Chemistry & Biology[JOURNAL]
Sun
200 papers
Disrupting phage liquid crystalline droplets restores antibiotic susceptibility in Pseudomonas aeruginosa biofilms.
Tarafder AK, Graham M, Davis LK … +11 more , Pratt S, Böhning J, Manivannan P, Wang Z, Clemente CM, Weimann A, Floto RA, Owens RJ, O'Toole GA, Pearce P, Bharat TAM
PLoS Biol · 2026 Jun · PMID 42247470 · Full text
All bacterial biofilms contain an extracellular matrix rich in filamentous molecules that self-associate, conferring emergent properties to bacteria, including antibiotic tolerance. Pseudomonas aeruginosa is a human path...
All bacterial biofilms contain an extracellular matrix rich in filamentous molecules that self-associate, conferring emergent properties to bacteria, including antibiotic tolerance. Pseudomonas aeruginosa is a human pathogen that forms biofilms in diverse infectious settings, where the upregulation of a filamentous bacteriophage Pf4, has been shown to be a key virulence factor that protects bacteria from antibiotics. Here, we modeled biophysical characteristics of biofilm-linked liquid crystalline droplets formed by Pf4, which predicted that sub-stoichiometric phage binders had the ability to disrupt liquid crystals by changing the surface properties of the phage. We tested this prediction by developing nanobodies targeting the outer surface of the Pf4 phage, which disrupted in vitro reconstituted droplets, promoted antibiotic diffusion into bacteria, disrupted P. aeruginosa biofilm formation under a variety of conditions, and abolished antibiotic tolerance of biofilms. The inhibition strategy illustrated in this study could be extended to biofilms of other pathogenic bacteria, where filamentous molecules are pervasive in the extracellular matrix. Furthermore, our findings exemplify how targeting a biophysical mechanism, rather than a defined biochemical target, is a promising avenue for intervention, with the potential of applying this concept to other disease-related contexts.
Investigating substrate specificity in arogenate versus prephenate dehydratases.
Clayton EJ, Smith-Uffen M, Tribble TW … +2 more , Duennwald ML, Kohalmi SE
BMC Biol · 2026 May · PMID 42204708 · Full text
BACKGROUND: Phenylalanine is an essential aromatic amino acid that can only be synthesized de novo by microorganisms and plants. In microorganisms, phenylalanine is synthesized through the prephenate pathway, requiring t...
BACKGROUND: Phenylalanine is an essential aromatic amino acid that can only be synthesized de novo by microorganisms and plants. In microorganisms, phenylalanine is synthesized through the prephenate pathway, requiring the activity of a prephenate dehydratase (PDT). In plants, phenylalanine is synthesized instead mostly through the arogenate pathway, requiring the enzyme arogenate dehydratase (ADT). In Arabidopsis, there is a family of six ADTs that catalyze this final step of phenylalanine biosynthesis. However, two of the AtADTs, AtADT1 and AtADT2, can also act as PDTs. All six AtADTs have a high sequence similarity, making it difficult to determine in silico which amino acids determine substrate specificity. RESULTS: Here, we use domain swapping, targeted mutagenesis, and pha2 yeast complementation to investigate amino acids that confer PDT activity in pha2 yeast. In addition, we established a novel in vivo test of ADT activity to determine how these amino acid changes affect ADT and PDT activity of the AtADTs. CONCLUSIONS: Our results demonstrate that a combination of amino acids in the regulatory ACT domain contributes to both ADT and PDT activity in the AtADTs.
Improved tumor accumulation and photodynamic antitumor efficacy of a PEGylated photosensitizer.
Yoon H, Keum Y, Lee JE … +2 more , Chae YJ, Chang JE
J Photochem Photobiol B · 2026 Jul · PMID 42202710 · Publisher ↗
Photodynamic therapy (PDT) has emerged as a promising modality for cancer treatment; however, the clinical translation of many photosensitizers remains limited by poor aqueous solubility, unfavorable biodistribution, and...
Photodynamic therapy (PDT) has emerged as a promising modality for cancer treatment; however, the clinical translation of many photosensitizers remains limited by poor aqueous solubility, unfavorable biodistribution, and insufficient tumor accumulation. In this study, we investigated whether PEGylation of the photosensitizer Photomed could improve its physicochemical properties and in vivo photodynamic therapeutic efficacy without compromising its intrinsic photochemical activity. A PEG-conjugated Photomed (Photomed-PEG) was synthesized and systematically evaluated using singlet oxygen generation assays, cellular uptake studies, and in vitro phototoxicity assessments. In vivo biodistribution and antitumor efficacy were further examined in an A549 tumor-bearing mouse model. PEGylation markedly enhanced the aqueous solubility of Photomed while preserving efficient singlet oxygen generation and minimal dark toxicity. Moreover, Photomed-PEG exhibited enhanced tumor accumulation with reduced off-target retention compared to its non-PEGylated counterpart. These favorable pharmacokinetic properties translated into significantly improved photodynamic antitumor efficacy, as evidenced by pronounced tumor growth suppression following PDT. Importantly, no significant body weight loss or histopathological abnormalities in major organs were observed, indicating an acceptable safety profile. Collectively, these findings demonstrate that PEGylation represents an effective strategy for optimizing photosensitizer delivery and enhancing in vivo therapeutic performance for solid tumors.
