Frontiers in Cellular and Infection Microbiology最新文献

Introduction: Enterococcus faecalis, a common inhabitant of the feline gastrointestinal tract, has emerged as a significant pathogen causing urinary tract infections (UTIs) in domestic cats. The rise of multidrug-resistant E. faecalis strains and their propensity to form biofilms pose significant challenges in treatment. This study investigated the antibacterial and antibiofilm activities of hexagonal zinc oxide nanoparticles (ZnONPs) alone and in combination with streptomycin and Moringa oleifera leaf extract (MOLe) against multidrug-resistant E. faecalis isolates from feline UTIs.

Methods: Antimicrobial susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Biofilm formation was assessed using the crystal violet assay, and biofilm-associated genes (sprE, gelE, fsrABC) were detected by PCR. ZnONPs, Str/ZnONPs (streptomycin-loaded ZnONPs), and Str/MOLe@ZnONPs (streptomycin and MOLe-loaded ZnONPs) were characterized using FTIR, DLS, TEM, and SEM. The antibacterial and antibiofilm activities of the synthesized nanoparticles were evaluated through time-kill assays, well diffusion assays, and gene expression analysis.

Results: A high prevalence of multidrug resistance was observed among the E. faecalis isolates, with significant resistance to ampicillin, vancomycin, and streptomycin. Characterization studies revealed the successful encapsulation of streptomycin and MOLe within the ZnONPs.In vitro assays demonstrated that Str/MOLe@ZnONPs exhibited potent antibacterial and antibiofilm activities against the tested E. faecalis strains, significantly reducing bacterial growth and biofilm formation.

Discussion: The emergence of multidrug-resistant E. faecalis strains necessitates the development of novel therapeutic strategies. This study demonstrates the promising potential of ZnONPs, particularly those loaded with streptomycin and MOLe, in combating biofilm-forming E. faecalis. The synergistic effects of the combined formulation may offer a novel approach to overcome antibiotic resistance and improve the treatment outcomes of E. faecalis UTIs in domestic cats.

Introduction: Sepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ failure. Despite its significant global burden, the underlying mechanisms of immune dysfunction in sepsis remain incompletely understood. This study explores the role of DNA methylation in white blood cells in sepsis pathogenesis.

Methods: A prospective case-control study was conducted to compare DNA methylation profiles between patients with community-acquired sepsis and matched controls who had similar infections but did not develop sepsis. Whole blood samples from these patients were analyzed using the Infinium MethylationEPIC v2.0 kit, enabling genome-wide methylation analysis. Selected genes with differential methylation were validated by pyrosequencing.

Results: Significant differential DNA methylation patterns were identified between septic and non-septic individuals uising. Our results suggest that DNA methylation changes are closely linked to the pathophysiological processes of sepsis, influencing immune cell activation, inflammation, and organ dysfunction. The most prominent findings include the hypomethylation of immune-related genes (SERPINA1, AZU1, MPO, and SLX4), which were strongly correlated with clinical severity and inflammatory markers such as SOFA scores and PCT levels. Correlation analyses demonstrated significant associations between the methylation levels of these genes and clinical severity markers, such as SOFA score and PCT levels. Notably, SLX4 hypomethylation showed the highest predictive value for poor prognosis (AUC 0.821), while SERPINA1 hypomethylation exhibited strong diagnostic potential for sepsis (AUC 0.858).

Discussion: Our results underscore the potential of DNA methylation changes, particularly in immune-related genes, to enhance the early detection of sepsis and to stratify patients based on severity. Future research should explore the therapeutic implications of these epigenetic alterations in sepsis care.

Breast cancer is the most common malignancy in women worldwide. Changes in the microbiota and their metabolites affect the occurrence and development of breast cancer; however, the specific mechanisms are not clear. Gut microbes and their metabolites influence the development of breast cancer by regulating the tumor immune response, estrogen metabolism, chemotherapy, and immunotherapy effects. It was previously thought that there were no microorganisms in breast tissue, but it is now thought that there are microorganisms in breast cancer that can affect the outcome of the disease. This review builds on existing research to comprehensively analyze the role of gut and intratumoral microbiota and their metabolites in the development and metastasis of breast cancer. We also explore the potential function of the microbiota as biomarkers for prognosis and therapeutic response, highlighting the need for further research to clarify the causal relationship between the microbiota and breast cancer. We hope to provide new ideas and directions for the development of new methods for breast cancer treatment.

Introduction: Inflammatory bowel disease (IBD) represents a cluster of chronic idiopathic inflammatory disorders situated at the nexus of intricate interplays. The primary aim of the present investigation is to perform an umbrella review of metaanalyses, systematically offering a comprehensive overview of the evidence concerning risk factors for IBD.

Methods: To achieve this, we searched reputable databases, including PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews, from inception through April 2023. Two authors independently assessed the methodological quality of each metaanalysis using the AMSTAR tool and adhered to evidence classification criteria.

