J Cyst Fibros. 2025 May 31:S1569-1993(25)01497-3. doi: 10.1016/j.jcf.2025.05.008. Online ahead of print.

ABSTRACT

The use of bacteriophage (phage) to treat bacterial infection of airways in persons with cystic fibrosis (CF) is gaining interest. However, phenotypic diversification of bacteria during chronic airway infection presents a potential challenge to this therapy. We recovered and subcultured two or three Burkholderia colonies from each of 12 CF sputum samples. All isolates were tested for their susceptibility to a panel of 65 Burkholderia-targeting phages. We observed that 9 (75%) of the 12 colony sets comprised mixtures of isolates that were sensitive or resistant to one or more of the phages tested. The occurrence of mixed populations of phage-sensitive and phage-resistant Burkholderia in individuals with CF needs to be considered in the development of phage therapy for this patient population.

PMID:40451706 | DOI:10.1016/j.jcf.2025.05.008

Am J Transplant. 2025 May 29:S1600-6135(25)00286-2. doi: 10.1016/j.ajt.2025.05.029. Online ahead of print.

ABSTRACT

Acute cellular rejection (ACR) is a key contributor to chronic lung allograft dysfunction (CLAD) following transplantation; while treatable, traditional immunosuppressive (IS) therapies are associated with significant side effects. Gene therapy offers an approach to modulate recipient immune responses while minimizing the toxicity of conventional IS. In this study, we evaluated AAV-mediated PD-L1 overexpression, an inhibitory ligand of T cells, in a rat single lung transplant model. Allogeneic Brown Norway lungs were transplanted into Fischer F344 recipients and assigned to three groups: (1) AAV9-PD-L1 via the bronchus during static cold storage, (2) no virus control, or (3) AAV9-luciferase control. All animals received CTLA-4 immunoglobulin on postoperative day (POD) 1, and sacrificed on POD14. Rejection was evaluated by a blinded lung transplant pathologist, and PD-L1 expression and CD8+ T-cell infiltration assessed via immunohistochemistry. By POD14, the AAV9-PD-L1 group displayed significantly reduced rejection severity (mean score 1.40) compared to controls (mean 3.60; p=0.005). The AAV9-luciferase group exhibited comparable rejection scores to no-virus controls (mean 3.5). Immunohistochemistry confirmed exogenous PD-L1 expression, however no significant difference in CD8+ T-cell count was observed between groups. These findings demonstrate that AAV PD-L1 gene delivery can attenuate ACR in lung transplants, offering a potential strategy to improve outcomes.

PMID:40449603 | DOI:10.1016/j.ajt.2025.05.029

Lancet Respir Med. 2025 May 28:S2213-2600(25)00159-6. doi: 10.1016/S2213-2600(25)00159-6. Online ahead of print.

NO ABSTRACT

PMID:40449514 | DOI:10.1016/S2213-2600(25)00159-6

Soc Sci Med. 2025 May 15;380:118175. doi: 10.1016/j.socscimed.2025.118175. Online ahead of print.

ABSTRACT

Individuals living with rare diseases have conventionally been understood as being particularly vulnerable, which often promotes a negative and stigmatising interpretation of vulnerability. In this article, we embrace the framework of structural (health) vulnerability to gain a deeper understanding of the circumstances and factors contributing to adverse outcomes in the specific context of a Global South country, India, and a particular rare disease, Cystic Fibrosis (CF). By drawing on published materials and preliminary data from an evolving ethnographic research project, we contend that it is crucial to examine global power dynamics and the unequal distribution of resources to contextualize the precarious conditions experienced by Indians living with CF. Epistemologically, this stems from pervasive racialised assumptions ingrained in CF knowledge production, constituting a form of hermeneutic injustice, while economically, India's position in the global bioeconomy restricts access to potentially beneficial treatments derived from advanced clinical research. Moreover, reduced investment in healthcare by the Indian Central Government, notably evident in its rare disease policy, leaves CF patients reliant on philanthropy, which is susceptible to shifting interests and priorities. Therefore, we argue that focusing on structural (health) vulnerability is essential for shedding light on the distinct challenges faced by individuals living with CF in India, as well as in other locations in the Global South.