IR783-enabled thioketal-bridged paclitaxel nanoprodrugs with ROS-responsive release for tumor imaging and chemotherapy.
Li Y, Wang H, Wu J … +5 more , Tian B, Sun Y, Chen M, Yuan Z, Gao J
J Photochem Photobiol B · 2026 Jul · PMID 42202709 · Publisher ↗
Paclitaxel (PTX), a potent chemotherapeutic agent, faces significant clinical limitations due to poor aqueous solubility, systemic toxicity, and non-specific biodistribution, particularly in advanced peritoneal metastase...
Paclitaxel (PTX), a potent chemotherapeutic agent, faces significant clinical limitations due to poor aqueous solubility, systemic toxicity, and non-specific biodistribution, particularly in advanced peritoneal metastases. To overcome these challenges, we developed a carrier-free, self-assembled theranostic nanoprodrug system, IPSP NPs, integrating a thioketal-bridged paclitaxel dimer (PSP) with the near-infrared (NIR) fluorophore IR783. This innovative design enables reactive oxygen species (ROS)-responsive drug release and simultaneous NIR imaging. Comprehensive characterization confirmed the formation of stable, monodisperse IPSP NPs (∼161 nm) with high encapsulation efficiencies for both PSP (∼72.4%) and IR783 (∼89.4%). In vitro studies demonstrated robust ROS-triggered PTX release from IPSP NPs and a "prodrug latency effect" in colon cancer cells, showcasing stability at low concentrations and high cytotoxicity at therapeutic levels. In vivo evaluations in a CT26-Luc1 murine peritoneal metastasis model revealed favorable biodistribution with sustained tumor accumulation and significant tumor suppression comparable to free PTX. Histopathological analysis (H&E, Ki-67, TUNEL) demonstrated profound tumor cell damage, induced apoptosis, and inhibited proliferation by IPSP NPs. Crucially, IPSP NPs exhibited superior biosafety profiles, evidenced by normal organ histologies and improved renal function (reduced uric acid levels) compared to free PTX, highlighting reduced off-target toxicity. This work establishes a promising strategy for polymer-free theranostic nanoparticles, offering enhanced tumor targeting, controlled drug release, imaging capabilities, and improved safety for cancer therapy.
An MMP-independent fluorescent probe for simultaneously detecting viscosity and hydrogen peroxide in tumor tissues of cancer patients.
He JY, Niu J, Jing P … +3 more , Li Y, Ma Y, Lv Z
J Photochem Photobiol B · 2026 Jul · PMID 42191405 · Publisher ↗
Elucidating the fundamental interrelation between hydrogen peroxide (HO)/viscosity and mitochondria related diseases still is a major issue due to the lack of an excellent tool for long-term tracking of mitochondrial vis...
Elucidating the fundamental interrelation between hydrogen peroxide (HO)/viscosity and mitochondria related diseases still is a major issue due to the lack of an excellent tool for long-term tracking of mitochondrial viscosity and hydrogen peroxide. Herein, we devised an MMP-independent probe, BKI, which could simultaneously detect fluctuations of viscosity and HO. BKI shows a good response to HO with a low detection limit of 34 nM, mediated by the specific reaction between HO and the borate ester moiety. Moreover, BKI can also monitor the viscosity fluctuations with green emission at 475 nm due to the rotation of its vinyl double bond. Notably, BKI not only localizes in mitochondria accurately but also firmly immobilizes in mitochondrial inner membrane through hydrophobic interactions between its long alkyl chains and lipids on the mitochondrial membrane, enabling long-term monitoring mitochondrial viscosity and HO. Using BKI, the viscosity changes induced by monensin or nystatin, as well as exogenous and endogenous HO in living cell were successfully visualized. In particular, the unique probe can distinguish between normal tissues and tumor tissues of cancer patients by detecting viscosity and HO. These results imply that BKI can be served as a powerful tool for long-term visualizing mitochondrial viscosity and HO in vitro and in vivo.
Label-free fluorescence lifetime imaging of cells nuclei: A sensitive readout of metabolic response.
Gorbunova IA, Nikonova EE, Shirmanova MV … +5 more , Shcheslavskiy VI, Komarova AD, Druzhkova IN, Timashev PS, Shirshin EA
J Photochem Photobiol B · 2026 Jul · PMID 42191404 · Publisher ↗
Fluorescence lifetime imaging microscopy (FLIM) using endogenous fluorescence of NADH (reduced nicotinamide adenine dinucleotide) and its phosphorylated form NADPH represents a powerful tool for monitoring cellular metab...
