Molecular cloning, expression, and functional analysis of a putative lectin from the pearl oyster (Pinctada fucata, Gould 1850).

Marine lectins are a group of proteins that possess specific carbohydrate recognition and binding domains. They exhibit various activities, including antimicrobial, antitumor, antiviral, and immunomodulatory effects. In this study, a novel galectin-binding lectin gene named PFL-96 (GenBank: OQ561753.1) was cloned from Pinctada fucata. The PFL-96 gene has an open reading frame of 324 base pairs (bp) and encodes a protein comprising 107 amino acids. The protein has a molecular weight of 11.95 kDa and an isoelectric point of 9.27. It contains an N-terminal signal peptide and a galactose-binding lectin domain. The sequence identity to lectin proteins from fish, echinoderms, coelenterates, and shellfish ranges from 31.90 to 40.00 %. In the phylogenetic analysis, it was found that the PFL-96 protein is closely related to the lectin from Pteria penguin. The PFL-96 recombinant protein exhibited coagulation activity on 2 % rabbit red blood cells at a concentration of ≥8 µg/mL. Additionally, it showed significant hemolytic activity at a concentration of ≥32 µg/mL. The PFL-96 recombinant protein exhibited significant antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Candida albicans, and Vibrio alginolyticus, with minimum inhibitory concentrations (MIC) of 4, 8, 16, and 16 µg/mL, respectively. The minimum bactericidal concentrations (MBC) were determined to be 8, 16, 32, and 32 µg/mL, respectively. Furthermore, the PFL-96 recombinant protein exhibited inhibitory effects on the proliferation of Hela tumor cells, HepG2 tumor cells, and C666-1 tumor cells, with IC50 values of 7.962, 8.007, and 9.502 µg/mL, respectively. These findings suggest that the recombinant protein PFL-96 exhibits significant bioactivity in vitro, contributing to a better understanding of the active compounds found in P. fucata. The present study establishes a fundamental basis for further investigation into the mechanism of action and structural optimization of the recombinant protein PFL-96. The aim is to develop potential candidates for antibacterial and anti-tumor agents.

Regulation of bla system in ST59-related oxacillin-susceptible mecA-positive Staphylococcus aureus.

OBJECTIVES: Oxacillin-susceptible mecA-positive Staphylococcus aureus (OS-MRSA) is clinically significant and isolated globally but the mechanism of its occurrence remains indistinct. We sought to assess the mechanism of regulating oxacillin susceptibility in OS-MRSA isolates by evaluating the evolutionary dynamics of OS-MRSA and the discrepancies of mecA-regulating genes in OS-MRSA and oxacillin-resistant MRSA (OR-MRSA). METHODS: Nine OS-MRSA isolates and 77 OR-MRSA isolates were sequenced using next-generation sequencing (NGS) platforms. Two representative OS-MRSA isolates (ET-13, ET-16) were induced to be oxacillin resistant and sequenced also. OS-MRSA ET-16 and its counterpart isolate with induced oxacillin resistance, ET-16I, and their mutants were used to confirm the role of the bla system in regulating methicillin susceptibility. Oxacillin MICs were determined using Etests. Expression of mecA and blaR1 was quantified by quantitative RT-PCR. RESULTS: A deletion in blaR1 in most OS-MRSA isolates (7/9; 77.78%) was found using NGS data, and overexpression of OR-blaR1 in OS-MRSA isolate ET-16 restored its oxacillin resistance. OS-MRSA could be induced to be oxacillin resistant, while growth was suppressed in the induced isolates. Plasmid containing the bla locus was lost in most induced isolates during the induction process and complementation of blaR1-blaI from OS-MRSA ET-16 to the induced isolate ET-16I converted its oxacillin susceptibility. CONCLUSIONS: Deletion in blaR1 resulted in oxacillin susceptibility in OS-MRSA, and loss of the bla regulator in OS-MRSA restored oxacillin resistance. The bla system played a crucial role in regulating oxacillin susceptibility in OS-MRSA isolates.

Contribution of Staphylococcal Enterotoxin B to Staphylococcus aureus Systemic Infection.