PMID:40449408 | DOI:10.1016/j.socscimed.2025.118175

Patient Educ Couns. 2025 May 21;138:109183. doi: 10.1016/j.pec.2025.109183. Online ahead of print.

ABSTRACT

OBJECTIVES: We explored the impact of taking part in a medication discontinuation study for people with cystic fibrosis (CF) on subsequent clinical conversations and what interviewees valued as characteristics of these conversations.

METHODS: This analysis is part of the Qualitative Understanding of the Experience of SIMPLIFY Trial (QUEST), a qualitative companion study to a discontinuation trial of two commonly prescribed medications for people with CF. We interviewed 109 total individuals (87 people with CF and 22 caregivers). The interviews were analyzed to explore the influence of participation in a discontinuation study on clinical conversations.

RESULTS: Respect emerged as an overarching theme of these interviews: how much the interviewees respected their clinicians and how they appreciated having their autonomy respected too. Other desirable attributes of clinical conversations surfaced including the importance of reciprocity, empowerment, sensitivity, partnership, empathy, consideration and transparency; (R.E.S.P.E.C.T).

CONCLUSIONS: Communication is a fundamental aspect of chronic disease management. This population study focused on patient perspectives of clinical conversations after sharing the experience of being in a novel discontinuation study. Since the acronym R.E.S.P.E.C.T. emerged from the data, we believe it has value as a framework for clinical conversations with people who have chronic conditions that require active selfmanagement.

PMID:40449206 | DOI:10.1016/j.pec.2025.109183

FEBS Lett. 2025 May 31. doi: 10.1002/1873-3468.70083. Online ahead of print.

ABSTRACT

Cryo-electron microscopy has yielded high-resolution structural data of the multidrug efflux transporter P-glycoprotein (ABCB1), but its direct and indirect interactions within the native membrane environment have remained largely unexplored. Here, we compared the fluidity gradients of plasma membranes of the drug-sensitive CHO cell line AuxB1 and its P-glycoprotein overexpressing derivative B30 by fluorescence anisotropy of embedded n-(9-anthroyloxy) fatty acid probes (n = 2, 7, 9, 12, 16) in the temperature range of 10-50 °C. The shape of the temperature profiles of probe mobility was comparable in AuxB1 and B30 membranes, but did not match. Overexpression of P-glycoprotein smoothened the transversal gradient of the out-of-plane mode of rotation of the probes, which may facilitate the partitioning of hydrophobic drugs into the membrane and thereby increase the speed of P-glycoprotein to pump the drug out of the cell.

PMID:40448544 | DOI:10.1002/1873-3468.70083

J Diabetes Sci Technol. 2025 May 30:19322968251333441. doi: 10.1177/19322968251333441. Online ahead of print.

ABSTRACT

This consensus report evaluates the potential role of continuous glucose monitoring (CGM) in screening for stage 2 type 1 diabetes (T1D). CGM offers a minimally invasive alternative to venous blood testing for detecting dysglycemia, facilitating early identification of at-risk individuals for confirmatory blood testing. A panel of experts reviewed current evidence and addressed key questions regarding CGM's diagnostic accuracy and screening protocols. They concluded that while CGM cannot yet replace blood-based diagnostics, it holds promise as a screening tool that could lead to earlier, more effective intervention. Metrics such as time above range >140 mg/dL could indicate progression risk, and artificial intelligence (AI)-based modeling may enhance predictive capabilities. Further research is needed to establish CGM-based diagnostic criteria and refine screening strategies to improve T1D detection and intervention.

PMID:40444471 | PMC:PMC12125016 | DOI:10.1177/19322968251333441

NPJ Antimicrob Resist. 2025 May 30;3(1):46. doi: 10.1038/s44259-025-00115-1.