Fluorescence lifetime imaging microscopy (FLIM) using endogenous fluorescence of NADH (reduced nicotinamide adenine dinucleotide) and its phosphorylated form NADPH represents a powerful tool for monitoring cellular metabolic states. For a more nuanced interpretation of the FLIM data, investigating NAD(P)H in different cell compartments is crucial. In this study, we demonstrate that a weak NAD(P)H fluorescence in cell nuclei, which is often ignored, can be reliably analyzed using a phasor plot approach and provides a sensitive readout of metabolic responses. Using colorectal cancer cells HCT116 treated with the metabolic inhibitors rotenone and 3-bromopyruvate, as well as the chemotherapeutic agent 5-fluorouracil (5-FU), we show that nuclear NAD(P)H fluorescence decay changes in response to treatment. In the case of 5-FU, the phasor analysis of nuclear NAD(P)H reveals heterogeneous cellular responses with two subpopulations differing in NAD(P)H fluorescence decay parameters, fluorescence intensity, and cytoplasm-to-nucleus intensity ratio. Notably, nuclear and cytoplasmic responses are strongly correlated, indicating tight coupling of their NAD(P)H pools. Overall, our results establish nuclear NAD(P)H fluorescence as a robust, label-free indicator of cellular metabolism and highlight its potential for metabolic monitoring in conditions where analysis of NAD(P)H fluorescence is limited by spectral overlap with exogenous fluorescent labels.
From germline immortality to somatic rejuvenation: Unlocking the ovarian blueprint for longevity.
Chiavellini P, Sebastiano V
PLoS Biol · 2026 May · PMID 42189781 · Full text
Aging is typically framed as a one-way, irreversible accumulation of molecular damage in cells and tissues, leading to progressive functional decline. Yet mammalian reproduction, and particularly female reproduction, rev...
Aging is typically framed as a one-way, irreversible accumulation of molecular damage in cells and tissues, leading to progressive functional decline. Yet mammalian reproduction, and particularly female reproduction, reveals a striking exception to this rule. Despite residing within an aging organism and within a fast-aging ovarian tissue environment, oocytes give rise to embryos that begin life with restored developmental potential and youthful molecular organization. By reframing ovarian biology as a model for rejuvenation rather than solely as a site of reproductive decline, this Essay proposes that the ovary offers a powerful blueprint for advancing the biology of aging and longevity.
How Acquires and Interacts with Its Microbiome Across Ecological Contexts.
Ernstberger H, Palmieri G, Sun JS
Biology (Basel) · 2026 May · PMID 42187739 · Full text
Spotted wing drosophila (; SWD) has become a globally invasive pest by ovipositing in ripening, intact fruit rather than decaying material, a niche distinct from most other drosophilids. An expanding body of work implica...
Spotted wing drosophila (; SWD) has become a globally invasive pest by ovipositing in ripening, intact fruit rather than decaying material, a niche distinct from most other drosophilids. An expanding body of work implicates microbes and microbially derived chemistry as key drivers of this ecology, shaping fly biology across life stages. However, much of this evidence is derived from microbiome surveys and observational comparisons, further constrained by uncontrolled diet history, laboratory rearing, and insufficient ecological context. We examine how the SWD microbiome differs in which taxa are present (composition), how flies pick up those taxa from fruit and maternal sources (acquisition), how long those taxa are retained across life stages (persistence), and how each of these varies with diet, geography, season, and host crops. We then address how microbial cues and fermentation state function as context-dependent drivers of adult attraction, avoidance, and oviposition, and how microbe-mediated interspecific interactions reshape substrate suitability and competition among drosophilids. Throughout, we critically evaluate experimental designs and identify gaps that impede causal inference. These include limited strain-level resolution, incomplete fungal characterization, and weak linkages between microbial community structure and host phenotypes. Key unresolved questions include how SWD maintains performance across diverse hosts, how microbes modulate sensory processing during seasonal shifts, and which microbial metabolites drive attraction, avoidance, and competition. Resolving these questions is a direct prerequisite for field-stable integrated pest management (IPM), including microbially informed behavioral lures, oviposition deterrents derived from pathogen- and competitor-associated volatiles, and competitor-mediated suppression strategies. The experimental priorities identified here translate directly into a roadmap for the next generation of mechanistically grounded, ecologically realistic SWD management tools.
Sperm Antioxidant Capacity Discriminates Between Fertile and Infertile Men and Is Strictly Related to Lipid Peroxidation and Lipid Mediator Production.
