Microbial pathogenesis最新文献

Marine microorganisms offer a promising avenue for the eco-friendly synthesis of nanoparticles due to their unique biochemical capabilities and adaptability to various environments. This study focuses on exploring the potential of a marine bacterial species, Stenotrophomonas rhizophila BGNAK1, for the synthesis of biocompatible copper nanoparticles and their application for hindering biofilms formed by monomicrobial species. The study begins with the isolation of the novel marine S. rhizophila species from marine soil samples collected from the West coast region of Kerala, India. The isolated strain is identified through 16S rRNA gene sequencing and confirmed to be S. rhizophila species. Biosynthesis of copper nanoparticles using S. rhizophila results in the formation of nanoparticles with size of range 10–50 nm. The nanoparticles exhibit a face-centered cubic crystal structure of copper, as confirmed by X-Ray Diffraction analysis. Furthermore, the synthesized nanoparticles display significant antimicrobial activity against various pathogenic bacteria and yeast. The highest inhibitory activity was against Staphylococcus aureus with a zone of 27 ± 1.00 mm and the least activity was against Pseudomonas aeruginosa with a zone of 22 ± 0.50 mm. The zone of inhibition against Candida albicans was 16 ± 0.60 mm. The antibiofilm activity against biofilm-forming clinical pathogens was evidenced by the antibiofilm assay and SEM images. Additionally, the copper nanoparticles exhibit antioxidant activity, as evidenced by their scavenging ability against DPPH, hydroxyl, nitric oxide, and superoxide radicals, as well as their reducing power in the FRAP assay. The study highlights the potential of the marine bacterium S. rhizophila BGNAK1 for the eco-friendly biosynthesis of copper nanoparticles with diverse applications. Synthesized nanoparticles exhibit promising antibiofilm, antimicrobial, and antioxidant properties, suggesting their potential utility in various fields such as medicine, wastewater treatment, and environmental remediation.

Acne is one of the most common skin conditions worldwide, with multifactorial origins it affects areas of the skin with hair follicles and sebaceous glands that become clogged. Bacterial incidence aggravates treatment due to resistance to antimicrobial agents and production of virulence factors such as biofilm formation. Based on these information, this study aims to conduct in vitro evaluations of the antibacterial activity of essential oils (EOs), alone and in combination, against Propionibacterium acnes, Staphylococcus aureus, and Staphylococcus epidermidis in planktonic and biofilm forms. This study also assessed the anti-inflammatory potential (TNF-α) and the effects of EOs on the viability of human keratinocytes (HaCaT), murine fibroblasts (3T3-L1), and bone marrow-derived macrophages (BMDMs). Of all EOs tested, 13 had active action against P. acnes, 9 against S. aureus, and 9 against S. epidermidis at concentrations of 0.125–2.0 mg/mL. Among the most active plant species, a blend of essential oil (BEOs) was selected, with Cymbopogon martini (Roxb.) Will. Watson, Eugenia uniflora L., and Varronia curassavica Jacq., the latter due to its anti-inflammatory action. This BEOs showed higher inhibition rates when compared to chloramphenicol against S. aureus and S. epidermidis, and higher eradication rates when compared to chloramphenicol for the three target species. The BEOs did not affect the cell viability of cell lines evaluated, and the levels of TNF-α decreased. According to these results, the BEOs evaluated showed potential for the development of an alternative natural formulation for the treatment of acne.