ABSTRACT

The lack of novel antimicrobial compounds in the development pipeline cries for innovative approaches regarding their discovery. In this Perspective, we discuss how microbial interactions play a significant role in shifting a pathogen's response to antibacterial treatment and negatively impact patient outcomes. Furthermore, we argue that interspecies interactions are often overlooked in treatment selection and current drug screening approaches, and modeling disease-relevant polymicrobial communities could help in unraveling novel strategies to eradicate pathogens.

PMID:40447766 | DOI:10.1038/s44259-025-00115-1

Thorax. 2025 May 30:thorax-2024-222242. doi: 10.1136/thorax-2024-222242. Online ahead of print.

ABSTRACT

BACKGROUND: Despite significant clinical improvements, there is evidence of persisting airway inflammation in people with cystic fibrosis (CF) established on elexacaftor/tezacaftor/ivacaftor (ETI) therapy. As CF is a multi-system disease, systemic immune profiles can reflect local inflammation within the lungs and other organs. Understanding systemic inflammation after ETI therapy may reveal important translational insights. This study aims to profile systemic inflammatory changes and relate these to the well-documented improvements observed with ETI therapy.

METHODS: We conducted a single-centre longitudinal study with 57 CF subjects initiating ETI therapy. All participants were Phe508del homozygous or Phe508del/minimal function. Blood samples were collected pre-ETI and 3-12 months post-therapy initiation. Analyses included mass spectrometry-based proteomics, a multiplex immunoassay, and flow cytometry for peripheral immune cell counts and phenotype. Controls samples were provided by 29 age-matched healthy controls.

RESULTS: Systemic inflammation reduced with ETI therapy; however, the immune profile remained distinct from healthy controls. ETI reduced neutrophil counts and was associated with a more mature, less inflammatory phenotype, as well as a shift towards an immune resolving state associated with increased CD206 expression. Cytokines known to influence neutrophil levels reduced with therapy. Despite ETI therapy, neutrophil and monocyte counts remained elevated compared with healthy controls. There was no obvious association between the ETI-related improvements in systemic inflammation and lung function.

CONCLUSIONS: Patients with CF showed evidence of persisting systemic inflammation despite ETI therapy, which may have long-term potentially adverse effects on respiratory and other organ systems.

PMID:40447326 | DOI:10.1136/thorax-2024-222242

Int J Biol Macromol. 2025 May 28:144741. doi: 10.1016/j.ijbiomac.2025.144741. Online ahead of print.

ABSTRACT

Polymeric hydrogels are paramount to outstanding applications in biology, medicine, pharmacy. Their similarity to living tissues is leveraged in clinical branches (oncology, cardiology, immunology, neurology, wound healing) for delivering a large range of drugs (encompassing DNA, RNA, protein molecules) and realizing in-vivo models of stimuli-responsive or controlled drug release. Rubber elasticity theory and the swollen network hypothesis are key for properly designing the geometric and mechanical features of hydrogels and polymer networks. The assumption of a Gaussian distribution of end-to-end lengths in a polymer molecule, however, can break down in several cases. Here, strongly supported by Low field NMR and rheology experiments, we propound the generalized Weibull law of extreme value statistics (EVS) to have universal validity in hydrogel materials. Mesh size values that account for an intrinsic statistical dependence between monomeric positions (or stiffness) show much better agreement with measurements conducted on physically crosslinked samples (agar, alginate and scleroglucan), including sputum specimens (rich in mucins) from patients affected by chronic respiratory conditions (cystic fibrosis) and on chemically crosslinked samples (poly-vinylpyrrolidone, PVP; poly-(ethylene-glycol/propylene-glycol), PEG/PPG). Across all ten gels, the Gaussian distribution yields the smallest average mesh size, ranging roughly from 7 nm for the densest alginate 2 % (9 gl-1) hydrogel to about 80 nm for one of the sputum. Working with the pierced Gaussian inflates the mesh size to ≈1.5 × the Gaussian value, with increases from a modest +4 % in alginate 1 % up to nearly +100 % in the open PVP network (48 → 98 nm). The generalized Weibull distribution usually falls between the two Gaussians, yet in agar 1 % and scleroglucan 2 % it overtakes the pierced Gaussian (e.g. 20.2 > 15.8 nm for agar 1 %), reflecting a strong heavy-tailed distribution. The predicted mesh order therefore is Gaussian < generalized Weibull ≈ pierced Gaussian, with the precise ranking ruled by the width and skewness of each network statistics. Overall, our findings - being straightforward to apply - will profoundly impact on the description, conception and control of polymer networks, which often demand advanced instrumental techniques for compensating the lack of adequate predictive models. Among other relevant implications, aside from drug delivery, we highlight the characterization of the photothermal (or thermoplasmonic) response of hydrogel matrices hosting metal nanoparticles (e.g. with applications in hyperthermia cancer treatment and enhanced chemical processes). On the theoretical side, we emphasize the study of transport and thermomechanical properties of polymeric networks.

