the deployment of efficient and safe Cr(VI) bioremediation technologies.
Dispersion Inhibits Thermal Mitigation of Pseudomonas aeruginosa Biofilms on Self-Heating Surfaces.
Parnian P, Zoga PK, Aljaafari HAS … +3 more , Chicchelly H, Toops M, Nuxoll E
Microbiologyopen · 2026 Apr · PMID 41940480 · Full text
Bacterial biofilms on medical implants are a major problem, typically requiring explantation and replacement of the biofilm-colonized implant. Thermal mitigation of these biofilms in situ has shown great promise in the l...
Bacterial biofilms on medical implants are a major problem, typically requiring explantation and replacement of the biofilm-colonized implant. Thermal mitigation of these biofilms in situ has shown great promise in the laboratory, where the thermal shock can be most precisely delivered by immersion in hot media. Clinical implementation requires delivering the shock from the implant surface, however, leaving the surroundings at a cooler temperature. This study hypothesized that bacteria may rapidly, reversibly disperse into the cooler surroundings to partially evade the shock and tested this hypothesis by thermally shocking Pseudomonas aeruginosa biofilms on thermoelectric devices under media with different heat sink conditions. The time scale and equilibrium constant of this dispersion were investigated in ambient temperature immersion studies, and the effect of thermal shock on bacterial dispersion rate was investigated in a flow cell using biofilms grown on thermoelectric devices. The results showed that biofilms equilibrate with surrounding media in seconds, that a small fraction of bacteria in the biofilm are much less prone to dispersion, that thermal shock triggers an immediate increase in dispersion, and that shocking biofilms via their substrate in cooler surrounding decreases shock efficacy compared to shocks where the surrounding's temperature approaches that of the substrate.
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