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Frontiers in Immunology 2024Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability,... (Review)
Review
Extracellular vesicles (EVs), characterized by low immunogenicity, high biocompatibility and targeting specificity along with excellent blood-brain barrier permeability, are increasingly recognized as promising drug delivery vehicles for treating a variety of diseases, such as cancer, inflammation and viral infection. However, recent findings demonstrate that the intracellular delivery efficiency of EVs fall short of expectations due to phagocytic clearance mediated by the host mononuclear phagocyte system through Fcγ receptors, complement receptors as well as non-opsonic phagocytic receptors. In this text, we investigate a range of bacterial virulence proteins that antagonize host phagocytic machinery, aiming to explore their potential in engineering EVs to counteract phagocytosis. Special emphasis is placed on IdeS secreted by and ImpA secreted by , as they not only counteract phagocytosis but also bind to highly upregulated surface biomarkers αβ on cancer cells or cleave the tumor growth and metastasis-promoting factor CD44, respectively. This suggests that bacterial anti-phagocytic proteins, after decorated onto EVs using pre-loading or post-loading strategies, can not only improve EV-based drug delivery efficiency by evading host phagocytosis and thus achieve better therapeutic outcomes but also further enable an innovative synergistic EV-based cancer therapy approach by integrating both phagocytosis antagonism and cancer targeting or deactivation.
Topics: Extracellular Vesicles; Phagocytosis; Humans; Animals; Bacterial Proteins; Neoplasms; Integrin alphaVbeta3; Hyaluronan Receptors; Pseudomonas aeruginosa
PubMed: 38903499
DOI: 10.3389/fimmu.2024.1418061 -
Ugeskrift For Laeger Jun 2024Pseudomonas aeruginosa, a Gram-negative bacterium known to induce severe infections, is seldomly reported in scientific literature as a contributor of osteomyelitis. In...
Pseudomonas aeruginosa, a Gram-negative bacterium known to induce severe infections, is seldomly reported in scientific literature as a contributor of osteomyelitis. In this case report, a 71-year-old woman exhibited recurring infections and enduring forearm pain. A subsequent MRI revealed osteomyelitis in the distal ulna, linked to an arterial blood gas sample taken months earlier. Despite undergoing multiple extended courses of antibiotic treatment, the patient eventually underwent surgery on her left forearm. Biopsy cultures conclusively confirmed the presence of P. aeruginosa.
Topics: Humans; Female; Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Osteomyelitis; Ulna; Anti-Bacterial Agents; Magnetic Resonance Imaging; Punctures
PubMed: 38903032
DOI: 10.61409/V01240062 -
Scientific Reports Jun 2024A polyphasic approach was applied to characterize taxonomically a novel endophytic bacterial strain, designated as EP178, which was previously isolated from Passiflora...
A polyphasic approach was applied to characterize taxonomically a novel endophytic bacterial strain, designated as EP178, which was previously isolated from Passiflora incarnata leaves and characterized as plant-growth promoter. The strain EP178 forms Gram stain-negative and rod-shaped cells, and circular and yellow-pigmented colonies. Its growth occurs at 10-37 °C, at pH 6.0-8.0, and tolerates up to 7% (w/v) NaCl. The major cellular fatty acids found were summed feature 8 (C ω7c), summed feature 3 (C ω6c /C ω7c), and C, and the predominant ubiquinone was Q-9. The phylogenetic and nucleotide-similarity analysis with 16S rRNA gene sequences showed that strain EP178 belongs to Pseudomonas genus. The genomic-based G + C content was 65.5%. The average nucleotide identity and digital DNA-DNA hybridization values between strains EP178 and the closest type strain, P. oryzihabitans DSM 6835, were 92.6% and 52.2%, respectively. Various genes associated with plant-growth promoting mechanisms were annotated from genome sequences. Based on the phenotypic, genomic, phylogeny and chemotaxonomic data, strain EP178 represents a new species of the genus Pseudomonas, for which the name Pseudomonas flavocrustae sp. nov. was proposed. The type strain is EP178 (= CBMAI 2609 = ICMP 24844 = MUM 23.01).
