Frontiers in Cellular and Infection Microbiology最新文献

Highly pathogenic avian influenza (HPAI) viruses of clade 2.3.4.4b continue to diversify through reassortment with co-circulating low-pathogenic avian influenza (LPAI) viruses and are repeatedly introduced into South Korea via migratory flyways. During national wild bird surveillance in October 2025, two HPAI viruses of different subtypes, H5N1 and H5N9, were detected in Common teals in the southwestern Korea. Whole-genome sequencing confirmed both isolates as clade 2.3.4.4b viruses belonging to the G2c sub-lineage. Phylogenetic analysis showed that the H5N1 virus possessed a genomic backbone related to the 22G4 genotype circulating in Korea during the 2022-2023 season, incorporating a PB1 segment derived from LPAI viruses. The H5N9 virus represented a distinct reassortant carrying an NA gene closely related to H11N9 LPAI viruses and internal segments associated with KorD and KorC genotypes prevalent in the same season. Bayesian time-scaled analysis indicated that both isolates originated from an East Asian H5Nx lineage with a common ancestor around 2019, and that the H5N1 virus diverged from a closely related Chinese strain in late 2023. Both viruses harbored multiple mammalian-adaptation markers, including substitutions commonly detected in recent East Asian HPAI strains. These findings demonstrate ongoing inter-lineage reassortment between regional HPAI and LPAI gene pools, emphasizing the continued role of migratory waterfowl in introducing emerging variants into Korea. The early-season detection of genetically distinct reassortants highlights the importance of sustained wild bird surveillance, rapid genomic characterization, and international data sharing to track the evolution and spread of newly emerging HPAI lineages.

Background: Infectious bovine rhinotracheitis virus (IBRV) is a primary pathogen causing bovine respiratory disease syndrome. This virus can cause rhinotracheitis and vaginitis in cattle, resulting in high mortality and posing a serious threat to bovine production. MicroRNAs (miRNAs), a class of regulatory non-coding small RNAs, can modulate viral replication by influencing host immune responses. However, reports on the association between host miRNAs and IBRV infection are limited.

Methods: In this study, we screened differentially expressed miRNAs in MDBK cells after IBRV infection and determined that the expression of bta-miR-146b was significantly increased. We investigated the effects of bta-miR-146b on IBRV replication and its underlying molecular mechanisms using molecular biological techniques such as luciferase activity assays, Western Blot, and qRT-PCR, together with bioinformatics approaches.

Results: We found that bta-miR-146b expression was up-regulated in IBRV-infected MDBK cells. Furthermore, transfection with bta-miR-146b mimics promoted IBRV replication in MDBK cells, whereas transfection with bta-miR-146b inhibitors inhibited IBRV replication, indicating that bta-miR-146b is a pro-infection factor. Additional studies showed that bta-miR-146b mimics inhibited type I interferon expression in MDBK cells, whereas its inhibitors enhanced it. Moreover, we identified IRAK1 as a direct target of bta-miR-146b and found that silencing IRAK1 expression rescued the effects of bta-miR-146b on viral replication and type I interferon expression.

Conclusion: These results suggest that bta-miR-146b regulates type I interferon expression and IBRV replication in MDBK cells by targeting IRAK1, and plays a key role in IBRV infection.

Objective: This study aimed to compare the effects of clear aligners (CA) and fixed appliances (FA) on periodontal indices, oral microbiota, and oxidative stress markers. Potential associations between microbial changes, oxidative stress, and periodontal health were also explored.

Methods: Twenty-four orthodontic patients matched at baseline were randomly allocated to the CA (n = 12) and FA (n = 12) groups. Saliva, supragingival plaque, and gingival crevicular fluid (GCF) were collected at baseline (T0), 3 months (T1), and 6 months (T2). Periodontal indices, including plaque index (PI), gingival index (GI), probing depth (PD), bleeding on probing (BOP) were recorded. Microbial composition was assessed via 16S rDNA sequencing. 8-Hydroxy-2'-deoxyguanosine (8-OHdG, a stable biomarker of oxidative DNA damage reflecting ROS levels) in saliva and GCF was quantified using double-antibody sandwich ELISA. Associations were analyzed using Spearman correlation.

