Microbes and Infection最新文献

Most studies on Haemophilus influenzae in the course of COPD focus on occurrence of this species in the respiratory tract. However, the relationship between the intestinal microbiota and the respiratory tract, may play a role in the course of COPD. Our study examined the presence of Haemophilus spp. in the oral cavity, respiratory tract and large intestine, and the level of anti-H. influenzae antibodies in patients during acute exacerbations of COPD (AECOPD). An additional goal was to identify the potential microbiota components co-occurring with Haemophilus spp. The study included 35 patients with AECOPD and the control group (23 people). Haemophilus spp. were isolated from 20 % patients in the AECOPD and 17.39 % from the control group, the difference was not statistically significant (p = 0.74). Mean levels of anti-H. influenzae antibodies were 0.491 ± 0.871 μg/ml in the AECOPD group and 1.021 ± 1.421 μg/ml in the control group, the difference was not statistically significant (p = 0.332). Greater diversity within Streptococci and Gram-negative bacilli was found in biological materials from AECOPD. We noted a more common frequency of isolation of Haemophilus spp. from the large intestine of AECOPD, which may indicate the occurrence of gut dysbiosis during exacerbations. The analysis of selected associated species showed that the bacteriological status of a COPD patient may influence the frequency and course of exacerbations.

Exopolysaccharides (EPS) are extracellular metabolites secreted by various bacteria, including lactic acid bacteria (LAB). EPS vary in structure and their composition depends on a number of production factors. In particular, they are used as thickeners to improve the organoleptic properties of foods. In any case, they can also have beneficial effects on human well-being, such as prebiotic effects, antioxidant effects, antimicrobial effects, and modulation of the immune system. This review aims to summarize the results of recent research on EPS produced by LAB in the regulation of intestinal health by acting as prebiotic and antimicrobial agents, as well as their antioxidant, hypocholesterolemic and immunomodulatory effects.

Influenza A virus (IAV) is a global respiratory pathogen, with macrophages playing a key role in innate immunity. We established mouse models of IAV-induced pneumonia and macrophage depletion, along with an in vitro co-culture system of lung epithelial cells (MLE-12) and macrophages (RAW264.7), to study IAV infection. HE staining, immunohistochemistry, and immunofluorescence revealed IAV-induced lung damage and macrophage recruitment. In the co-culture system, IAV infection caused morphological changes in both cell types, increased viral load, and elevated inflammatory factors. High-throughput sequencing identified miR-1260 and Sema3A-mediated PI3K/AKT/mTOR pathway involvement. Transfection with miRNA mimics, inhibitors, and Sema3A-siRNA showed that miR-1260 exacerbates cell damage by targeting Sema3A via PI3K/AKT/mTOR. Macrophage-depleted mice exhibited worse outcomes (weight loss, inflammation, viral load, pathology) than IAV-infected mice, linked to miR-1260/Sema3A/PI3K/AKT/mTOR regulation. Macrophages protect against IAV by suppressing miR-1260-mediated Sema3A/PI3K/AKT/mTOR activation.

Toxoplasma gondii infection in pregnant females can cause congenital toxoplasmosis. Although maternal and infant immune profiles appear to play a role, studies on this topic are scarce. We analyzed SNPs in the regulatory regions of cytokine genes in 30 mother-newborn pairs, five mothers and two infants with known status, with respect to vertical transmission and the clinical outcome of those infected. Polymorphisms in the IL-2, IL-10, IL-12, IL-17, TNF-α, and TGF-β1 gene promoter or regulatory regions were obtained by sequencing, and genotype and allele frequencies were related to transmission and clinical outcome of the offspring. In children, the polymorphic "G" TNF-α -308 allele, as well as the related low- and high-level homozygous GG or TT genotypes of the 3'UTR region of the IL-12reg gene, were associated with congenital infection. Both cytokines have been shown to be expressed in the cyto- and syncytiotrophoblast; therefore, the fetus might be able to regulate infection at the placental level. In mothers of infected children, the T allele of the IL-12reg 3'UTR gene was associated with more severe disease in their offspring, suggesting that a strong maternal response reduces parasite spread in the fetus. Furthermore, SNPs in the promoter region of IL-2 and TGF-β1 genes were associated with elevated levels and milder disease in children with congenital infection, which is congruent with a regulation of a strong, damaging, inflammatory response. Our results suggest that some up and down regulatory cytokine genes may predispose to vertical transmission or disease severity in congenital toxoplasmosis.

Co-infections involving Pseudomonas aeruginosa and Candida auris are becoming increasingly common in hospitals and represent an emerging clinical challenge, as these pathogens can form mixed biofilms during catheter-associated infections, which complicates treatment, prolongs the disease and poses a significant threat to public health. In this study, we formed individual- and dual-species biofilms with Pseudomonas aeruginosa and Candida auris, and then treated mature biofilms with or without meropenem to determine the number of viable cells (colony-forming units). Moreover, Pseudomonas aeruginosa biofilms plus total or fractionated Candida auris supernatant were exposed to meropenem to calculate biofilm-associated viable cells. The results showed that Pseudomonas aeruginosa exhibits increased survival to meropenem in dual-species biofilms compared to individual-species biofilms. Furthermore, we demonstrated that the molecule that promotes meropenem tolerance is present in the supernatant of Candida auris biofilms with a molecular mass <10 kDa. In conclusion, Candida auris induces meropenem tolerance in Pseudomonas aeruginosa during mixed biofilms.