Topics: Endophytes; Phylogeny; Pseudomonas; Passiflora; RNA, Ribosomal, 16S; Base Composition; Fatty Acids; DNA, Bacterial; Plant Leaves; Nucleic Acid Hybridization
PubMed: 38902258
DOI: 10.1038/s41598-024-64349-1 -
Bioresource Technology Jun 2024Limited information is available on the removal of per- and polyfluoroalkyl substances (PFAS) in anaerobic digestion (AD). Τhe fate of six PFAS was studied in...
Limited information is available on the removal of per- and polyfluoroalkyl substances (PFAS) in anaerobic digestion (AD). Τhe fate of six PFAS was studied in thermophilic bioreactors in the presence of granular activated carbon (GAC) and voltage application. Reactors with GAC exhibited lower concentrations of volatile fatty acids and higher methane production compared to those with and without the application of voltage. Analysis of PFAS in dissolved and solid phase showed that their distribution was dependent on perfluorocarbon chain length and functional group. Mass balances showed that PFAS were not removed during conventional AD or after applying voltage; however, significant removal (up to 61 ± 8 %) was observed in bioreactors with GAC for perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS). Biomass characterization showed that in these bioreactors, the relative abundance of Acinetobacter and Pseudomonas was higher, indicating their potential role in PFAS biotransformation.
PubMed: 38901748
DOI: 10.1016/j.biortech.2024.131013 -
PLoS Biology Jun 2024Fungi and bacteria coexist in many polymicrobial communities, yet the molecular basis of their interactions remains poorly understood. Here, we show that the fungus...
Fungi and bacteria coexist in many polymicrobial communities, yet the molecular basis of their interactions remains poorly understood. Here, we show that the fungus Candida albicans sequesters essential magnesium ions from the bacterium Pseudomonas aeruginosa. To counteract fungal Mg2+ sequestration, P. aeruginosa expresses the Mg2+ transporter MgtA when Mg2+ levels are low. Thus, loss of MgtA specifically impairs P. aeruginosa in co-culture with C. albicans, but fitness can be restored by supplementing Mg2+. Using a panel of fungi and bacteria, we show that Mg2+ sequestration is a general mechanism of fungal antagonism against gram-negative bacteria. Mg2+ limitation enhances bacterial resistance to polymyxin antibiotics like colistin, which target gram-negative bacterial membranes. Indeed, experimental evolution reveals that P. aeruginosa evolves C. albicans-dependent colistin resistance via non-canonical means; antifungal treatment renders resistant bacteria colistin-sensitive. Our work suggests that fungal-bacterial competition could profoundly impact polymicrobial infection treatment with antibiotics of last resort.
PubMed: 38900845
DOI: 10.1371/journal.pbio.3002694 -
Microbiology (Reading, England) Jun 2024Long-term administration of certain macrolides is efficacious in patients with persistent pulmonary infection, despite how limited the clinically achievable...
Long-term administration of certain macrolides is efficacious in patients with persistent pulmonary infection, despite how limited the clinically achievable concentrations are, being far below their MICs. An increase in the sub-MIC of macrolide exposure-dependent sensitivity to nitrosative stress is a typical characteristic of . However, a few clinical isolates do not respond to sub-MIC of macrolide treatment. Therefore, we examined the effects of sub-MIC of erythromycin (EM) on the sensitivity to nitrosative stress together with an efflux pump inhibitor (EPI) phenylalanine arginyl β-naphthylamide (PAβN). The sensitivity to nitrosative stress increased, suggesting that the efflux pump was involved in inhibiting the sub-MIC of macrolide effect. Analysis using efflux pump-mutant revealed that MexAB-OprM, MexXY-OprM, and MexCD-OprJ are factors in reducing the sub-MIC of macrolide effect. Since macrolides interfere with quorum sensing (QS), we demonstrated that the QS-interfering agent furanone C-30 (C-30) producing greater sensitivity to nitric oxide (NO) stress than EM. The effect of C-30 was decreased by overproduction of MexAB-OprM. To investigate whether the increase in the QS-interfering agent exposure-dependent sensitivity to nitrosative stress is characteristic of clinical isolates, we examined the viability of treated with NO. Although treatment with EM could reduce cell viability, a high variability in EM effects was observed. Conversely, C-30 was highly effective at reducing cell viability. Treatment with both C-30 and PAβN was sufficiently effective against the remaining isolates. Therefore, the combination of a QS-interfering agent and an EPI could be effective in treating infections.