Results: PI was significantly higher in the FA group than CA group at T1 (P < 0.01) and T2 (P < 0.05). BOP was higher in the FA group than CA group at T2 (P < 0.05). Pathogenic genera (Prevotella, Veillonella) were enriched in the FA group, while health-associated Rothia and Lautropia predominated in the CA group (P < 0.05). In GCF, 8-OHdG levels were higher in the FA group than CA group at T2 (P < 0.001). In saliva, Prevotella positively correlated with 8-OHdG in the FA group (r = 0.61, P < 0.05); Prevotella negatively correlated with Rothia in both groups (r = -0.90, P < 0.001).

Conclusions: Fixed appliances were associated with enrichment of pathogenic taxa, elevated oxidative stress markers, and worse periodontal indices, potentially linked to higher periodontitis risk. Clear aligners showed less microbial disruption and health-associated taxa enrichment. The Prevotella-8-OHdG-Rothia axis highlights microbiota and oxidative stress interactions as promising targets for preventing orthodontic treatment related periodontal complications.

Objective: Debridement, antibiotics, and implant retention (DAIR) is the preferred treatment for acute periprosthetic joint infection (PJI), yet its failure rate remains high, and the influencing factors are not fully elucidated. This study aimed to investigate the causes of DAIR failure in acute PJI and construct a risk prediction model based on clinical characteristics, inflammatory markers, and microbiological data.

Methods: A retrospective analysis was conducted on 90 patients with acute PJI treated at our medical center between January 2008 and April 2024. All patients underwent standard DAIR treatment and were categorized into success (n = 77) and failure (n = 13) groups based on outcomes. Demographic data, infection characteristics, laboratory markers, microbiological results, and surgical details were collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors, and a nomogram prediction model was developed.

Results: The overall success rate of DAIR was 85.6% (77/90). The failure group exhibited significantly higher rates of knee joint infection (84.6% vs. 50.6%, p=0.023), acute hematogenous infection (61.5% vs. 20.8%, p=0.005), preoperative peripheral White Blood Cell (WBC) (9.5×10^9/L vs. 8.2×10^9/L, p=0.043), CRP (79.6-4 mg/L vs. 42.4 mg/L, p<0.001), ESR (80.6 mm/h vs. 60.5 mm/h, p=0.002), synovial fluid WBC (35,300×10^6/L vs. 21,843×10^6/L, p=0.043), and synovial fluid polymorphonuclear leukocytes (PMNs) (91.7% vs. 83.8%, p<0.001) compared to the success group. Multivariate logistic regression identified acute hematogenous infection (OR 11.704, 95% CI 1.957-119.357, p=0.015), preoperative CRP (OR 1.022, 95% CI 1.009-1.040, p=0.003), synovial fluid PMN% (OR 1.196, 95% CI 1.039-1.454, p=0.039), and resistant pathogens (OR 0.107, 95% CI 0.010-0.665, p=0.032) as independent risk factors for DAIR failure. The nomogram model based on these factors demonstrated robust predictive performance.

Conclusion: DAIR failure is closely associated with hematogenous infection, the intensity of inflammatory response, and the presence of resistant pathogens. The proposed risk prediction model may aid clinical decision-making and optimize patient selection for DAIR.

