BMC Microbiology最新文献

Background: Xizang (formerly known as Tibet in English) has one of the highest tuberculosis (TB) incidence rates in China. The region's extreme altitudes (≥ 3000 m) and hypoxic environment present substantial challenges for conventional diagnostic methods. Additionally, the clinical and biological characteristics of TB at high altitudes remain poorly understood.

Method: TB-seq, a third-generation nanopore-targeted sequencing method, was used to analyze sputum samples from 158 confirmed pulmonary TB patients in Xizang. Bacterial load was quantified, a drug-resistance gene landscape was generated, and these findings were correlated with clinical phenotypes. A matched low-altitude group (< 1000 m) was included to investigate the effects of altitude on Mycobacterium tuberculosis biology.

Result: In Xizang, retreatment cases accounted for the majority of TB patients (58.23%). Type I TB was the most common form (79.75%), while non-type I forms were observed only in retreatment patients (P < 0.01). Bacterial load decreased significantly with increasing age (P < 0.001), was higher in retreatment cases (P = 0.013), and positively correlated with white blood cell and neutrophil counts (P < 0.05). Drug-resistant mutations were identified in 22.78% of patients, primarily as mono-resistance (63.9%), with key resistance-associated genes being rpsL (47.2%), rpoB (38.9%), and katG (33.3%). Compared to low-altitude controls, the high-altitude group had a significantly lower bacterial load (P < 0.01), reduced overall drug resistance (23.7% vs. 38.2%, P < 0.01), no rrs mutations, and a significantly lower pncA mutation rate (P < 0.05).

Conclusion: Tuberculosis in Xizang is marked by a high proportion of retreatment cases, low pathogen burden, and a reduced rate of drug resistance-associated gene mutations. Altitude appears to suppress bacterial quantity and may select for specific resistance mechanisms. These findings support the need for targeted TB control strategies in Xizang and underscore the complex interactions among the environment, the pathogen, and the host.

Background: Wound dressings, as tulles or hydrogels, are the devices of choice for the management of wounds and they are also made available to clinicians in formulations integrating silver nanoparticles as antibacterial agents. Nevertheless, the management of wounds is significantly affected by bacterial infections that limit healing to only 45% of the cases.

Results: Poly(epsilon-Lysine) branched peptides, called dendrons, were synthesised with different levels (also known as generations) of branching by an automated solid-phase peptide method. Production at hundreds of miligram scale and over 90% of purity were obtained. A study of the antimicrobial properties of these branched peptides, when in soluble form or used to impregnate commercial wound dressings, was performed on two bacterial species relevant to wound infections, Staphylococcus aureus and Pseudomonas aeruginosa. The data showed the antibacterial activity of these molecules, when presenting three generations of molecular branching, on Staphylococcus aureus both in planktonic and biofilm conditions.

Conclusions: The present study shows that hyperbranched poly(epsilon-Lysine) dendrons can be used for wound S. aureus infection prevention, as an alternative to silver, either in soluble form or when used to impregnate the fibres of clinically-available, tulle- or hydrogel-based wound dressings.

Background: Type 2 diabetes (T2D) presents clinical challenges due to its difficult early diagnosis and treatment insensitivity. Further, the relationship between gut microbiota and serum composition in T2D has not been fully characterized. This study aimed to determine the relationship between gut microbiome and serum metabolome in patients with T2D.

Methods: We collected fecal and serum samples from 30 T2D patients and healthy controls (HCs). The fecal microbiome composition was analyzed using 16S rRNA sequencing, and serum metabolites were detected by UHPLC-MS/MS. Alpha and beta diversity indices (Chao1, Shannon, PCoA, etc.) were calculated to assess microbial diversity and community structure. Differential metabolites were integrated to identify potential biomarkers, and random forest modeling was used for predictive analysis to investigate and validate the importance of specific gut microbial genera.

Results: The feces and blood of T2D patients demonstrated different characteristics of 20 differential microbiomes in the gut and 30 metabolite in the blood from HCs. Further, a significant correlation was observed between the gut microbiota and serum metabolomic profiles, reflecting the influence of the microbiota on metabolic activity. In addition, the states of T2D and HC groups were clearly distinguishable based on differences in gut microbes and metabolites, with the random forest model achieving excellent diagnostic performance (AUC values of 0.9764 and 0.9823, respectively).

Conclusions: Our study provides a comprehensive profile of changes in the microbiome and serum metabolomics, indicating their potential application as biomarkers for future diagnosis and treatment in T2D.

Mastitis caused by Staphylococcus aureus (S. aureus) poses a significant challenge in dairy farming because of its impact on animal health and milk production. Understanding the regulatory role of N6-Methyladenosine (m6A) modification in this disease remains crucial. Here, we used direct RNA sequencing (DRS) to explore transcriptomic changes in bovine mammary epithelial cells (BMECs) exposed to S. aureus (SA) compared to untreated controls (MEC). We identified 178 differentially expressed isoforms (DEIs) enriched in pathways such as the TNF signaling pathway, Kaposi's sarcoma-associated herpesvirus infection, IL-17 signaling pathway, NF-kappa B signaling pathway, and rheumatoid arthritis. Most DEIs in these pathways exhibited m6A modifications, with 18 DEIs implicated in inflammation. Functional assays revealed that S. aureus increased the m6A levels of CCL20 mRNA, enhancing its stability via an m6A-YTHDF2-dependent mechanism, which led to elevated CCL20 expression. Silencing YTHDF2 increased IL-6 and TNF-α levels, whereas IL-10 expression decreased. Western blotting confirmed the role of YTHDF2 by showing elevated PI3K, Akt, and NF-κB levels in SA-treated cells following YTHDF2 silencing. These findings suggest that m6A-mediated regulation of CCL20 in S. aureus-induced BMECs operates via the PI3K/Akt/NF-κB pathway. These findings underscore the significance of m6A-mediated CCL20 regulation in mastitis pathogenesis and suggest potential therapeutic strategies for managing this economically significant disease in dairy farming.