Enterohemorrhagic Escherichia coli O157:H7 (EHEC O157:H7) and Enterotoxigenic E. coli (ETEC) have been found to readily develop biofilms on cucumber (Cucumis sativus L.), presenting a significant risk to the safety of ready-to-eat vegetables. This study aimed to assess the effectiveness of the lytic bacteriophage vB_EcoM_SQ17 (SQ17) against EHEC O157:H7 and ETEC biofilms on cucumber. Here, we evaluated the efficacy of phage SQ17 on the formation and reduction of biofilms formed by EHEC O157:H7 and ETEC strains on various surfaces, including polystyrene, poly-d-lysine precoated films, and fresh-cut cucumber, at different temperatures. Phage SQ17 significantly inhibited ETEC biofilm formation, reducing the number of adhered cells by 0.15 log CFU/mL at 37 °C. Treatment with phage SQ17 also significantly decreased the number of adhered cells in established biofilms via SEM observation. Moreover, phage SQ17 effectively reduced the biomass of EHEC O157:H7 and ETEC biofilms by over 54.8 % at 37 °C after 24 h of incubation. Following phage treatment, the viability of adhered EHEC O157:H7 cells decreased by 1.37 log CFU/piece and 0.46 log CFU/piece in biofilms on cucumber at 4 °C and 25 °C, respectively. Similarly, the viability of ETEC cells decreased by 1.07 log CFU/piece and 0.61 log CFU/piece in biofilms on cucumber at 4 °C and 25 °C, respectively. These findings suggest that phage SQ17 shows promise as a potential strategy for eradicating pathogenic E. coli biofilms on cucumber.

Background

Interferon-alpha (IFNα) is a common treatment for chronic hepatitis B virus (HBV) infection, but its efficacy varies widely among patients. GTPASE, an interferon-stimulated gene (ISG), has recently been identified as a factor in antiviral immunity, though its role in HBV infection is not fully understood.

Objective

This study investigates the role of GTPASE in enhancing the antiviral effects of IFNα against HBV and elucidates its mechanism of action.

Methods

We analyzed the impact of GTPASE overexpression and silencing on HBV replication and clearance in HBV-infected cells. Molecular docking studies assessed the interaction between GTPASE and HBV surface antigens (HBs). Clinical samples from HBV patients undergoing Peg-IFNα treatment were also evaluated for GTPASE expression and its correlation with treatment efficacy.

Results

Overexpression of GTPASE led to significant inhibition of HBV replication, increased HBeAg seroconversion, and enhanced HBsAg clearance. GTPASE directly bound to HBs proteins, reducing their levels and affecting viral particle formation. Silencing GTPASE reduced these effects, while combined treatment with Peg-IFNα and GTPASE overexpression further improved antiviral outcomes. Mutational analysis revealed that specific sites in GTPASE are crucial for its antiviral activity.

Conclusions

GTPASE acts as a positive regulator in IFNα-induced antiviral immunity against HBV. It enhances the therapeutic efficacy of IFNα by targeting HBs and modulating viral replication. GTPASE levels may serve as a predictive biomarker for response to Peg-IFNα therapy, highlighting its potential for improving individualized treatment strategies for chronic HBV infection.

Goose astroviruses (GAstVs) are important pathogens which can cause gout in goslings leading to huge economic losses for the goose farming industry in China. In 2023, an infectious disease characterized by visceral gout broke out in commercial goose farms in Guangxi and Guangdong provinces of China. In this study, two GAstV strains of GXNN and GDCS were successfully isolated from these two disease-ridden goose farms. The complete genomic lengths of these two strains were 7166 bp, and phylogenetic analysis showed that they were both GAstV-2 subtypes. The 3-dimensional structures of the capsid protein were predicted and six characteristic mutation sites at amino acid positions 60, 61, 228, 229, 456 and 523 were found within the strong antigenic regions. A recombination event occurred at 6833-7070 nt between the GAstV TZ03 and Turkey astrovirus CA/00 and this was detected in both the GXNN and GDCS strains. Another recombinant event occurred at 63–2747 nt between the GAstV XT1 and GAstV SDPY and this was detected in the GDCS strain. When 1-day-old goslings were infected with the novel GXNN and GDCS strains, they showed severe visceral gout. This was accompanied by enlarged spleens, liver hemorrhages and urate deposits in the kidneys and ureters and their blood urea nitrogen levels were significantly elevated. The mortality rates of the GXNN- and GDCS-infected groups were pathogenically high at 80 % and 60 %, respectively. These results will promote our understanding of the evolution and epidemic potential of GAstVs in China.