Results: In total, we extracted 191 unique risk factors in meta-analyses, including 92 significantly associated risk factors. The top ten risk factors were human cytomegalovirus (HCMV) infection, IBD family history, periodontal disease, poliomyelitis, campylobacter species infection, hidradenitis suppurativa, psoriasis, use of proton pump inhibitors, chronic obstructive pulmonary disease, and western dietary pattern.

Discussion: In conclusion, this umbrella review extracted 62 risk factors and 30 protective factors, most of which were related to underlying diseases, personal lifestyle and environmental factors. The findings in this paper help to develop better prevention and treatment measures to reduce the incidence of IBD, delay its progression, and reduce the burden of IBD-related disease worldwide.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023417175.

Background: Plasmodium vivax is a major cause of malaria, particularly outside Africa, necessitating effective strategies for public health management. Transmission-blocking vaccines (TBVs) have shown the potential to inhibit malaria transmission by targeting antigens expressed in sexual-stage parasites. Pbg37, a conserved protein expressed in sexual stages from gametocyte to ookinete in the rodent parasite P. berghei, is a viable target for TBV development.

Methods and findings: In this study, we constructed a transgenic strain, TrPvg37Pb, expressing Pvg37 using the P. berghei ΔPbg37 strain. Initial findings demonstrated that the replacement of Pbg37 with the exogenous Pvg37 did not impact parasite growth or development. Notably, Pvg37 was expressed during the gametocyte to ookinete development and was associated with the plasmic membrane, similar to Pbg37. To evaluate the potential of Pvg37 as a TBV candidate, we synthesized two Pvg37 polypeptides and immunized rabbits to generate antibodies. In vitro experiments demonstrated that anti-Pvg37-P2 antibodies significantly inhibited the formation of male gametes and ookinetes in the transgenic TrPvg37Pb parasite. Additionally, in mosquito feeding assays, mosquitos feeding on TrPvg37Pb-infected mice passively transferred with anti-Pvg37-P2 antibodies showed a significant 80.2% decrease in oocyst density compared to the control group. Furthermore, in direct membrane feeding experiments using four clinical P. vivax isolates, the anti-Pvg37 antibodies significantly reduced oocyst density by 28.6-50.4%.

Conclusion: Pvg37 is a promising candidate for P. vivax TBV development, deserving further research and optimization to enhance its immunogenicity and transmission-blocking activity.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) infections have become arduous to treat due to their capacity to form biofilms, develop persistence, and exhibit significant antimicrobial resistance. These factors contribute to the complexity of managing MRSA infections and highlight the urgent need for innovative treatment strategies.

Objectives: This endeavor aims to evaluate the safety of 2,2'-Bipyridine (2,2'-Bipy) derivatives and their antimicrobial, anti-biofilm, and anti-persister activities in treating MRSA Infections.

Methods: Six derivatives were screened for their ADMET properties and tested for minimum inhibitory concentrations against various bacterial strains using agar well diffusion and broth dilution. Safety studies were conducted through hemolysis tests, cell viability assays, and in vivo acute oral toxicity examinations. Bactericidal mechanisms and biofilm disruption effects were analyzed using crystal violet staining and confocal microscopy assays. The murine thigh infection model was also used to investigate the in vivo efficacy.

Results: All derivatives exhibited favorable physicochemical profiles and ADMET properties and are predicted to be safe based on their drug-like properties. in vitro studies demonstrated that derivatives are non-toxic to 3T3 L1, and in vivo studies confirmed their safety in mice at a dose of 300 mg/kg and their non-hemolytic nature against rabbit red blood cells. All compounds showed potent antibacterial activity against the tested bacteria, including the resistant MRSA strain 831. They inhibited biofilm formation and eradicated biofilms in a dose-dependent manner against MTCC 737 and MRSA 831, and they effectively eliminated MRSA persister cells, outperforming the reference antibiotic vancomycin. These derivatives were found to depolarize the mitochondrial membrane and accumulate intracellular reactive oxygen species. These derivatives significantly reduced the bacterial load in the murine thigh infection model.

Conclusion: The study concluded that 2,2'-Bipy derivatives possess significant antimicrobial activity, are non-toxic, and are effective in inhibiting biofilm formation and killing persister cells.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) caused an outbreak in 2002-2003, spreading to 29 countries with a mortality rate of about 10%. Strict quarantine and infection control methods quickly stopped the spread of the disease. Later research showed that SARS-CoV came from animals (zoonosis) and stressed the possibility of a similar spread from host to human, which was clearly shown by the COVID-19 outbreak. The COVID-19 pandemic, instigated by SARS-CoV-2, has affected 776 million confirmed cases and more than seven million deaths globally as of Sept 15, 2024. The existence of animal reservoirs of coronaviruses continues to pose a risk of re-emergence with improved fitness and virulence. Given the high death rate (up to 70 percent) and the high rate of severe sickness (up to 68.7 percent in long-COVID patients), it is even more critical to identify new therapies as soon as possible. This study combines research on antivirals that target SARS coronaviruses that have been conducted over the course of more than twenty years. It is a beneficial resource that might be useful in directing future studies.