PMID:40446991 | DOI:10.1016/j.ijbiomac.2025.144741

PLoS Pathog. 2025 May 30;21(5):e1013190. doi: 10.1371/journal.ppat.1013190. Online ahead of print.

ABSTRACT

Mycobacterium abscessus (MAB) is a clinically significant multidrug-resistant (MDR) pathogen, particularly implicated in pulmonary infections among cystic fibrosis (CF) patients. Tedizolid (TZD), an oxazolidinone-class antibacterial drug, has been recommended as an alternative treatment for MAB-infected patients who are intolerant to or whose isolate is resistant to first-line drugs including linezolid (LZD). To investigate the TZD resistance mechanisms in MAB, we isolated 23 TZD-resistant MAB mutants and performed whole-genome sequencing (WGS) to identify resistance-associated genes. Frequent mutations were identified in MAB_2885, encoding a putative TetR transcriptional regulator, and MAB_2303, encoding a putative mycobacterial membrane protein large (MmpL). Drug susceptibility testing confirmed that MAB_2885 mutations contribute to both TZD and LZD resistance in MAB. RNA-seq analysis revealed that restoring wild-type MAB_2885 in mutants downregulated the MAB_2302-MAB_2303. Electrophoretic mobility shift assay (EMSA) showed the MAB_2885 protein binds to its target sequence upstream of MAB_2302-MAB_2303, further confirming their regulatory relationship. The W91R mutation in the MAB_2885 protein was found to impair its DNA-binding activity compared to the wild-type. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis confirmed that MAB_2302-MAB_2303 functions as a TZD efflux pump. Additionally, overexpression of MAB_2885 in M. abscessus subsp. bolletii and M. abscessus subsp. massiliense also increased their TZD susceptibility and downregulated their respective MmpS-MmpL orthologs. Overall, our study demonstrates that mutations in MAB_ 2885 contribute to TZD and LZD resistance by disrupting the negative regulation of the downstream MAB_2302-MAB_2303, which functions as a direct efflux pump for TZD. These findings provide new insights into oxazolidinone resistance mechanisms in MAB and identify potential biomarkers for detecting drug resistance.

PMID:40445981 | DOI:10.1371/journal.ppat.1013190

Nanomedicine (Lond). 2025 May 30:1-17. doi: 10.1080/17435889.2025.2509477. Online ahead of print.

ABSTRACT

Messenger RNA (mRNA)-based therapeutics offer the potential to treat a variety of pulmonary disorders that arise due to genetics, infectious diseases, and chronic respiratory conditions. However, various physiological barriers in the lungs, such as mucociliary clearance, macrophage phagocytosis, and lung surfactant interference, present challenges for efficient mRNA delivery. Polymeric nanoparticles (NPs) have emerged as a therapeutic platform for delivering mRNA therapeutics due to their stability, tunability, and controlled release properties, making them suitable and potentially ideal for encapsulating and protecting mRNA molecules for delivery in vivo. Continued advances in polymer and NP design have improved mucus penetration and cellular uptake upon lung delivery; further, administration via local and systemic routes enable modulation of NP biodistribution. These advancements benefit the potential treatment of a range of pulmonary diseases, including viral infections, cystic fibrosis (CF), asthma, and lung cancer, by facilitating immune modulation and genetic therapy delivery. In this review, we explore how polymeric NPs address disease-specific requirements and physiological challenges to expand the potential for therapeutic mRNAs in the lung.