Staphylococcus aureus, a common human pathogen, has long been the focus of scientific investigation due to its association with various infections. However, recent research has unveiled a tantalizing enigma surrounding this bacterium and its potential involvement in carcinogenesis. Chronic S. aureus infections have been linked to an elevated risk of certain cancers, including skin cancer and oral cancer. This review explores the current state of knowledge regarding this connection, examining epidemiological evidence, pathogenic mechanisms, and biological interactions that suggest a correlation. Although initial studies point to a possible link, the precise mechanisms through which S. aureus may contribute to cancer development remain elusive. Emerging evidence suggests that the chronic inflammation induced by persistent S. aureus infections may create a tumor-promoting environment. This inflammation can lead to DNA damage, disrupt cellular signaling pathways, and generate an immunosuppressive microenvironment conducive to cancer progression. Additionally, S. aureus produces a variety of toxins and metabolites that can directly interact with host cells, potentially inducing oncogenic transformations. Despite these insights, significant gaps remain in our understanding of the exact biological processes involved. This review emphasizes the urgent need for more comprehensive research to clarify these microbiological mysteries. Understanding the role of S. aureus in cancer development could lead to novel strategies for cancer prevention and treatment, potentially transforming therapeutic approaches.

Integration of nucleic acid sequences of Reticuloendotheliosis virus (REV) in Avipoxvirus（APV） has become commonplace. In this study, 4 strains of suspected Fowlpox virus (FPV) and 1 strain of suspected Pigeonpox virus (PPV) collected in Taiyuan, Shanxi Province were cultured in chicken embryos, and the 4b core protein gene was amplified by PCR, and the identity and genome similarity were determined by sequence analysis. The sequences between the end of ORF201 and the beginning of ORF203 of FPV and PPV were then amplified, sequenced, and subjected to sequence comparison to determine genome similarity. The results showed that the isolates were 4 strains of FPV and 1 strain of PPV. The 4 isolated strains of FPV belong to type A1 virus, with 100 % identity to each other and to the FWPV-09-Jilin strain isolated in Jilin, China, and the lowest identity to the type B2 virus TNPV5/NZL/2009, which is only 74 %. PPV belongs to type A2 virus, and its identity with local strain of fowlpox virus was 90.1 %, with the highest identity of 100 % with PPLH and ROPI/W370/ON/2012 and ow_2017_3 strains, which also belong to type A2 pigeonpox virus, and the lowest identity of 73.7 % with TNPV5/NZL/2009, a type B2 virus. The complete genome of REV sequences integrated into FPV and PPV were amplified, and 5 REV nucleic acid sequences were obtained after sequencing and concatenation, with lengths ranging from 7942 to 8005 bp. The identity analysis results indicate that it has high identity with isolates from Northeast China, Guangdong, and Guangxi regions in China. Based on its gp90 protein gene, the REV integrated into the poxvirus belong to type III, with the highest identity of 99.9% with strains such as APC-566 and CY1111, and the lowest identity with REV-Anhui1, at 95.4 %. The length of the pol gene varies among different strains of REV, and its encoded amino acid changes significantly after position 675, with deletions and alterations. This study indicates that all fowlpox viruses isolated in Taiyuan, Shanxi Province have integrated the entire REV gene sequence, with high identity between them. At the same time, it indicates that the pigeonpox virus isolate has also integrated the entire REV gene sequence, and has the highest identity with the integrated REV gene sequence in fowlpox virus.

Pseudomonas aeruginosa infections have become a serious threat to public health due to the increasing emergence of extensively antibiotic-resistant strains and high mortality rates. Therefore, the search for new therapeutic alternatives has become crucial. In this study, the antivirulence and antibacterial activity of methyl gallate was evaluated against six clinical isolates of extensively antibiotic-resistant P. aeruginosa. Methyl gallate exhibited minimal inhibitory concentrations of 256–384 μg/mL; moreover, the use of subinhibitory concentrations of the compound inhibited biofilm formation, swimming, swarming, proteolytic activity, and pyocyanin production. Methyl gallate plus antipseudomonal antibiotics showed a synergistic effect by reduced the MICs of ceftazidime, gentamicin and meropenem. Furthermore, the potential therapeutic effect of methyl gallate was demonstrated in an infection model. This study evidenced the antivirulence and antimicrobial activity of methyl gallate as a therapeutic alternative against P. aeruginosa.