Androgens are critical for the growth of prostate cells, as well as prostate tumor cells. For prostate cancer patients under Androgen Deprivation Therapy (ADT) such as castration treatment, investigating the potential for androgen production by gut microbes is crucial. In microbe species, the side chain cleavage activity of steroid-17, 20-desmolase (SSTD) is responsible for 11-oxy-androgens production by biotransformation from cortisol, as well as from other endogenous steroids and pharmaceutical glucocorticoids. The side-chain cleavage product of prednisone could significantly promote the proliferation of prostate cancer cells. The SSTD is a complex formed by N-terminal and C-terminal transketolases encoded by desA and desB genes, whose activity has been well-characterized in Clostridium scindens ATCC 35704. While a void still existed in evaluating the androgen producing potential by gut microbiota owing to relatively low abundance of SSTD-carrying species and the lack of professional gene database. Meanwhile, mining SSTD encoding genes in explosion sequencing data has become computationally expensive and time-consuming using comprehensive database. Here, a professional database consisted of SSTD-coding genes, named SSTDhunter, was constructed using a large-scale genomic analysis along with homologous genes as background. These SSTD-coding genes were reconstruction through comprehensive characteristics consisted of operon structures, sequence identities, phylogenetic topologies and comparative analysis. To reduce false positives, protein sequences of homologous genes tktA, which encode component of sugar transketolase, were also included in SSTDhunter database as background noise. SSTDhunter is for rapid investigation of SSTD-coding genes in massive metagenomic data, which is freely available at http://www.orgene.net/SSTDhunter/.

Cystic echinococcosis is an important parasitic zoonosis infecting numerous humans with high morbidity and mortality. As one of the etiologic agents, Echinococcus ortleppi infection in humans has been very rare. In this study, a 27-year-old man was diagnosed with cystic echinococcosis in Wuhan City of China, a non-endemic area. Next-generation sequencing identified that the etiologic agent was E. ortleppi. Its complete mitochondrion sequence (13,600 bp) has 99.92% identity to E. ortleppi from cattle in Japan. This is the third reported E. ortleppi infection case in China. Although extensive epidemiological investigations were performed, the infection source of this patient is still unclear. It is possible that there exists some hidden or unrecognized route of E. ortleppi transmission in China. Further investigation is needed to figure out and eliminate the risk factors.

Liver disease is increasingly common worldwide and poses significant challenges during anesthesia and surgery. Growing evidence demonstrates that the gut microbiome plays an essential role in hepatic inflammation, metabolic imbalance, immune dysfunction, and the progression of conditions such as metabolic associated steatotic liver disease, alcohol related liver injury, and cirrhosis. This review summarizes the concept of the gut-liver-anesthesia axis, which describes how disturbances in the intestinal microbiome shape perioperative risk. Importantly, this framework conceptualizes the gut-liver-anesthesia axis as a unified perioperative risk model, integrating microbial dysbiosis, hepatic vulnerability, and anesthetic exposure into a single pathophysiological continuum. Patients with advanced liver disease frequently exhibit reduced microbial diversity, impaired intestinal barrier function, disordered bile acid signaling, and heightened systemic inflammation. These alterations increase susceptibility to infection, kidney injury, hemodynamic instability, and neurocognitive complications including hepatic encephalopathy and postoperative delirium. Anesthetic agents can further disrupt the gut ecosystem by weakening mucosal integrity and facilitating bacterial translocation, while the microbiome itself influences drug metabolism and clearance, leading to unpredictable anesthetic responses. Understanding this bidirectional interaction highlights opportunities for microbiome focused perioperative strategies. Approaches such as probiotic based preparation, opioid sparing anesthesia, regional techniques, early enteral feeding, and targeted microbial restoration may improve postoperative outcomes in patients with liver disease.

Background: Streptococcus species are predominant ​commensal residents of the respiratory tract​ in healthy individuals and contribute to immune and metabolic regulation. However, the association between streptococcal colonization and clinical outcomes in patients with severe pneumonia remains undercharacterized. This study aimed to explore the clinical characteristics and the impact of streptococcal colonization on the prognosis of critically ill patients with pneumonia.