Staphylococcal enterotoxin B (SEB), which is produced by the major human pathogen, Staphylococcus aureus, represents a powerful superantigenic toxin and is considered a bioweapon. However, the contribution of SEB to S. aureus pathogenesis has never been directly demonstrated with genetically defined mutants in clinically relevant strains. Many isolates of the predominant Asian community-associated methicillin-resistant S. aureus lineage sequence type (ST) 59 harbor seb, implying a significant role of SEB in the observed hypervirulence of this lineage. We created an isogenic seb mutant in a representative ST59 isolate and assessed its virulence potential in mouse infection models. We detected a significant contribution of seb to systemic ST59 infection that was associated with a cytokine storm. Our results directly demonstrate that seb contributes to S. aureus pathogenesis, suggesting the value of including SEB as a target in multipronged antistaphylococcal drug development strategies. Furthermore, they indicate that seb contributes to fatal exacerbation of community-associated methicillin-resistant S. aureus infection.

Roles of the Site 2 Protease Eep in Staphylococcus aureus.

In Enterococcus faecalis, the site 2 protease Eep generates sex pheromones, including cAM373. Intriguingly, in Staphylococcus aureus, a peptide similar to cAM373, named cAM373_SA, is produced from the camS gene. Here, we report that the staphylococcal Eep homolog is not only responsible for the production of cAM373_SA but also critical for staphylococcal virulence. As with other Eep proteins, the staphylococcal Eep protein has four transmembrane (TM) domains, with the predicted zinc metalloprotease active site (HEXXH) in the first TM domain. eep deletion reduced the cAM373_SA activity in the culture supernatant to the level of the camS deletion mutant. It also markedly decreased the cAM373 peptide peak in a high-performance liquid chromatography (HPLC) analysis. Proteomics analysis showed that Eep affects the production and/or the release of diverse proteins, including the signal peptidase subunit SpsB and the surface proteins SpA, SasG, and FnbA. eep deletion decreased the adherence of S. aureus to host epithelial cells; however, the adherence of the eep mutant was increased by overexpression of the surface proteins SpA, SasG, and FnbA. eep deletion reduced staphylococcal resistance to killing by human neutrophils as well as survival in a murine model of blood infection. The overexpression of the surface protein SpA in the eep mutant increased bacterial survival in the liver. Our study illustrates that in S. aureus, Eep not only generates cAM373_SA but also contributes to the survival of the bacterial pathogen in the host.IMPORTANCE The emergence of multidrug-resistant Staphylococcus aureus makes the treatment of staphylococcal infections much more difficult. S. aureus can acquire a drug resistance gene from other bacteria, such as Enterococcus faecalis Intriguingly, S. aureus produces a sex pheromone for the E. faecalis plasmid pAM373, raising the possibility that S. aureus actively promotes plasmid conjugation from E. faecalis In this study, we found that the staphylococcal Eep protein is responsible for sex pheromone processing and contributes to the survival of the bacteria in the host. These results will enhance future research on the drug resistance acquisition of S. aureus and can lead to the development of novel antivirulence drugs.

Magnetic targeting enhances the cutaneous wound healing effects of human mesenchymal stem cell-derived iron oxide exosomes.

Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

Rhein exhibits antioxidative effects similar to Rhubarb in a rat model of traumatic brain injury.

BACKGROUND: The brain is secondarily harmed by pathological, physiological, and biological reactions that are caused by traumatic brain injury (TBI). Rhein, a significant composition of Rhubarb, is a well-known traditional Chinese treatment method and has a strong oxidation-resisting characteristic, but Rhein's mechanism remains unclear. METHODS: This study aimed to identify Rhein in the brain tissues of TBI model of rats, and confirm whether Rhein induced an antioxidative effect similar to its parent medicine, Rhubarb. First, the ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was applied to identify Rhein in the brain tissue of the controlled cortical impact (CCI) rats after intra-gastric administration of Rhubarb. Further, for the purpose of calculating the oxidant stress of the CCI rats, the malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione disulfide (GSSG), as well as the proportion of glutathione (GSH)/GSSG were measured in the brain tissues. RESULTS: The results showed that Rhein was absorbed in the brain tissues of CCI rats. Rhubarb and rhein elevated the SOD, CAT activities, GSH level, and GSH/GSSG ratio, and diminished the MDA and GSSG levels. CONCLUSION: The data demonstrated that Rhubarb and Rhein had the potential to be used as a neuroprotective drug for TBI, and that Rhein induced an antioxidative effect similar to its parent medicine, Rhubarb.

