Frontiers in Cellular and Infection Microbiology最新文献

Introduction: Rotavirus (RV) is a major cause of childhood gastroenteritis, leading to intestinal damage, inflammation, and gut microbiota dysbiosis. This study investigated whether ellagic acid (EA), a natural polyphenol, can alleviate RV-induced intestinal injury by modulating both host immunity and the gut microbiota.

Methods: In this study, RV was used to infect BALB/c suckling mouse models to explore whether ellagic acid could alleviate intestinal damage following rotavirus infection through bidirectional regulation of "immunity and microbiota". The viral load of RV, the expression levels of IL-1β, IL-6, and TNF-α mRNA were detected by qPCR. The pathological changes in the jejunal tissue were observed by hematoxylin and eosin (H&E) staining. The expression of JAM1, ZO-1, and Claudin-4 proteins in jejunal tissue were detected by immunohistochemistry (IHC). The expressions of TLR4, MYD88, IκBα, and P-P65 proteins in jejunal tissues were detected by WB. 16S rDNA gene sequencing was employed to detect the structural changes of the microbiota in feces, and qPCR was used to detect the colonization of Lactobacillus johnsonii, Lactobacillus reuteri, and Lactobacillus gasseri in jejunal tissues.

Results: The qPCR results revealed that ellagic acid could significantly (P < 0.001) reduce the viral load as well as the mRNA expression levels of IL-1β, IL-6, and TNF-α in RV-infected BALB/c suckling mice. The results of H&E staining demonstrated that ellagic acid could alleviate villus rupture and vacuolation lesions induced by RV and significantly (P < 0.05) alleviate intestinal villus shortening and crypt deepening caused by RV. The IHC results showed that ellagic acid could significantly increase the expression of tight junction proteins JAM1, ZO-1, and Claudin-4 in RV-infected BALB/c neonatal mice. The WB results showed that ellagic acid significantly (P< 0.001) inhibited the expression of the TLR4/NF-κB signaling pathway. The results of 16S rDNA gene sequencing showed that ellagic acid could lead to a significant (P < 0.05) increase in the abundance of intestinal Lactobacillus bacteria (Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus gasseri, etc.) in RV-infected BALB/c suckling mice. Ellagic acid can also significantly promote the colonization of Lactobacillus johnsonii, Lactobacillus reuteri, and Lactobacillus gasseriin the jejunum.

Discussion: Ellagic acid can alleviate intestinal damage following rotavirus infection through bidirectional regulation of "immunity and microbiota", providing a theoretical foundation and innovative concepts for the research and development of EA as an anti-RV drug.

Introduction: After COVID-19 pandemic, there has been an upward trend in Mycoplasma pneumoniae (M. pneumoniae) infections across Asia. The COVID-19-induced immunological impairment may increase the risk of adverse outcomes in M. pneumoniae-infected patients, yet studies in this area remain limited. We investigated the association between M. pneumoniae infection and adverse pregnancy outcomes in the post-COVID-19 era.

Methods: We conducted a single-center cohort study in Guangzhou, China, from February 2023 to June 2024, involving pregnant women. A total of 186 participants were included, with 49 in the M. pneumoniae group (tested positive for M. pneumoniae immunoglobulin M antibody (MP IgM)) and 137 in the control group. Propensity score weighting analysis was performed to control bias and estimate the effect size.

Results: The incidence of adverse pregnancy outcomes in the M. pneumoniae group was not significantly different from that in the control group. The odds ratio (OR) for adverse maternal events after propensity score weighting (PSW) was 1.25 (95% confidence interval [CI], 0.62 to 2.55; p = 0.530), and the PSW OR for adverse neonatal events was 0.95 (95% CI, 0.49 to 1.84; p = 0.884). However, in the subgroups of advanced maternal age (AMA, age ≥ 35, n=29) and primiparous women (n=80), the incidence of adverse pregnancy outcomes was significantly higher in the M. pneumoniae group. Additionally, the clinical manifestations of M. pneumoniae infection in the post-COVID-19 era were consistent with those observed prior to the pandemic.