Introduction: Oral squamous cell carcinoma (OSCC) exhibits aggressive behavior and poor prognosis. Porphyromonas gingivalis (P. gingivalis) affects the tumor microenvironment, but its role in ferroptosis inhibition in OSCC remains unclear. This study explores the impact of P. gingivalis on ferroptosis through SIRT5 upregulation.

Materials and methods: OSCC cell lines (Cal27, SCC9) were treated with the ferroptosis inducer RSL3, with or without P. gingivalis infection. Cell viability, ferroptosis markers (MDA, ROS, GPX4), and cell behavior (proliferation, migration, invasion) were assessed. SIRT5 and downstream targets (IDH2, GCLC) were analyzed using Western blot, qRT-PCR, and immunofluorescence. A SIRT5 knockdown model was used to evaluate its role in ferroptosis resistance.

Results: P. gingivalis infection increased OSCC cell survival, reduced ROS and MDA levels, enhanced GPX4 expression, and promoted proliferation, migration, and invasion. Elevated SIRT5 and its targets IDH2 and GCLC were observed. SIRT5 knockdown reversed ferroptosis resistance.

Conclusion: The findings suggest that P. gingivalis plays a critical role in promoting OSCC malignancy by inhibiting ferroptosis through the upregulation of SIRT5. This highlights the potential of targeting SIRT5 as a therapeutic strategy to counteract the effects of P. gingivalis in OSCC.

Objectives: Gram-negative bacteria (GNB) bloodstream infection (BSI) pose a significant clinical challenge in patients with haematological malignancy, further complicated by rising carbapenem-resistant GNB (CRGNB) prevalence. This study aims to investigate the prevalence and risk factors for GNB BSI and associated mortality in this population.

Methods: A retrospective study was conducted at a tertiary teaching hospital in southern China (2015-2023), including haematological malignancy patients with GNB BSI. Multivariate logistic analyses were performed to identify risk factors for CRGNB BSI and to establish a predictive model for 30-day mortality of GNB BSI.

Results: Among 351 patients with GNB BSIs, acute myeloid leukaemia (51.3 %) was the predominant underlying disease. Escherichia coli (28.8 %) and Klebsiella pneumoniae (29.7 %) were the most common GNB BSI and CRGNB BSI pathogens, respectively. Independent risk factors for CRGNB BSI included chronic liver disease, prior carbapenems therapy (≤30 days before BSI), a platelet count <30 × 10⁹/l and albumin concentration <30 g/l before BSI. The 30-day mortality prediction model of GNB BSI incorporated CRGNB infection, platelet count <30 × 10⁹/l and albumin concentration <30 g/l before BSI, demonstrating good discrimination (training cohort AUC: 0.828; validation cohort: 0.791). Calibration plots and decision curve analysis confirmed robust model performance.

Conclusions: Identified factors enable risk stratification for CRGNB BSI and poor prognosis in GNB BSI, facilitating timely interventions to improve outcomes.

Rapid advancements in artificial intelligence (AI) and machine learning (ML) offer significant potential to transform medical microbiology diagnostics, improving pathogen identification, antimicrobial susceptibility prediction and outbreak detection. To address these opportunities and challenges, the ESCMID workshop, "Artificial Intelligence and Machine Learning in Medical Microbiology Diagnostics", was held in Zurich, Switzerland, from June 2-5, 2025. The course featured expert lectures, practical sessions and panel discussions covering foundational ML concepts and deep learning architectures, data interoperability, quality control processes, model development and validation strategies. Key applications discussed included whole-genome sequencing for antimicrobial resistance detection, AI-enhanced digital microscopy automation and MALDI-TOF mass spectrometry-based diagnostics. Participants gained hands-on experience with essential AI tools and platforms. Special emphasis was placed on standardised laboratory protocols, regulatory compliance and ethical considerations, including data governance and patient privacy. Panel sessions further highlighted critical issues of equity, global disparities in AI access, sustainability and environmental impacts related to AI infrastructure. The workshop concluded by underscoring a necessity for ongoing interdisciplinary collaboration, continued education, and substantial investment in equitable AI infrastructure to realise the full potential of AI in clinical diagnostics.

Background: While autophagy is pivotal in antimicrobial defense, its regulatory role in Talaromyces marneffei (TM) infected bronchial epithelium remains elusive.

Objective: To elucidate the impact of TM infection on autophagy in bronchial epithelial cells and to identify the key molecular regulators involved in this process.

Methods: Primary computational screening identified core autophagy modulators. Autophagy flux was monitored through LC3B-II/P62 immunoblotting and transmission electron microscopy. Mechanistic validation was performed using siRNA-mediated FOXO3 silencing, lentivirus-mediated lncSSBP1 knockdown and overexpression cell models, combined with immunofluorescence staining for nuclear localization.

Results: Bioinformatics analysis identified seven autophagy modulating effectors, with FOXO3 emerging as the central regulator. Quantitative proteomics revealed biphasic autophagic responses: initial LC3B-II accumulation with P62 degradation at 4h post-infection, followed by P62 rebound at 24h, indicating time-dependent flux impairment. FOXO3 was identified as a critical mediator of TM-induced autophagy. Furthermore, we identified a strong positive correlation between lncSSBP1 and FOXO3 expression, with lncSSBP1 overexpression enhancing FOXO3 levels and promoting autophagosome maturation.

Conclusion: This study uncovers a previously unrecognized lncRNA-mediated regulatory axis wherein lncSSBP1 orchestrates FOXO3-driven autophagy during TM infection. These results provide new insights into the molecular mechanisms of host-pathogen interactions.