Topics: Pseudomonas aeruginosa; Quorum Sensing; Microbial Sensitivity Tests; Anti-Bacterial Agents; Nitrosative Stress; Erythromycin; Membrane Transport Proteins; Furans; Dipeptides; Macrolides; Pseudomonas Infections; Humans; Bacterial Outer Membrane Proteins; Bacterial Proteins
PubMed: 38900549
DOI: 10.1099/mic.0.001464 -
MBio Jun 2024Chemosensory systems allow bacteria to respond and adapt to environmental conditions. Many bacteria contain more than one chemosensory system, but knowledge of their...
UNLABELLED
Chemosensory systems allow bacteria to respond and adapt to environmental conditions. Many bacteria contain more than one chemosensory system, but knowledge of their specific roles in regulating different functions remains scarce. Here, we address this issue by analyzing the function of the F6, F8, and alternative (non-motility) cellular functions (ACF) chemosensory systems of the model plant pathogen pv. tomato. In this work, we assign PsPto chemoreceptors to each chemosensory system, and we visualize for the first time the F6 and F8 chemosensory systems of PsPto using cryo-electron tomography. We confirm that chemotaxis and swimming motility are controlled by the F6 system, and we demonstrate how different components from the F8 and ACF systems also modulate swimming motility. We also determine how the kinase and response regulators from the F6 and F8 chemosensory systems do not work together in the regulation of biofilm, whereas both components from the ACF system contribute together to regulate these traits. Furthermore, we show how the F6, F8, and ACF kinases interact with the ACF response regulator WspR, supporting crosstalk among chemosensory systems. Finally, we reveal how all chemosensory systems play a role in regulating virulence.
IMPORTANCE
Chemoperception through chemosensory systems is an essential feature for bacterial survival, as it allows bacterial interaction with its surrounding environment. In the case of plant pathogens, it is especially relevant to enter the host and achieve full virulence. Multiple chemosensory systems allow bacteria to display a wider plasticity in their response to external signals. Here, we perform a deep characterization of the F6, F8, and alternative (non-motility) cellular functions chemosensory systems in the model plant pathogen pv. tomato DC3000. These chemosensory systems regulate key virulence-related traits, like motility and biofilm formation. Furthermore, we unveil an unexpected crosstalk among these chemosensory systems at the level of the interaction between kinases and response regulators. This work shows novel results that contribute to the knowledge of chemosensory systems and their role in functions alternative to chemotaxis.
PubMed: 38899869
DOI: 10.1128/mbio.00871-24 -
Kidney International Reports Jun 2024Gram-negative peritonitis (GNP) is associated with significant morbidity in children receiving long-term peritoneal dialysis (PD) and current treatment recommendations...
INTRODUCTION
Gram-negative peritonitis (GNP) is associated with significant morbidity in children receiving long-term peritoneal dialysis (PD) and current treatment recommendations are based on limited data.
METHODS
Analysis of 379 GNP episodes in 308 children (median age 6.9 years, interquartile range [IQR]: 3.0-13.6) from 45 centers in 28 countries reported to the International Pediatric Peritoneal Dialysis Network registry between 2011 and 2023.
RESULTS
Overall, 74% of episodes responded well to empiric therapy and full functional recovery (FFR) was achieved in 82% of cases. bacterial susceptibility to empiric antibiotics and lack of severe abdominal pain at onset were associated with a good initial response. Risk factors for failure to achieve FFR included severe abdominal pain at onset and at 60 to 72 hours from treatment initiation (odds ratio [OR]: 3.81, 95% confidence interval [CI]: 2.01-7.2 and OR: 3.94, 95% CI: 1.06-14.67, respectively), spp. etiology (OR: 1.73, 95% CI: 1.71-4.21]) and bacterial resistance to empiric antibiotics (OR: 2.40, 95% CI: 1.21-4.79); the risk was lower with the use of monotherapy as definitive treatment (OR: 0.40, 95% CI: 0.21-0.77). Multivariate analysis showed no benefit of dual antibiotic therapy for treatment of peritonitis after adjustment for age, presenting symptomatology, 60 to 72-hour treatment response, and treatment duration. Monotherapy with cefazolin in susceptible Enterobacterales peritonitis resulted in a similar FFR rate (91% vs. 93%) as treatment with ceftazidime or cefepime monotherapy.