Conclusions: In the post-COVID-19 era, evidence remains insufficient to conclude that M. pneumoniae infection increases the risk of adverse pregnancy outcomes in the general pregnant population. Exploratory subgroup analyses suggest possible signals of risk within subgroups of AMA and primiparous women.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that develops after 20 weeks of gestation, characterized by hypertension and proteinuria or multi-organ dysfunction. representing a leading cause of maternal and perinatal morbidity and mortality worldwide. The pathogenesis of PE is complex and remains incompletely understood, involving shallow placentation, endothelial dysfunction, immune imbalance, and systemic inflammation;however, the initiating triggers remain are unclear. Recent research has highlighted the gut microbiota-often termed the "second genome" -for its critical role in metabolic and immune homeostasis. Dynamic alterations in maternal gut microbial composition during pregnancy are closely associated with maternal and fetal health. Concurrently, placental exosomes, have emerged as key mediators of intercellular communication. These membrane-bound extracellular vesicles, released by placental cells, are capable of delivering microRNAs, proteins, and lipids into the maternal circulation to exert systemic effects. The emerging concept of a "gut microbiota-placental -exosome axis" suggests a pivotal role in PE progression. This review explores the bidirectional interactions between gut microbiota and placental exosomes, their regulatory impact on maternal-fetal immune crosstalk and endothelial function, and their contribution to PE pathophysiology. We also identify current research gaps and propose future directions, offering a theoretical basis for early biomarkers and targeted therapies for PE.

Background: Hemin is a major source of iron for pathogens in infectious niches. The FecIRA-like surface signaling cascade is a common regulatory system for iron acquisition by pathogens. This system consists of a FecA-like TonB-dependent transporter (TBDT), a FecR-like inner membrane anti-sigma factor, and a FecI-like extracytoplasmic function (ECF) sigma factor. Beyond iron acquisition, FecIRA-like systems have been reported to regulate additional physiological processes. The known hemin acquisition system in Stenotrophomonas maltophilia includes HemA, a TBDT; HemU, an inner membrane transporter; and the TonB1-ExbB1-ExbD1a-ExbD1b complex, a multi-subunit motor that energizes HemA. Fur and HemP are the primary regulators involved in hemin utilization. In this study, we identified a novel FecIRA-like regulatory system, i.e., HemI-HemR-HemA_D.

Methods: The regulatory role of HemI was examined using promoter-xylE transcriptional fusion constructs and real-time PCR. Mutants associated with the hemI-hemR-hemA_D operon were generated and evaluated for iron utilization, swimming motility, oxidative stress tolerance, and antibiotic susceptibility.

Results: The hemI-hemR-hemA_D operon was repressed by Fur-Fe²⁺ under iron-replete conditions. Its expression was partially derepressed under iron depletion and further derepressed in the presence of hemin; however, the operon showed no autoregulation. HemI was essential for hemin acquisition. The overexpression of hemI in the S. maltophilia KJ strain increased the susceptibility to levofloxacin (LVX) and trimethoprim-sulfamethoxazole (SXT). All S. maltophilia isolates examined displayed increased minimum inhibitory concentrations (MICs) for ceftazidime (CAZ) and minocycline (MIN) under the iron-depleted and hemin-available conditions; notably, the changes in the MICs of LVX and SXT were strain-dependent.

Conclusion: HemI, a novel ECF sigma factor, not only regulates hemin acquisition but also contributes to antibiotic susceptibility under iron-limited and hemin-available conditions.

Introduction: This study aimed to evaluate the value of inflammation and nutrition markers in predicting the failure of prosthesis removal and antibiotic bone cement spacer implantation (PRABCSI) for periprosthetic joint infection (PJI) treatment.

Materials and methods: Data from 78 patients with PJI who received PRABCSI were retrospectively analyzed. Patients were divided into a successful group and a failed group according to the outcome at the last follow-up. Patient demographics and laboratory values (white blood cell count, hemoglobin, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], ESR and CRP ratio [ESR/CRP], lymphocytes, platelet count [PLT], albumin, CRP and albumin ratio [CAR], and prognostic nutritional index [PNI]) were compared.