PMID:40445199 | DOI:10.1080/17435889.2025.2509477

J Investig Med. 2025 May 30:10815589251348918. doi: 10.1177/10815589251348918. Online ahead of print.

ABSTRACT

Bacterial extracellular vesicles (EVs) are important mediators of host infection. Persons with cystic fibrosis (CF) often suffer from chronic infection with Pseudomonas aeruginosa, an opportunistic pathogen. However, the relative abundance of P. aeruginosa is not associated with the onset of increased pulmonary symptoms, known as a pulmonary exacerbation. We hypothesized that the cargo of P. aeruginosa EVs is different at times of baseline wellness and pulmonary exacerbation onset in persons with CF. This is the first study to characterize and compare P. aeruginosa EVs at these two time points, using a novel series of steps to isolate the P. aeruginosa EVs directly from the sputum of persons with CF. Our study found a differential packaging of P. aeruginosa proteins at baseline wellness and pulmonary exacerbation, with six proteins being more frequently present in pulmonary exacerbation samples. Additionally, we were able to demonstrate the P. aeruginosa EVs isolated from the sputum of persons with CF at the time of pulmonary exacerbation induced an inflammatory response in CF human bronchial epithelial (HBE) cells. These data, while preliminary, support the clinical relevance of P. aeruginosa EVs in influencing gene regulation and lung inflammation and immunity in persons with CF.

PMID:40444885 | DOI:10.1177/10815589251348918

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2025 Jun;39(6):590-596. doi: 10.13201/j.issn.2096-7993.2025.06.017.

ABSTRACT

One of the main pathological features of airway inflammatory diseases is hypersecretion of airway mucus, which is manifested by goblet cell hyperplasia and mucociliary clearance dysfunction. In recent years, it has been found that the molecular structure of calcium activated chloride ion channels, transmenbrane protein 16A（TMEM16A）, is closely related to airway mucus hypersecretion.TMEM16A not only mediates ion transepithelial transport and hydration, but also participates in the regulation of mucin secretion. TMEM16A is highly expressed in airway epithelium of a variety of inflammatory diseases of upper and lower airway, such as asthma, cystic fibrosis, allergic rhinitis, chronic sinusitis and so on. Understanding the expression level and regulation mechanism of TMEM16A in different airway diseases and revealing its physiological function and pathological mechanism is critical for targeted disease treatment. This paper summarizes the research status of the discovery process, structural characteristics and regulatory mechanism of TMEM16A, and then summarizes the expression level of TMEM16A in asthma, cystic fibrosis, allergic rhinitis and chronic sinusitis ant related pathological mechanisms, clarifies the potential value of TMEM16A as a therapeutic target for the above four diseases, in order to guide treatment of airway inflammatory diseases.

PMID:40443386 | DOI:10.13201/j.issn.2096-7993.2025.06.017

Nat Rev Microbiol. 2025 May 29. doi: 10.1038/s41579-025-01193-8. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa has long served as a model organism in microbiology, particularly for studies on gene expression, quorum sensing, antibiotic resistance, virulence and biofilm formation. Its genetic tractability has advanced the understanding of complex regulatory networks and experimental evolution. The versatility of this bacterium stems from its genomic variability, metabolic flexibility and phenotypic diversity, enabling it to thrive in diverse environments, both as a harmless saprophyte and an opportunistic human pathogen. P. aeruginosa can cause acute and chronic human infections, particularly in patients with underlying immune deficiencies. Its intrinsic antibiotic tolerance and resistance, together with its ability to produce multiple virulence factors while rapidly adapting to infection conditions, pose a major clinical challenge. In this Review, we explore key features contributing to the ecological and pathogenic versatility of P. aeruginosa. We examine the molecular mechanisms and ecological and evolutionary implications of quorum sensing and biofilm formation. We explore the virulence strategies and in vivo fitness determinants, as well as the evolutionary dynamics and global epidemiology of P. aeruginosa, with a focus on antimicrobial resistance. Finally, we discuss emerging strategies to control P. aeruginosa infections and address outstanding questions in the field.