Signorini C, Moretti E, Liguori L … +4 more , Leoni E, Marcucci C, Salvatici MC, Collodel G
Biology (Basel) · 2026 May · PMID 42187722 · Full text
Oxidative stress (OS) and inflammation are common causes of male infertility; antioxidants in spermatozoa and especially in seminal plasma play a protective role. The study aims to evaluate whether OS lipid mediators (F-...
Oxidative stress (OS) and inflammation are common causes of male infertility; antioxidants in spermatozoa and especially in seminal plasma play a protective role. The study aims to evaluate whether OS lipid mediators (F-isoprostanes: F-IsoPs; Resolvin D1: RvD1) measured in seminal plasma, and Trolox equivalent antioxidant capacity (TEAC), measured in both seminal plasma and spermatozoa, are associated with male infertility. Semen samples (18 fertile and 62 infertile subjects) were examined following WHO guidelines and with a mathematically elaborated transmission electron microscopy analysis (fertility index-FI-, % sperm pathologies). F-Isops were measured by GC/NICI-MS/MS, RvD1 by ELISA, and TEAC by a commercially available antioxidant assay. F-Isops, RvD1, and sperm TEAC (positively interrelated with each other) correlated negatively with seminal parameters and FI and positively with sperm pathologies. F-Isops, RvD1, and sperm TEAC levels were significantly higher in infertile vs fertile subjects ( < 0.001). ROC curve analysis demonstrated that sperm TEAC (J index: 0.13 mM) and seminal RvD1 (J index: 38.26 pg/mL) discriminated between fertile and infertile subjects. Spermatozoa stimulate antioxidant capacity in the presence of an OS environment; this data suggests an association in which antioxidant defences may vary in relation to the surrounding seminal plasma. Moreover, sperm TEAC, and to a lesser extent seminal RvD1, emerge as potential markers for identifying infertile patients.
Nutritional Assessment of Polish Middle-Distance Runners: Analysis of Biochemical Parameters and Antioxidant Status-Pilot Study.
Chrustek A, Przybylska A, Pakuła O … +5 more , Proszowska A, Filarecka A, Dombrowska-Pali A, Olszewska-Słonina D, Koba M
Biology (Basel) · 2026 May · PMID 42187699 · Full text
This study aimed to examine the nutrient intake in Polish middle-distance runners. The secondary objective was to examine the biochemical profile and antioxidant status in the blood serum of the runners, and then compare...
This study aimed to examine the nutrient intake in Polish middle-distance runners. The secondary objective was to examine the biochemical profile and antioxidant status in the blood serum of the runners, and then compare to the control group. The research was conducted among 44 volunteers. Information regarding participants' diet was gathered for three days before the study took place. Also, blood serum of athletes and control subjects was examined to obtain information about their antioxidant status, biochemical parameters, and micro- and macronutrients. This study showed that runners consumed more protein, sodium, zinc, phosphorus, water, vitamin A and E than the control group. The daily intake of selected vitamins, micro- and macronutrients in a group of athletes is approximately two times higher than in the control group. The control group consumed more polyphenols compared to the runners group ( < 0.05). The consumption of phenols was almost two times lower among runners compared to non-runners. The higher uric acid concentration ( = 0.025) and lower chloride concentration ( = 0.011) were observed in the blood serum of runners compared to the control group. The diet of middle-distance runners is well-balanced but need some modifications, especially regarding the intake of vitamin E, folates and polyphenols.
Anion and neutral-state bioluminescence reactions induced by imidazopyridine oxidation: Both identified as charge-transfer-induced luminescence (CTIL) from a density functional theory perspective.
Wu N, Xin YX, Xu ZC … +1 more , Bai YH
J Photochem Photobiol B · 2026 Jul · PMID 42184468 · Publisher ↗
Bioluminescence, generated through the luciferase-catalyzed oxidation of luciferin, produces visible light and is widely used in biomedical imaging and related fields. Imidazopyridine (ImPy) constitutes the core luminesc...