Results: The successful group had lower levels of CRP, ESR/CRP, PLT, and CAR compared to the failed group. Conversely, the successful group had higher levels of albumin and PNI. The markers with the highest predictive value for PRABCSI failure were CRP and CAR. Elevated levels of CRP and low levels of CAR were associated with a higher risk of PRABCSI failure.

Conclusions: CRP>35.43 and CAR>0.847 are associated with a higher risk of PRABCSI failure in PJI treatment and may serve as preoperative risk-stratification tools.

Signal transducer and activator of transcription 3 (STAT3) serves as a critical regulatory molecule in a multitude of physiological processes, encompassing cell proliferation, differentiation, immune defense, and inflammatory responses. The interaction between STAT3 and viruses is highly intricate, with particular relevance to the viral life cycle. It is widely acknowledged that during viral infection, the phosphorylation of STAT3, which is triggered by upstream activators such as interleukin-6 (IL-6), can exert an effective inhibitory effect on viral invasion. However, accumulating evidence has demonstrated that viruses may exploit their interaction with STAT3 to evade host immune surveillance, thereby facilitating viral persistence. Furthermore, the excessive activation of STAT3 induced by viral infection directly promotes viral replication. The precise mechanism underlying the role of STAT3 in viral infection and pathogenicity remains to be further elucidated. In this review, we summarize recent findings regarding the critical roles of STAT3 in host-virus interactions. Additionally, we discuss the mechanisms of related molecules involved in the antiviral immune response.

Background: Helicobacter pylori (H. pylori) represents a widespread chronic bacterial infection that has garnered increasing attention in recent years due to its extra-gastric effects. Remnant cholesterol (RC) is recognized as a non-traditional lipid marker and is a significant predictor of residual risk in atherosclerotic cardiovascular disease. This investigation aimed to analyze the correlation between H. pylori infection and RC levels, as well as to reveal the underlying mechanisms.

Methods: The study population comprised individuals undergoing routine health examinations at the health examination center of Taizhou Hospital. All participants were subjected to urea breath tests, blood tests, and anthropometric measurements. The triglyceride-glucose (TyG) index was utilized to assess insulin resistance (IR) levels, while the erythrocyte sedimentation rate (ESR) was utilized as an indicator of chronic inflammation levels within the population. To assess the relationship between H. pylori infection and RC, a multiple linear regression analysis was carried out, also investigating the mediating roles of the TyG index and ESR.

Results: Multiple linear regression analysis demonstrated a significant association between H. pylori infection and RC levels, with this relationship being stable across diverse populations. Mediation analysis further revealed that the TyG index and ESR significantly mediate the relationship between H. pylori and RC levels. Moreover, longitudinal analysis demonstrated that persistent H. pylori infection results in a marked increase in RC levels.

Conclusion: Our research identified an association between H. pylori infection and elevated RC levels, with IR and inflammation acting as mediating factors in this relationship.

Background: Immunological, metabolic, and hormonal changes occur during pregnancy, which can affect the composition and function of the microbiota in diverse body sites. These changes can influence pregnancy outcomes and the health of the mother and baby. We aimed to characterize the microbiota of pregnant women across various body sites and examine the clinical and population-specific factors associated with its composition. The role of lactobacilli in genitourinary infections during pregnancy was analyzed as well.

Material and methods: One hundred and five pregnant women with gestational age between 15 and 20 weeks were recruited from the Women's Clinic of Tartu University Hospital, Estonia. Microbiota samples of the cervix (C, n = 84), vagina (V, n = 85), urine (U, n = 105), mouth (M, n = 85), and rectum (R, n = 84) were analyzed using Illumina NextSeq2000.