PMID:40442328 | DOI:10.1038/s41579-025-01193-8

Clin Exp Allergy. 2025 May 29. doi: 10.1111/cea.70089. Online ahead of print.

ABSTRACT

BACKGROUND: Gaining a better understanding of the risk factors for severe anaphylaxis represents a crucial challenge for physicians. This survey aimed to analyse cases of severe food anaphylaxis and assess potential risk factors for severity.

METHODS: We retrospectively analysed food anaphylaxis cases recorded by the French-speaking Allergy-Vigilance Network (2002-2021) and compared the main characteristics of grade 3 (Ring classification) and grade 4 cases using univariate and multivariate statistical analyses.

RESULTS: Of the 2621 food anaphylaxis cases reported, 731 (27.9%) were considered severe (grade 3, n = 687 [94%] and grade 4, n = 44 [6%]; 19 deaths). Overall, 56.1% of cases were adults (mean age: 28.3 years) and 53.7% were male. The most frequent triggers were peanut (13.9%), wheat (9.4%), cashew (5.8%), shrimp (5.3%), and cow's milk (4.6%). More grade 4 anaphylaxis cases occurred in children than in adults (26 vs. 18; p = 0.01). In univariate analysis, individuals with grade 4 anaphylaxis were more likely to have a history of allergy to the culprit food (71.1% vs. 42.1%; p < 0.001), asthma diagnosis (59.5% vs. 30.4%; p < 0.001), and peanut as the culprit food (34.1% vs. 12.6%; p < 0.001). In multivariate analysis, factors predictive of grade 4 anaphylaxis were asthma diagnosis (OR [95% CI]: 3.41 [1.56-7.44]; p = 0.002) and peanut as the culprit trigger (OR [95% CI]: 3.46 [1.28-9.34]; p = 0.014).

CONCLUSIONS: Our data highlight the risk factors for severe food anaphylaxis, notably a history of asthma and peanut as the culprit food. These individuals should benefit from personalised management strategies.

PMID:40441889 | DOI:10.1111/cea.70089

Res Vet Sci. 2025 May 26;192:105720. doi: 10.1016/j.rvsc.2025.105720. Online ahead of print.

ABSTRACT

Several bacteria associated with chronic lung pathology use quorum sensing (QS) signaling molecules to regulate their virulence in pure cultures and poly-microbial communities. Their excessive growth and biofilm formation in the respiratory tract increase the morbidity and mortality of inflammatory airway diseases in humans, such as chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF). In horses, severe equine asthma (SEA) has many parallels to these human diseases. We hypothesized that QS molecules associated with the most common biofilm-forming lung pathogens in humans (Pseudomonas aeruginosa, Stenotrophomonas maltophilia) may also be present in the lungs of horses with SEA. Samples of bronchoalveolar lavage fluid (BALf) were taken from twenty horses with exacerbated SEA. Microbiological cultures of the BALf samples were performed. Liquid chromatography coupled with tandem mass spectrometry was used to identify C4-HSL, C6-HSL, 3-oxo-C12-HSL and 11-methyl-2-dodecenoic acid, which are associated with the QS mechanisms of Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Stenotrophomonas maltophilia was identified in three horses. Pseudomonas aeruginosa was not identified in any sample. The quorum sensing molecules C4-HSL, C6-HSL, 3-oxo-C12-HSL associated with biofilm formation by P. aeruginosa and 11-methyl-2-dodecenoic acid associated with biofilm formation by S. maltophila were not detected. It is unlikely that biofilm-forming bacterial strains associated with chronic lung disease in humans express similar virulence in SEA.