Bioluminescence, generated through the luciferase-catalyzed oxidation of luciferin, produces visible light and is widely used in biomedical imaging and related fields. Imidazopyridine (ImPy) constitutes the core luminescent scaffold of coelenterazine-type fluorophores, and its oxidation yields an anionic dioxetanone intermediate that typically undergoes cleavage. This process generally involves charge transfer between substituents and the formation of radical electrons, a phenomenon known as charge-transfer-induced luminescence (CTIL). The anionic dioxetanone can also be converted to its neutral form through protonation or intramolecular bonding. Although neutral dioxetanone can likewise undergo cleavage accompanied by charge transfer between substituents, the transferred charge is small. It has therefore often been overlooked, leading to the prevailing assumption that neutral-state cleavage does not belong to the CTIL category. The mechanistic distinction between these two cleavage modes remains unresolved. In this work, an ImPy model was constructed based on the structures of coelenterazine and furimazine, two representative marine luciferins. Using density functional theory (DFT), we computed the oxidation pathway leading to dioxetanone formation and examined its cleavage under various anionic and neutral states. Charge-transfer behavior and reaction barriers were evaluated, and wavefunction analyses were performed to visualize the evolution of radical-electron distribution and atomic interactions throughout the reaction. Our results show that although the amount of charge transferred between substituents in the neutral state is small, it remains essential, as these subtle charge shifts initiate dioxetanone cleavage. Neutral-state cleavage should therefore be classified as part of the CTIL mechanism, consistent with the anionic case. In both neutral and anionic states, the reaction is triggered by the transfer of negative charge to the central CCOO four-membered ring, and this transferred charge induces dissociation of the two oxygens, thereby initiating dioxetanone cleavage. In the anionic state, the pyrazinamine (PMN) moiety, which carries a substantial negative charge adjacent to CCOO, acts as the donor. The donated charge initially drives the separation of the two oxygen atoms within CCOO, subsequently propagates through the dioxetanone framework, induces cleavage of the C-C bond, and ultimately results in dioxetanone dissociation. In the neutral state, the only available donor is a single carbonyl oxygen atom, and the donated negative charge is sufficient only to separate the two oxygen atoms but insufficient to cleave the C-C bond of the CCOO ring. Additional energy is therefore required to amplify charge transfer and achieve full C-C bond rupture. By varying the initial negative charge load on the donor moiety, we further identified that a higher negative charge facilitates transfer to CCOO and thereby lowers the reaction barrier.
Influence of Er:YAG laser activation and hydrogen peroxide concentration on esthetic efficacy, peroxide kinetics, diffusion, and thermal response during dental bleaching.
Strazzi-Sahyon HB, Esteves LMB, Aidar KMS … +5 more , Junior FC, Neto FC, Correa JAC, Silva MGT, Briso ALF
J Photochem Photobiol B · 2026 Jul · PMID 42176586 · Publisher ↗
BACKGROUND: Laser-assisted in-office bleaching has been proposed to enhance whitening efficacy by accelerating hydrogen peroxide (H₂O₂) degradation and optimizing oxidative reactions. Nevertheless, Er:YAG laser influence...
BACKGROUND: Laser-assisted in-office bleaching has been proposed to enhance whitening efficacy by accelerating hydrogen peroxide (H₂O₂) degradation and optimizing oxidative reactions. Nevertheless, Er:YAG laser influence on thermal behavior, peroxide kinetics, optical performance, and trans-amelodentinal diffusion remains insufficiently elucidated. Thus, this in-vitro study evaluated the combined effects of Er:YAG laser activation and different H₂O₂ gel concentrations on thermal, chemical, and optical responses during enamel bleaching. METHODS: 186 bovine incisors were allocated into six groups according to H₂O₂ concentration (9%, 17.5%, and 35%) and Er:YAG irradiation (with or without activation). Phase I assessed temperature at the enamel surface and pulp chamber, and H₂O₂ degradation at distinct evaluation periods. Phase II evaluated chromatic alteration (ΔE), whitening index (WI) in relation to established perceptibility and acceptability thresholds, and trans-amelodentinal diffusion of H₂O₂. Statistical analyses were performed using ANOVA followed by Tukey post hoc tests (α = 0.05). RESULTS: Higher H₂O₂ concentrations resulted in significantly greater ΔE and WI values; however, these effects were accompanied by increased temperature and peroxide diffusion. Notably, comparisons between the highest and lowest H₂O₂ gel concentrations, irrespective of laser irradiation, exceeded the established whitening perceptibility threshold. Er:YAG irradiation significantly accelerated H₂O₂ degradation and enhanced whitening outcomes compared with non-irradiated groups. Notably, laser activation reduced trans-amelodentinal peroxide diffusion across all evaluated H₂O₂ gel concentrations. Overall, reductions in temperature and H₂O₂ gel concentration were observed over time. CONCLUSIONS: Er:YAG-assisted bleaching modulates peroxide degradation kinetics, enhances whitening efficacy, and influences thermal and trans-amelodentinal peroxide diffusion.
Evidence of visual learning and wavelength differential responses in three podocopids (Crustacea: Ostracoda).
Bellavere E, Mesquita-Joanes F, Romano D … +1 more , Rossetti G
BMC Biol · 2026 May · PMID 42163323 · Full text
BACKGROUND: Ostracods are small bivalved crustaceans that inhabit a wide range of aquatic environments, from fully marine to brackish and freshwater systems. All non-marine species belong to the order Podocopida. The sen...