A method for amplification of unknown flanking sequences based on touchdown PCR and suppression-PCR.

Thermal asymmetric staggered PCR is the most widely used technique to obtain the flanking sequences. However, it has some limitations, including a low rate of positivity, and complex operation. In this study, a improved method of it was made based on suppression-PCR and touchdown PCR. The PCR fragment obtained by the amplification was used directly for sequencing after gel purification. Using this improved method, the positive rate of amplified flanking sequences of the ATMT mutants reached 99%. In addition, the time from DNA extraction to flanking sequence analysis was shortened to 2 days with about 6 dollars each sample.

An ultra high performance liquid chromatography with tandem mass spectrometry method for plasma and cerebrospinal fluid pharmacokinetics of rhein in patients with traumatic brain injury after administration of rhubarb decoction.

Damage of blood-brain barrier is a common result of traumatic brain injury. This damage can open the blood-brain barrier and allow drug passage. An ultraperformance liquid chromatography with tandem mass spectrometry method was established to determine the concentration of rhein in the biofluids (plasma and cerebrospinal fluid) of patients with a compromised blood-brain barrier following traumatic brain injury after rhubarb administration. Furthermore, the pharmacokinetic profiles were analyzed. A triple-quadruple tandem mass spectrometer with electrospray ionization was used for rhein detection. The mass transition followed was m/z 283.06→239.0. The calibration curve was linear in the concentration range of 10-8000 ng/mL for the biofluids. The intra- and interday precisions were less than 10%. The relative standard deviation of recovery was less than 15% in biological matrices. The pharmacokinetic data showed that rhein was rapidly transported into biofluids, and exhibited a peak concentration 1 h after rhubarb administration. The elimination rate of rhein was slow. The AUCcerebrospinal fluid /AUCplasma (AUC is area under curve) of rhein was approximately 17%, indicating that portions of rhein could pass the impaired blood-brain barrier. The method was successfully applied to quantify rhein in the biofluids of all patients. The data presented can help to guide clinical applications of rhubarb for treating traumatic brain injury.

Determination of hydroxysafflor yellow A in biological fluids of patients with traumatic brain injury by UPLC-ESI-MS/MS after injection of Xuebijing.

A simple, novel, specific, rapid and reproducible ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry method has been developed and validated for the determination of hydroxysafflor yellow A (HSYA) in biological fluids (plasma, urine and cerebrospinal fluid) of patients with traumatic brain injury after intravenous injection of Xuebijing (XBJ). Liquid-liquid extraction was performed, and separation was carried out on an Acquity UPLC™ BEH C18 column, with gradient elution using a mobile phase composed of methanol and 0.1% formic acid at a flow rate of 0.3 mL/min. A triple quadrupole tandem mass spectrometer with electrospray ionization was used for the detection of HSYA. The mass transition followed was m/z 611.0 → 491. The retention time was less than 3.0 min. The calibration curve was linear in the concentration range from 2 to 6125 ng/mL for cerebrospinal fluid, plasma and urine. The intra- and inter-day precisions were <10%, and the relative standard deviation of recovery was <15% for HSYA in biological matrices. The method was successfully applied for the first time to quantify HSYA in the biological fluids (especially in cerebrospinal fluid) of patients with traumatic brain injury following intravenous administration of XBJ.

Rapid Separation and API Grades Identification of Base Oil in Low Viscosity Gasoline Engine Oil SN 0W-16.

Using low viscosity engine oil is one of the most economical and easily achievable ways to improve fuel economy. Base oil is a main component in low viscosity engine oils, and therefore, the separation and identification of its are of great significance for oil product developers to prepare high-performance lubricants. However, the extraction methods reported for base oils mainly adopt membrane dialysis, which not only fails to completely separate the base oil but also wastes a large amount of solvent. The reason for this result is that the concentration of substances inside and outside the membrane cannot always be in an imbalanced state of permeation resulting from manual operation. Additionally, most studies primarily focus on the characterization of base oil components, while there are few reports on grade identification. For the above reasons, an economically effective separation technique of base oil from low viscosity gasoline engine oil SN 0W-16 is successfully established by combining improved Soxhlet extraction and a column chromatography separation method. By applying this method, the yield of extracting base oil generally exceeds 96%, and the solvent can also save more than 3 times. Besides, an exclusion method is built through several simple characterization steps including viscosity index (VI), FT-IR, size-exclusion chromatography (SEC), and hydrocarbon composition, which can quickly identify the American Petroleum Institute (API) grade and brand of the base oils.