CONCLUSION
Detailed microbiological assessment, consisting of patient-specific and center-specific antimicrobial susceptibility data, should guide empiric treatment. Treatment "deescalation" with the use of monotherapy and narrow spectrum antibiotics according to susceptibility data is not associated with inferior outcomes and should be advocated in the context of emerging bacterial resistance.
PubMed: 38899186
DOI: 10.1016/j.ekir.2024.03.031 -
Health Science Reports Jun 2024Multidrug and extensive drug-resistant was extracted from burn patients referring to burn centers in southwest Iran so that biofilm generation and antibiotic resistance...
BACKGROUND AND AIMS
Multidrug and extensive drug-resistant was extracted from burn patients referring to burn centers in southwest Iran so that biofilm generation and antibiotic resistance could be investigated.
METHODS
A specific primer was used to confirm all our considered 110 culture-positive reports on 345 burn patients. The resistance of to seven antibiotics and Colistin with minimum inhibitory concentration (MIC) was assessed. Biofilm formation was assessed by the phenotypic study of specimens under Congo red agar and microtiter plate assays.
RESULTS
One hundred and 10 clinical isolates taken from burn wound infections were validated. Among isolates, Piperacillin, Ceftazidime, Maeropenem, Gentamycin, and Gatifloacin had the highest resistance to antibiotics, while Ticarcillin-Clavulanic acid and Ceftolozane-Tazobactam showed the least resistance. MICs were then evaluated via the E test. Seven isolates were resistant to colistin. Colistin reference MICs for multidrug-resistant prevalence was 38%, while it was 22% for extensively drug-resistant (XDR) . One was pandrug-resistant (PDR). Under Congo red agar test, 66 isolates (67%) formed biofilms and black colonies, whereas 44 isolates (50%) had red colonies. In MTP, 76% formed biofilm. 40%, 32%, 21% of the isolates were strong, moderate, and weak biofilm formers, respectively, while 43% did not form biofilms.
CONCLUSION
The resistance to antimicrobial agents has largely challenged the control of the infection. Accordingly, a higher resistance occurred when the isolates were transferred to the patients. Less than 50% samples generated strong biofilms. Consequently, hygienic measurements are essential to inhibit transmission to hospitalized patients.
PubMed: 38899004
DOI: 10.1002/hsr2.2138 -
TheScientificWorldJournal 2024Ethnomedicinally, more than 2000 plants were found to be used in Nepal. Among them, the red colored rhizome of and the bark of have been used widely to treat muscle...
Ethnomedicinally, more than 2000 plants were found to be used in Nepal. Among them, the red colored rhizome of and the bark of have been used widely to treat muscle fatigue, bone pain, fever, postpartum hemorrhage, and thirst by healers in Kaski and Tanahun districts, Nepal. However, scientific evidence towards their traditional uses is lacking till December, 2023. Therefore, we report the phytochemicals, total phenolic content (TPC), total flavonoid content (TFC), total carbohydrate content (TCC), antioxidant and antibacterial activities of and extracts. Phytochemical analysis indicated that and extracts were potential sources of chemicals such as phenols, flavonoids, tannins, terpenoids, saponins, and carbohydrates. The TPC, TFC, and TCC of extracts were determined by using an ultraviolet visible spectrophotometer. Among the extracts tested, extracts showed the highest phenolic and carbohydrate contents of 208.33 ± 12.96 mg of gallic acid equivalent/g and 564.16 ± 2.92 mg of D-glucose equivalent/g of dry extract, respectively. Similarly, revealed the highest flavonoid content of 30.35 ± 0.1 mg quercetin equivalent/g of dry extract. The extract of and exhibited potent antioxidant activity by scavenging 2,2-diphenyl-1-picrylhydrazyl radicals with an IC of 25.9 g/ml and 31.07 g/ml, respectively. The antibacterial activity of the and extract against , and was determined using an agar-well diffusion protocol that revealed the potential antibacterial activity of against . The present study will help validate the traditional uses of rhizomes and barks as a healing medicine and inspire the researcher towards further research, development, and formulation.
Topics: Antioxidants; Anti-Bacterial Agents; Plant Extracts; Phytochemicals; Plant Bark; Rhizome; Nepal; Flavonoids; Microbial Sensitivity Tests; Phenols
PubMed: 38898935
DOI: 10.1155/2024/1119165