BACKGROUND: Ostracods are small bivalved crustaceans that inhabit a wide range of aquatic environments, from fully marine to brackish and freshwater systems. All non-marine species belong to the order Podocopida. The sensory biology and behavioral capacities of ostracods remain poorly understood, even though these traits play pivotal roles in habitat exploration, food searching, mate recognition, and predator avoidance. In particular, studies addressing vision and learning ability are still scarce. Although visual structures in ostracods are often reduced or simplified, they exhibit considerable variation across taxa. In this study, we investigated the photoreceptive capabilities of three podocopid species, Vizcainocypria viator, Loxoconcha elliptica, and Xestoleberis nitida, representing different families. Using miniaturized, three-chamber lab-on-a-chip arenas, we examined both innate and experience-dependent light-guided behaviors, testing whether differential wavelength sensitivity and learned associations are present, if these traits are species-specific, and which locomotory responses are associated with them. RESULTS: Our results provide evidence for a simple form of long-term associative memory in ostracods, together with species-specific responses to conditioning type, light wavelength, and possibly light intensity. These responses were not restricted to spatial preferences among arena chambers, but also affected locomotory behavior. CONCLUSIONS: These findings highlight ostracods as valuable model organisms for studying fundamental biological processes such as sensory integration, behavioral plasticity, and learning. More broadly, this research advances our understanding of sensory evolution in crustaceans and sheds new light on the behavioral complexity of small aquatic invertebrates.
Environmental redox conditions and strain variation define phenazine-mediated antagonism in co-infecting bacteria.
Todd K, Schneider O, Lawrence JM … +12 more , Aronoff JL, Witek B, Velázquez-Colón V, Santana-Ufret V, Anderson NL, Gunter K, Noda M, Relich RF, Zeng L, Limoli DH, Whidbey C, Vornhagen J
PLoS Biol · 2026 May · PMID 42160385 · Full text
Pseudomonas aeruginosa and Klebsiella pneumoniae are gram-negative opportunistic pathogens that frequently colonize the human body and are major causes of infection. These bacteria are often co-isolated in polymicrobial...
Pseudomonas aeruginosa and Klebsiella pneumoniae are gram-negative opportunistic pathogens that frequently colonize the human body and are major causes of infection. These bacteria are often co-isolated in polymicrobial urinary tract and lung infections, the latter of which is associated with increased disease severity and worse clinical outcomes. Despite their overlapping niches and clinical relevance, little is known about how these two pathogens interact and how those interactions influence human health. Given the growing recognition that microbial interactions are key drivers of disease, we investigated how P. aeruginosa and K. pneumoniae influence one another. We discovered an antagonistic interaction in which P. aeruginosa restricts the growth of K. pneumoniae. This inhibition is driven by phenazine production in P. aeruginosa, specifically the secondary metabolites pyocyanin and pyorubin, which are both necessary and sufficient to suppress K. pneumoniae growth. Using a diverse set of clinical isolates, we found that this antagonism is strain-dependent. Both the susceptibility of K. pneumoniae to phenazines and the ability of P. aeruginosa to restrict K. pneumoniae growth varies between strains. Moreover, the necessity of phenazine production is specific to the site of infection. Together, these findings demonstrate that strain background and environmental context are critical determinants of pathogen interactions. These findings reveal that both strain background and environmental redox conditions govern the ecological rules of pathogen interaction, providing a framework for predicting outcomes.
The Pseudomonas aeruginosa ribonuclease Ribocin cleaves eukaryotic ribosomes at helix 69 to inhibit host translation.
Vasquez-Rifo A, Susorov D, Sholi EH … +6 more , Demo G, Jami Y, Sha J, Wohlschlegel JA, Korostelev A, Ambros V
PLoS Biol · 2026 May · PMID 42160310 · Full text
Pseudomonas aeruginosa employs host translation inhibition as a virulence-enhancing strategy. We previously showed that the bacterium induces cleavage of Caenorhabditis elegans large ribosomal RNA at helix 69 (H69), part...
Pseudomonas aeruginosa employs host translation inhibition as a virulence-enhancing strategy. We previously showed that the bacterium induces cleavage of Caenorhabditis elegans large ribosomal RNA at helix 69 (H69), part of a central intersubunit bridge and the ribosomal decoding center. In this study, we demonstrate that a previously uncharacterized ribonuclease, Ribocin, is necessary and sufficient for H69 cleavage. Recombinant Ribocin cuts H69 in worm and mammalian ribosomes, indicating that H69 cleavage by P. aeruginosa is phylogenetically conserved. In worms, mammalian cells, and rabbit reticulocyte lysates, H69 cleavage results in translation inhibition. Furthermore, Ribocin contributes to bacterial virulence toward C. elegans, triggers a major host response to translation inhibition, and operates in parallel with Exotoxin A-mediated translation inhibition. These findings unveil the first known nuclease that cleaves eukaryotic ribosomes at H69 and expand the understanding of host translation-inhibition by establishing targeted rRNA cleavage as a mechanism of host attack.
Symbiotic bacteria may support calcium carbonate precipitation in the Gulf toadfish.