Results: Firmicutes was the most common phylum in all investigated locations, with a mean proportion of over 50%. Lactobacillus was the most abundant genus in C, V, and U samples (mean proportions of 76%, 77%, and 59%, respectively), while its mean relative abundance was significantly lower in oral (2.8%) and rectal (6.2%) samples. Lactobacillus iners was the most frequent Lactobacillus species in genitourinary samples, followed by L. unidentified (unid)/crispatus, L. jensenii, and L. gasseri. The mean relative abundance of L. iners and L. unid/crispatus in these locations was relatively equal (36% vs. 32% in C, 35% vs. 33% in V, 25% vs. 27% in U). Higher diversity of total urogenital microbiota was associated with chorioamnionitis and metroendometritis at delivery and genitourinary infections during the second half of pregnancy. The latter was associated with lower Lactobacillus species diversity in C, V, and U samples. These women also had a lower proportion of L. unid/crispatus (in C and V samples) and L. gasseri (in C, V, and U samples), while they had a higher proportion of L. iners in C samples and a higher proportion of other bacteria in C and U samples.

Conclusions: The microbiota of pregnant women is linked to health profile and lifestyle factors and varies in different body regions; however, it is remarkably similar in the cervix and vagina. Higher abundance of Lactobacillus species in mid-pregnancy, particularly L. crispatus and L. gasseri, potentially provides protection against later genitourinary tract infections during pregnancy. This research underscores the importance of microbiota in maternal health and provides a foundation for future studies aimed at developing more effective strategies to support healthy pregnancy.

Background: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) represents a critical public health threat in China, characterized by the convergence of multidrug resistance and hypervirulence. The emergence of ceftazidime/avibactam (CZA) resistance further complicates clinical management. This study aimed to elucidate the molecular epidemiology, risk factors, and resistance mechanisms of CZA resistance in CR-hvKP across China, providing evidence for targeted interventions.

Methods: A single-center molecular epidemiological analysis was conducted on 81 Carbapenem-resistant Klebsiella pneumoniae (CRKP) clinical isolates collected. All isolates underwent whole-genome sequencing for MultiLocus Sequence Typing, capsule typing, and identification of resistance genes (blaKPC-2 and blaNDM-1) and virulence factors (iucA, iroB, rmpA, rmpA2, and peg-344). CZA resistance mechanisms were investigated through broth microdilution minimum inhibitory concentration (MIC) testing and bioinformatics analysis. Galleria mellonella infection models were employed to assess virulence potential. Risk factors were analyzed using multivariate regression of clinical variables. Phylogenetic reconstruction employed single-nucleotide polymorphism-based analysis.

Results: ST11 accounted for 96.15% (50/52) of CR-hvKP isolates, with K64 being the predominant capsule type (92.31%, 48/52). Additionally, 98.77% (80/81) of CRKP carried ≥1 virulence gene; 64.2% (52/81) of isolates with all five virulence genes exhibited lethality. Galleria mellonella revealed that the survival rate of CR-hvKP was lower than that of carbapenem-resistant non-hypervirulent Klebsiella pneumoniae (p<0.05). Antibiotic usage time (odds ratio [OR]=1.076, 95% confidence interval [CI]: 1.026-1.138), carbapenem antibiotic (OR = 0.117, 95% CI: 0.02266-0.4602), and malignant tumors (OR = 65.1, 95% CI: 7.078-1798) predicted CR-hvKP infection. Transferable blaKPC-2 on IncFII/IncR plasmids conferred CZA resistance (MIC>128 mg/L) without compromising carbapenem resistance, facilitated by a unique genetic context (TnpR_Tn3-ISKpn27-blaKPC-2-ISKpn6).

Conclusion: China faces a rapid dissemination of ST11 CR-hvKP clones carrying diversified CZA resistance mechanisms. The convergence of hypervirulence and resistance in ST11 lineages-accelerated by invasive procedures and international transmission-demands enhanced genomic surveillance. CZA resistance arises through multiple pathways, necessitating combination therapies and stewardship programs limiting prolonged CZA use. Our findings underscore an urgent need for rapid diagnostics targeting emergent resistance determinants and infection control measures to contain high-risk clones.