Carbon dots-loaded cellulose nanofibrils hydrogel incorporating Bi2O3/BiOCOOH for effective adsorption and photocatalytic degradation of lignin.

A novel photocatalytic adsorbent, a cellulose nanofibrils based hydrogel incorporating carbon dots and Bi2O3/BiOCOOH (designated as CCHBi), was developed to address lignin pollution. CCHBi exhibited an adsorption capacity of 435.0 mg/g, 8.9 times greater than that of commercial activated carbon. This enhanced adsorption performance was attributed to the 3D porous structure constructed using cellulose nanofibrils (CNs), which increased the specific surface area and provided additional sorption sites. Adsorption and photocatalytic experiments showed that CCHBi had a photocatalytic degradation rate constant of 0.0140 min-1, 3.1 times higher than that of Bi2O3/BiOCOOH. The superior photocatalytic performance of CCHBi was due to the Z-scheme photocatalytic system constructed by carbon dots-loaded cellulose nanofibrils and Bi2O3/BiOCOOH, which facilitated the separation of photoinduced charge carriers. Additionally, the stability of CCHBi was confirmed through consecutive cycles of adsorption and photocatalysis, maintaining a removal efficiency of 85 % after ten cycles. The enhanced stability was due to the 3D porous structure constructed by CNs, which safeguarded the Bi2O3/BiOCOOH. This study validates the potential of CCHBi for high-performance lignin removal and promotes the application of CNs in developing new photocatalytic adsorbents.

Combined Placental Mesenchymal Stem Cells with Guided Nanoparticles Effective Against Diabetic Nephropathy in Mouse Model.

Background: Diabetic nephropathy (DN) is a prevalent complication of diabetes mellitus and constitutes the primary cause of mortality in affected patients. Previous studies have shown that placental mesenchymal stem cells (PL-MSCs) can alleviate kidney dysfunction in animal models of DN. However, the limited ability of mesenchymal stem cells (MSCs) to home to damaged sites restricts their therapeutic potential. Enhancing the precision of PL-MSCs' homing to target tissues is therefore vital for the success of cell therapies in treating DN. Methods: We developed Fe3O4 coated polydopamine nanoparticle (NP)-internalized MSCs and evaluated their therapeutic effectiveness in a mouse model of streptozotocin- and high-fat diet-induced DN, using an external magnetic field. Results: Our study confirmed that NPs were effectively internalized into PL-MSCs without compromising their intrinsic stem cell properties. The magnetic targeting of PL-MSCs notably improved their homing to the kidney tissues in mice with DN, resulting in enhanced kidney function compared to the transplantation of PL-MSCs alone. Furthermore, the anti-inflammatory and antifibrotic attributes of PL-MSCs played a role in the recovery of kidney function and structure. Conclusion: These results demonstrate that magnetically targeted therapy using PL-MSCs is a promising approach for treating diabetic nephropathy.

KM04416 suppressed lung adenocarcinoma progression by promoting immune infiltration.

OBJECTIVES: Lung adenocarcinoma (LUAD) is a malignant tumor originating from the bronchial mucosa or glands of the lung, with the fastest increasing morbidity and mortality. Therefore, the prognosis of lung cancer remains poor. Glycerol-3-phosphate dehydrogenase 2 (GPD2) is a widely existing protein pattern sequence in biology and is closely related to tumor progression. The therapy values of GPD2 inhibitor in LUAD were unclear. Therefore, we aimed to analyze the therapy values of GPD2 inhibitor in LUAD. MATERIALS AND METHODS: The Cancer Genome Atlas (TCGA)-LUAD database was used to analyze the expression levels of GPD2 in LUAD tissues. The relationship between GPD2 expression and LUAD patient survival was analyzed by Kaplan-Meier method. Moreover, KM04416 as a target inhibitor of GPD2 was used to further investigate the therapy value of GPD2 inhibitor in LUAD cells lines (A549 cell and H1299 cell). The TISIDB website was used to investigate the associations between GPD2 expression and immune cell infiltration in LUAD. RESULTS: The results showed that GPD2 is overexpressed in LUAD tissues and significantly associated with poor survival. KM04416 can suppress the progression of LUAD cells by targeting GPD2. Low expression of GPD2 is related to high infiltration of immune cells. CONCLUSIONS: In summary, our present study found that targeting inhibition of GPD2 by KM04416 can suppress LUAD progression via adjusting immune cell infiltration.