Bonacolta AM, Kravitz T, Mozo R … +4 more , Baker LJ, Heuer RM, Grosell M, Del Campo J
PLoS Biol · 2026 May · PMID 42149909 · Full text
Marine fish play a significant yet understudied role in the oceanic carbon cycle through the production of magnesium-rich calcium carbonate (CaCO3) precipitates known as ichthyocarbonates. These deposits form in the gut...
Marine fish play a significant yet understudied role in the oceanic carbon cycle through the production of magnesium-rich calcium carbonate (CaCO3) precipitates known as ichthyocarbonates. These deposits form in the gut of marine teleost fish in response to salinity, serving as part of their osmoregulation strategy. Through this, marine fish may contribute as much as 9.04 Pg of CaCO3 per year in global new carbonate production, being equivalent to or potentially higher than the production by coccolithophores and pelagic foraminifera. Despite their ecological relevance, the biological mechanisms driving ichthyocarbonate precipitation remain to be fully resolved. Intriguingly, bacteria are consistently found in intimate association with ichthyocarbonate precipitates. Given the widespread capacity of prokaryotes to mediate CaCO₃ precipitation, this association points to a previously unexplored microbial contribution to the process. To investigate the potential role of bacteria in ichthyocarbonate production, we subjected Gulf toadfish (Opsanus beta) to salinity treatments common to their native range and known to elicit changes in CaCO3 precipitation. To assess the respective contributions of the host and its microbiota to ichthyocarbonate formation in the gut, we characterized the microbiome across the toadfish gut and performed meta-transcriptomic analysis. Across the toadfish gut, we identify a high abundance of vibrios associated with ichthyocarbonates with the metabolic potential for CaCO3 precipitation. Specifically, we observe the expression of the transcriptional activator of urease (ureR) by Photobacterium damselae subsp. damselae, which can induce the precipitation of CaCO3 via the production of bicarbonate. We demonstrate that CaCO₃ precipitation in marine fish may not solely be a host-driven process, but potentially the result of a functional symbiosis with gut-associated Vibrio bacteria. We hypothesize that just as photosymbionts enable corals to build reefs, fish hosts, along with their microbial partners, may synergistically contribute to oceanic carbonate production. This discovery, if confirmed, expands the role of symbiosis in marine biomineralization and underscores its broader influence on global biogeochemical cycles.
C-C conjugated carbohydrate-porphyrin hybrid: Its therapeutic potential in photodynamic therapy and cellular uptake studies.
Chmielewska H, Baran D, Czerwińska AM … +3 more , Godlewski B, Malinowski M, Grabowska-Jadach I
J Photochem Photobiol B · 2026 Jul · PMID 42143995 · Publisher ↗
Alternative anticancer therapies are gaining momentum in modern medicinal chemistry and photodynamic therapy (PDT) is one of the most studied nowadays. In this paper we explore the biological features of unique photosens...
Alternative anticancer therapies are gaining momentum in modern medicinal chemistry and photodynamic therapy (PDT) is one of the most studied nowadays. In this paper we explore the biological features of unique photosensitiser (PS) - hydrolytically stable CC bonded glycoporphyrin (PS 1). The glycoconjugate has been obtained via modified Sonogashira reaction protocol under microwave irradiation. Glycosylation of the porphyrin system allowed to significantly reduce its dark cytotoxicity while such modification still did not hamper production of reactive oxygen species (ROS) after light irradiation. The phototherapeutic activity of PS 1 was compared with the activity of PS 2, example of unmodified synthetic porphyrin. Herein, we present chemical and biological experiments presenting effectiveness of these compounds in ROS production, cellular uptake studies, and evaluation of glycoporphyrin utility in PDT. The absence of measurable dark cytotoxicity across all examined cell lines within the tested concentration range (2.5-100 μM), combined with a clear light-induced effect, indicates a favourable selectivity profile of PS 1 at the in vitro screening stage.
Self‑oxygenating nanoparticle-mediated photodynamic therapy for biofilm control and macrophage immunomodulation in vitro.
Huang J, Chen R, Wang X … +4 more , Zhang S, Zeng Y, Chen Y, Huang X
J Photochem Photobiol B · 2026 Jul · PMID 42143994 · Publisher ↗
Periodontitis is a chronic biofilm-induced inflammatory disease that is increasingly linked to systemic conditions. Effective treatment requires removing pathogenic biofilms and modulating the host inflammatory response....