PMID:40441075 | DOI:10.1016/j.rvsc.2025.105720

RSC Med Chem. 2025 May 27. doi: 10.1039/d5md00203f. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a life-limiting genetic disease that affects multiple organ systems. It is caused by a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which results in the absence or damage of a relevant protein. If left untreated, it causes death in early childhood. The advent of more efficacious treatments has resulted in a notable increase in the life expectancy of CF patients. This has, in turn, led to an elevated risk of developing specific types of cancer. This review commences with an examination of CF from the standpoint of its etiology and therapeutic modalities. Subsequently, it presents a list of epidemiological studies that suggest an altered predisposition to certain cancers. A heightened risk is well documented, particularly in relation to the gastrointestinal tract. The following section addresses the role of CFTR in view of its potential involvement in the progression of various types of cancer. Several studies have indicated that the levels of the CFTR protein are reduced in many tumors and that this reduction is associated with the progression of the tumors. These decreased expressions are known to occur in the gastrointestinal tract, lungs, bladder, and/or prostate cancer. Conversely, ovarian, stomach, and cervical cancer are connected with its higher expression. The final section of the review focuses on the molecular mechanism of action of the CFTR protein in signaling pathways that affect cell proliferation and the process of carcinogenesis. This section attempts to explain the increased predisposition to cancer observed in patients with CF.

PMID:40438286 | PMC:PMC12107394 | DOI:10.1039/d5md00203f

Chem Sci. 2025 May 9. doi: 10.1039/d5sc02049b. Online ahead of print.

ABSTRACT

Burkholderia cepacia complex (Bcc) is a group of Gram-negative opportunistic pathogens highly responsible for chronic pulmonary infection in cystic fibrosis (CF). Current therapies involving double or triple antibiotic combinations can rarely eradicate the pathogen in chronically infected patients owing to its intrinsic resistance to a variety of antibiotics. Herein, we show that a bismuth drug (and related compounds) could inhibit the growth of clinically antibiotic-resistant Bcc strains, with MIC (ca. 25 μg mL-1) comparable to that for Helicobacter pylori, and the combination of a bismuth drug and antibiotics also demonstrated excellent activity against biofilm and persisters of Bcc. Importantly, the in vitro antimicrobial activity of a bismuth drug could be well translated into in vivo evidenced by about 50% survival rates in the Galleria mellonella infection model. Transcriptomics analysis shows the dynamic responses of Bcc to bismuth treatment. Using a homemade metalloproteomic approach, we could identify 26 BiIII-binding proteins (15 cytosolic proteins and 11 membrane proteins). Further mechanistic studies reveal that bismuth drugs initially target the TCA cycle through the binding and inactivation of a series of enzymes including malate dehydrogenase (MDH), malate synthase (AceB), and succinyl coenzyme A synthetase (SCS), then interfere oxidative phosphorylation through binding to terminal oxidases, i.e., CyoC and CydA, to disrupt electron transport chain, eventually, disrupt protein translation and ribosome via binding and down-regulation of key proteins. Our studies highlight the great potential of bismuth drugs and/or compounds to treat multidrug-resistant Bcc infections.

PMID:40438165 | PMC:PMC12107623 | DOI:10.1039/d5sc02049b

Oncoimmunology. 2025 Dec;14(1):2512109. doi: 10.1080/2162402X.2025.2512109. Epub 2025 May 28.

ABSTRACT

Nonmutated mitochondrial DNA (mtDNA) from T lymphocytes can be incorporated into cancer cells bearing mutated mtDNA to repair their bioenergetic deficiency. However, a recent paper by Ikeda et al. indicates that mutated mtDNA from malignant cells can also be transferred into tumor-infiltrating T lymphocytes to subvert their function in cancer immunosurveillance.

PMID:40434021 | PMC:PMC12123971 | DOI:10.1080/2162402X.2025.2512109