Circadian clock component PER2 negatively regulates CD4+ T cell IFN-γ production in ulcerative colitis.

Period circadian clock 2 (PER2) is involved in the pathogenesis of various inflammatory and autoimmune diseases. However, there are gaps in our understanding of the role of PER2 in regulating CD4+ T cells beyond its time-keeping function in ulcerative colitis (UC) pathogenesis. Our findings revealed PER2 was predominantly expressed in CD4+ T cells, while it was significantly decreased in the inflamed mucosa and peripheral blood CD4+ T cells of UC patients compared with that in Crohn's disease (CD) patients and healthy controls (HC). Notably, PER2 expression was significantly recovered in UC patients in remission (R-UC) compared to that in active UC patients (A-UC) but not in CD patients. It was negatively correlated with the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Crohn's Disease Activity Index (CDAI), Simple Endoscopic Score for Crohn's disease (SES-CD), and C-reactive protein (CRP), respectively. Overexpression of PER2 markedly inhibited IFN-γ production in UC CD4+ T cells. RNA-seq analysis showed that overexpression of PER2 could repress the expression of a disintegrin and metalloproteinase 12 (ADAM12), a costimulatory molecule that determines Th1 cell fate. Mechanistically, cleavage under targets and tagmentation (CUT&Tag) analysis revealed that PER2 down-regulated ADAM12 expression by reducing its binding activity, thereby suppressing IFN-γ production in UC CD4+ T cells. Additionally, our data further demonstrated that ADAM12 was upregulated in CD4+ T cells and inflamed mucosa of A-UC patients compared to HC. Our study reveals a critical role of PER2 in regulating CD4+ T cell differentiation and highlights its potential as a therapeutic target for UC treatment.

Lung Abscess Caused by Tannerella forsythia Infection: A Case Report.

Background: Tannerella forsythia is a gram-negative anaerobic bacterium commonly found in the oral cavity. It is among the common pathogenic bacteria associated with gingivitis, chronic periodontitis, and aggressive periodontitis. However, there is currently no literature discussing lung abscesses primarily caused by T. forsythia infection. Presentation: This article presents the case of a 55-year-old male with a massive lung abscess. The patient underwent ultrasound-guided percutaneous drainage, and the sample was sent for pathogen metagenomic next-generation sequencing (mNGS) testing. The test indicated that the lung abscess was primarily caused by T. forsythia infection. A literature review was conducted to understand the characteristics of this pathogen as well as its clinical features and suitable treatment approaches. Conclusion: Currently, there is no literature specifically mentioning T. forsythia as a primary pathogen causing lung abscesses. This anaerobic bacterium is commonly found in the oral cavity and is difficult to cultivate using routine culture methods. mNGS emerges as a value diagnostic method for identifying this pathogen. Treatment recommendations include drainage and antibiotic selection encompassing common periodontal pathogens such as red complex bacteria and Actinomyces.

[New progress in the surgical treatment of laryngeal cyst in infants and children].

Laryngeal cyst is a cystic lesion occurring in the laryngeal cavity. Large laryngeal cyst in infants and young children can cause laryngeal wheezing and other upper airway obstruction symptoms. In severe cases, it can be even life-threatening and requires timely surgical treatment. Currently, there is a lack of unified clinical treatment strategy for this disease.This article summarizes the surgical methods, the advantages and disadvantages of various surgical methods for laryngeal cysts in recent years. It is recommended that needle aspiration, partial cyst wall resection, radical cyst dissection, transoral robotic surgery or external approach cyst resection should be selected through full communication and evaluation to clarify the extent of the lesion scope and the advantages and disadvantages of surgery.