Periodontitis is a chronic biofilm-induced inflammatory disease that is increasingly linked to systemic conditions. Effective treatment requires removing pathogenic biofilms and modulating the host inflammatory response. Antibacterial photodynamic therapy (aPDT) shows promising potential in the field of antibacterial treatment. However, issues such as the hypoxic microenvironment within periodontal pockets and biofilm structures, as well as the poor stability of traditional photosensitizers, pose challenges to the efficacy of aPDT. Here, we developed a multifunctional nanoparticle MB-MnO₂@PLGA NPs (MMP NPs) by co-encapsulating methylene blue (MB) and PVA-pre-dispersed manganese dioxide (MnO₂) nanosheets into a PLGA nanocarrier using a double emulsion-solvent evaporation method. Characterization confirmed their core-shell morphology, good colloidal stability, and high MB loading. Upon 660 nm irradiation, the nanoparticles generated reactive oxygen species and catalyzed H₂O₂ to produce oxygen, relieving local hypoxia and enhancing the cell compatibility of free MB. The MMP NPs disrupted P. gingivalis and F. nucleatum biofilms and exhibited superior antibacterial activity compared to free MB. Additionally, the nanoplatform significantly downregulated IL-6 and TNF-α levels. Importantly, the nanoplatform promoted macrophage polarization toward an anti-inflammatory M2 phenotype, as indicated by increased Arg-1 and CD206 expression. This work supports a synergistic in vitro strategy that simultaneously targets infection, hypoxia, and inflammation. It holds positive significance for promoting the development of periodontal disease treatment.
Photothermal-immunotherapy enhances antitumor efficacy and modulates the tumor immune microenvironment in anaplastic thyroid carcinoma.
Yang F, Huang Y, Xu Y … +1 more , Huang D
J Photochem Photobiol B · 2026 Jul · PMID 42140067 · Publisher ↗
A combination of rapid disease progression and insufficient therapeutic options continues to complicate the clinical management of anaplastic thyroid carcinoma (ATC). The antitumor effect of photothermal therapy (PTT) ar...
A combination of rapid disease progression and insufficient therapeutic options continues to complicate the clinical management of anaplastic thyroid carcinoma (ATC). The antitumor effect of photothermal therapy (PTT) arises from heat generated in situ, leading to tumor cell damage. However, its therapeutic efficacy is constrained by insufficient tissue penetration and inadequate immune activation, making complete tumor eradication challenging. Despite its ability to induce antitumor immune responses, CpG oligodeoxynucleotide (CpG ODN)-mediated immunotherapy shows limited efficacy as a standalone approach and does not sufficiently improve the immunosuppressive conditions within the tumor microenvironment. Photothermal therapy (PTT), when used alongside CpG ODN-mediated immunotherapy, may provide enhanced antitumor effects arising from their complementary functions. In this study, we developed a nanoplatform integrating CpG ODN-mediated immune activation with the photothermal properties of Fe-doped polydopamine for the treatment of ATC. Assessment of the nanoplatform revealed satisfactory compatibility in biological contexts, accompanied by reproducible photothermal conversion performance. In vitro assessment revealed enhanced dendritic cell maturation, accompanied by an increase in pro-inflammatory cytokine production following this treatment. The combined treatment, when evaluated in vivo, was linked to decreased tumor growth and coincided with immunogenic cell death, increased dendritic cell maturation, enhanced T cell infiltration, and alterations in the immunosuppressive tumor microenvironment. Use of the combinational strategy resulted in greater antitumor effects than monotherapies, accompanied by direct tumor ablation and the activation of systemic immune responses. A therapeutic benefit for ATC may be achieved through the integration of photothermal therapy with immunotherapy.
Structural basis for hemoglobin scavenging by CD163 reveals mechanism of ligand promiscuity.
Zhou RX, Higgins MK
PLoS Biol · 2026 May · PMID 42133656 · Full text
The scavenger receptor CD163 detoxifies free hemoglobin released on erythrocyte lysis to prevent oxidative damage. The best understood route for hemoglobin detoxification involves the formation of haptoglobin-hemoglobin...
The scavenger receptor CD163 detoxifies free hemoglobin released on erythrocyte lysis to prevent oxidative damage. The best understood route for hemoglobin detoxification involves the formation of haptoglobin-hemoglobin complexes that bind CD163 and are internalized into macrophages, resulting in hemoglobin degradation. However, during conditions such as sickle cell anemia or malaria, haptoglobin is depleted. CD163 can then act as a lower-affinity receptor for free hemoglobin. Previous studies revealed that CD163 forms a multimeric "base," which presents "arms" that form a binding site for haptoglobin-hemoglobin. In this study, we use cryogenic electron microscopy to reveal how human CD163 binds hemoglobin tetramers in a process that, unlike haptoglobin-hemoglobin uptake, requires a full trimeric CD163 assembly to achieve sufficient binding. We reveal how flexibility at the calcium-mediated base, combined with a hinge between receptor domains 2 and 3, allows the arms to wrap around diverse ligands. This brings together multiple small binding surfaces from different domains to form cradles for different ligands. These adaptations allow the scavenger receptor to be promiscuous, protecting us from oxidative damage caused by hemoglobin release in various pathological conditions.
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