Background

Candida auris has been identified by the World Health Organization as a critical pathogen due to its invasive nature, resistance to multiple drugs, and high mortality rates in hospital outbreaks. This fungus can persist on surfaces and human skin for extended periods, complicating infection control efforts. The need for effective disinfection strategies is urgent, as current disinfectants are often ineffective against C. auris biofilms.

Objective

The study aimed to identify potential disinfectants from a collection of 240 compounds in the Global Health Priority Box® that are effective against C. auris, particularly strains resistant to existing options.

Methods

The research employed a screening protocol using a fluconazole-resistant strain of C. auris (149/23). Antifungal activity was assessed using the microdilution method to determine Minimum Inhibitory Concentrations (MICs) and Minimum Fungicidal Concentrations (MFCs). Additional assays were conducted to evaluate biofilm inhibition, biofilm eradication, cell membrane integrity, nucleotide leakage, sorbitol protection assay, efflux pump inhibition, and hemolysis assay.

Results

Two compounds, Hydramethylnon (MMV1577471) and Flufenerim (MMV1794206), demonstrated significant inhibitory effects against C. auris. Hydramethylnon exhibited potent antifungal activity, inhibiting up to 93 % of fungal growth with an MFC of 16 μg/mL. Flufenerim inhibited up to 58 % of fungal growth, showing fungistatic action with an MFC greater than 4 μg/mL. Biofilm inhibition tests showed that both compounds significantly inhibited biofilm formation, with increased efficacy at higher concentrations. Both compounds showed eradication rates in both stages. Furthermore, Hydramethylnon and Flufenerim did not affect cell membrane integrity or nucleotide leakage, suggesting a mode of action not reliant on disrupting these cellular components. The sorbitol protection assay revealed that neither compound caused cell wall damage. In the efflux pump inhibition assay, Hydramethylnon did not activate efflux pumps, while Flufenerim activated efflux pumps, reducing its effectiveness. Hemocompatibility assay showed safety.

Conclusion

The study highlights Hydramethylnon and Flufenerim as promising candidates for further development as disinfectants, offering potential solutions to the urgent need for effective disinfection agents against C. auris. The findings underscore the value of screening compound collections to identify novel antifungal agents and understand their mechanisms of action, thereby contributing to the advancement of new disinfection strategies in healthcare settings.

Short beak and dwarfism syndrome (SBDS) is attributed to Novel Goose Parvovirus (NGPV), which has inflicted significant economic losses on farming in China. Despite its significant impact, limited research has been conducted on the pathogenesis of this disease. The SD strain, a parvovirus variant isolated from ducks in Shandong province, was identified and characterized in our study. Phylogenetic analysis and sequence comparisons confirmed the classification of the SD strain as a member of NGPV. Based on this information, we established an animal model of SBDS by inoculating Cherry Valley ducks with the SD strain. Our findings indicate that infection with the SD strain leads to a reduction in body weight, beak length, width, and tibia length. Notably, significant histopathological alterations were observed in the thymus, spleen, and intestine of the infected ducks. Furthermore, the SD strain induces bone disorders and inflammatory responses. To evaluate the impact of NGPV on intestinal homeostasis, we performed 16S rDNA sequencing and gas chromatography to analyze the composition of intestinal flora and levels of short-chain fatty acids (SCFAs) in the cecal contents. Our findings revealed that SD strain infection induces dysbiosis in cecal microbial and a decrease in SCFAs production. Subsequent analysis revealed a significant correlation between bacterial genera and the clinical symptoms in NGPV SD infected ducks. Our research providing novel insights into clinical pathology of NGPV in ducks and providing a foundation for the research of NGPV treatment targeting gut microbiota.