Deep learning for the screening of primary ciliary dyskinesia based on cranial computed tomography.

Objective: To analyze the cranial computed tomography (CT) imaging features of patients with primary ciliary dyskinesia (PCD) who have exudative otitis media (OME) and sinusitis using a deep learning model for early intervention in PCD. Methods: Thirty-two children with PCD diagnosed at the Children's Hospital of Fudan University, Shanghai, China, between January 2010 and January 2021 who had undergone cranial CT were retrospectively analyzed. Thirty-two children with OME and sinusitis diagnosed using cranial CT formed the control group. Multiple deep learning neural network training models based on PyTorch were built, and the optimal model was trained and selected to observe the differences between the cranial CT images of patients with PCD and those of general patients and to screen patients with PCD. Results: The Swin-Transformer, ConvNeXt, and GoogLeNet training models had optimal results, with an accuracy of approximately 0.94; VGG11, VGG16, VGG19, ResNet 34, and ResNet 50, which are neural network models with fewer layers, achieved relatively strong results; and Transformer and other neural networks with more layers or neural network models with larger receptive fields exhibited a relatively weak performance. A heat map revealed the differences in the sinus, middle ear mastoid, and fourth ventricle between the patients with PCD and the control group. Transfer learning can improve the modeling effect of neural networks. Conclusion: Deep learning-based CT imaging models can accurately screen for PCD and identify differences between the cranial CT images.

Antibiotic treatment can exacerbate biofilm-associated infection by promoting quorum cheater development.

Quorum cheating, a socio-microbiological process that is based on mutations in cell density-sensing (quorum-sensing) systems, has emerged as an important contributor to biofilm-associated infection in the leading human pathogen Staphylococcus aureus. This is because inactivation of the staphylococcal Agr quorum-sensing system leads to pronounced biofilm formation, increasing resistance to antibiotics and immune defense mechanisms. Since biofilm infections in the clinic usually progress under antibiotic treatment, we here investigated whether such treatment promotes biofilm infection via the promotion of quorum cheating. Quorum cheater development was stimulated by several antibiotics used in the treatment of staphylococcal biofilm infections more strongly in biofilm than in the planktonic mode of growth. Sub-inhibitory concentrations of levofloxacin and vancomycin were investigated for their impact on biofilm-associated (subcutaneous catheter-associated and prosthetic joint-associated infection), where in contrast to a non-biofilm-associated subcutaneous skin infection model, a significant increase of the bacterial load and development of agr mutants was observed. Our results directly demonstrate the development of Agr dysfunctionality in animal biofilm-associated infection models and reveal that inappropriate antibiotic treatment can be counterproductive for such infections as it promotes quorum cheating and the associated development of biofilms.

Essential role of membrane vesicles for biological activity of the bacteriocin micrococcin P1.

Bacterial membrane vesicles (MVs) have recently gained much attention and have been shown to carry a wide diversity of secreted bacterial components. However, it is poorly understood whether MV carriage is an indispensable requirement for a cargo's function. Bacteriocins as weapons of bacterial warfare shape the composition of microbial communities. Many bacteriocins have pronounced hydrophobicity that is imposed by their mechanism of action, but how they diffuse through aqueous environments to reach their target competitors is not known. Here we show that antimicrobial competitive activity of an exemplary hydrophobic bacteriocin of the thiopeptide antibiotic family, micrococcin P1 (MP1), is dependent on incorporation into MVs, which were found to carry MP1 at high concentrations. In contrast, MP1 without MV association was poorly active due to low solubility. Furthermore, we provide previously unavailable evidence that MVs fuse with a Gram-positive bacterium's cytoplasmic membrane, in this case to deliver a bacteriocin to its intracellular target. Our findings demonstrate how bacteria overcome the problem associated with secreting hydrophobic small molecules and delivering them to their target and show that MVs have a key function in bacterial warfare. Furthermore, our study provides hitherto rare evidence that MVs provide an essential rather than merely accessory function in bacterial physiology.

Correction: In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model.

Correction for 'In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model' by Xiuying Li et al., Biomater. Sci., 2019, 7, 2861-2872, DOI: 10.1039/C9BM00242A.