Background: The capability of mNGS in diagnosing suspected LRTIs and characterizing the respiratory microbiome in lung cancer patients requires further evaluation.

Methods: This study evaluated mNGS diagnostic performance and utilized background microbial sequences to characterize LRT microbiome in these patients. GSVA was used to analyze the potential functions of identified genera.

Results: Bacteria were the most common pathogens (n=74) in LRTIs of lung cancer patients, and polymicrobial infections predominated compared to monomicrobial infections (p<0.001). In diagnosing LRTIs in lung cancer patients, the pathogen detection rate of mNGS (83.3%, 70/84) was significantly higher than that of sputum culture (34.5%, 29/84) (p<0.001). This result was consistent with that of non-lung cancer patients (p<0.001). Furthermore, in the specific detection of bacteria (95.7% vs. 22.6%) and fungi (96.0% vs. 22.2%), the detection rate of mNGS was also significantly higher than that of CMTs mainly based on culture (p<0.001, p<0.001). However, in the detection of CMV/EBV viruses, there was no significant difference between the detection rate of mNGS and that of viral DNA quantification (p = 1.000 and 0.152). mNGS analysis revealed Prevotella, Streptococcus, Veillonella, Rothia, and Capnocytophaga as the most prevalent genera in the LRT of lung cancer patients. GSVA revealed significant correlations between these genera and tumor metabolic pathways as well as various signaling pathways including PI3K, Hippo, and p53.

Conclusion: mNGS showed a higher pathogen detection rate than culture-based CMTs in lung cancer patients with LRTIs, and also characterizing LRT microbiome composition and revealing potential microbial functions linked to lung carcinogenesis.

The Gram-positive organism Filifactor alocis is implicated in multiple oral diseases including periodontitis, and approximately 50% of known strains encode and produce a recently identified repeat-in-toxin (RTX) protein, FtxA, partly homologous to the Aggregatibacter actinomycetemcomitans leukotoxin. By assessing a longitudinal Ghanaian study population of adolescents, we recently identified a possible correlation between F. alocis levels, ftxA gene carriage, and progression of clinical attachment loss (CAL). To extend knowledge on the possible significance of F. alocis and its FtxA in periodontal disease, we have in the present work analyzed saliva samples in an independent cohort of periodontitis (n=156), collected at two private periodontal specialist practices in Perth, Western Australia. The present results corroborate that high loads of F. alocis and the presence of its ftxA gene together are associated with parameters of periodontal tissue destruction and severity. Moreover, among the individuals carrying A. actinomycetemcomitans, a majority also exhibited an ftxA-positive F. alocis, supporting the notion of the synergistic behavior of these two species. This emphasizes that F. alocis and its ftxA are involved in the pathogenesis of periodontitis and may have ecological roles, with diagnostic and prognostic implications for the disease.

Background: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is linked to dyslipidemia and inflammatory responses. This study aimed to investigate the correlation between high-density lipoprotein cholesterol (HDL-C) levels and 90-day transplant-free (TF) mortality in patients with HBV-ACLF.

Methods: A prospective cohort of 287 patients with HBV-ACLF from Beijing Ditan Hospital was enrolled between January 2016 and December 2019. The prognostic accuracy of lipid profile parameters was evaluated by the area under the receiver operating characteristic curve (AUC), and the association between HDL-C levels and mortality was assessed using a restricted cubic spline analysis. Correlations between lipid profile parameters and inflammatory factors were analyzed. Kaplan-Meier curves were used to assess 90-day TF mortality, and log-rank tests were used for comparison analysis. These results were internally validated between January 2020 and December 2023 (n=125).

Results: Patients with lower HDL-C levels exhibited higher mortality rates (adjusted hazard ratio for HDL-C < 0.13 mmol/L: 4.04, 95% confidence interval: 1.35-11.85) compared with those in the reference group (with HDL-C levels above 0.36 mmol/L). An "L-shaped" association was observed between HDL-C levels and TF mortality. The prognostic value of HDL-C (AUC at day 90: 0.732) was comparable to the model for end-stage liver disease score of 0.729. Additionally, HDL-C levels were inversely correlated with interleukin (IL)-4, IL-6, and tumor necrosis factor-α (all P<0.05). In the training cohort, the 90-day TF mortality rates were 8.3%, 15.2%, 24.0%, and 43.2% for the extremely low, low, medium, and high-risk subgroups, respectively, while in the validation cohort, they were 4.5%, 18.5%, 31.2%, and 44.7%, respectively.

Conclusions: HDL-C levels < 0.13 mmol/L were associated with increased 90-day transplant-free mortality in patients with HBV-ACLF. An inverse correlation was found between HDL-C levels and inflammatory markers.