Method: We conducted a multicenter, retrospective, observational cohort study of critically ill pneumonia patients admitted to 12 intensive care units (ICUs) between January 2019 and December 2023 who underwent metagenomic next-generation sequencing (mNGS). Patients were stratified into Streptococcus-colonized and non-colonized groups based on bronchoalveolar lavage fluid (BALF) mNGS results, conventional microbiological testing (CMT), and clinical assessments. Propensity score matching (PSM) was utilized to minimize baseline confounding variables. Using nearest-neighbor matching at a 1:2 ratio, baseline characteristics were balanced between groups post-matching. The primary endpoint was 28-day all-cause mortality.

Results: A total of 1,897 patients were enrolled in this study. Among them, 21 patients under 18 years of age, 139 patients lost to follow-up within 28 days, and 4 patients with confirmed streptococcal infection were excluded. Finally, 1,733 patients met the inclusion criteria. The cohort had a mean age of 65 years, with the majority being males (1,213/1,733, 70%). Among these, 148 (8.5%) were classified as Streptococcus-colonized, and 1,585 (91.5%) were Streptococcus-colonization-negative. No significant difference in 28-day all-cause mortality was observed between the colonized and non-colonized groups (35.81% vs. 38.51%, p=0.578). Patients with Streptococcus colonization had a significantly shorter median length of stay (LOS) (17 days, interquartile range [IQR] 11-30) than those without colonization (22 days, IQR 12-33; P = 0.044). Similarly, their median intensive care unit (ICU) LOS (11 days, IQR 7-16) was also significantly shorter than that of non-colonized patients (14 days, IQR 8-25; P = 0.003). Multivariable Cox regression analysis further demonstrated that Streptococcus colonization was not an independent risk factor for 28-day mortality (HR = 1.10, 95% CI: 0.79-1.51, p=0.579).

Conclusion: Our findings suggest a potential role for Streptococcus colonization in improving clinical outcomes in severe pneumonia. The presence or absence of Streptococcus colonization may influence short-term prognostic benefits in critically ill pneumonia patients. Further research is needed to clarify the clinical significance and potential mechanisms of Streptococcus colonization.

Objective: Ceftazidime/avibactam (CZA), a combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam, was widely used in the treatment of multidrug-resistant (MDR) Gram-negative bacterial pathogens. In light of the growing prevalence of MDR Gram-negative bacterial infection, it is imperative to gain a deeper understanding of the true extent of adverse events (AEs) associated with CZA.

Methods: AE reports primarily associated with CZA were retrieved from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2015 to the first quarter of 2025, and all AEs were extracted. AE signal detection was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) methods. Additionally, a multivariable logistic regression analysis was performed to evaluate the safety of CZA combined with meropenem, explicitly adjusting for confounders such as age, sex, and concomitant nephrotoxins.

Results: A total of 2,444 AE reports with CZA as the preferred suspected drug were obtained, identifying 89 preferred terms (PTs) involving 24 system organ classes (SOCs). The ratio of males to females was approximately two times higher in all cases, with the highest number of reports originating from China. Some significant AE signals have been revealed by four methods, including renal and urinary disorders (n = 112, ROR 2.49, PRR 2.43, EBGM 2.43, IC 1.28) and hepatobiliary disorders (n = 98, ROR 5.04, PRR 4.88, EBGM 4.88, IC 2.29). Regarding combination therapy with meropenem, multivariable analysis revealed a specific safety signal: the risk of respiratory failure remained significantly elevated [adjusted OR (aOR) 3.26, P = 0.038] independent of baseline severity. Conversely, acute kidney injury showed no significant association (aOR 1.07, P = 0.868), suggesting that the respiratory risk is pharmacodynamically driven rather than a result of generalized clinical deterioration.

Conclusion: The present study identified significant and novel AEs signals for CZA. Notably, the specific association between the CZA-meropenem combination and respiratory failure warrants vigilant clinical monitoring, distinct from general disease progression risks.