Frontiers in Cellular and Infection Microbiology最新文献

Background: Healthcare-associated infections due to carbapenem-resistant Klebsiella pneumoniae (CRKP) are a global public health threat with rising hospital morbidity and mortality. We conducted a meta-analysis to systematically identify CRKP infection risk factors.

Methods: We searched Medline, Embase, Web of Science, and Cochrane Library for studies published January 1991-December 2024. Pooled odds ratio (OR)/95% confidence intervals (CIs) were used to assess risk factors; publication bias was evaluated via funnel plots and Egger's test, and robustness via leave-one-out sensitivity analysis.

Results: Fifty-one studies (13,860 patients: 4,711 CRKP cases, 9,149 carbapenem-susceptible K. pneumoniae controls) were included, with 43 reported risk factors. Thirty-one were significant: demographic/underlying diseases [male sex (OR = 1.31), kidney diseases (OR = 1.47), respiratory system diseases (OR = 2.69), cardiovascular diseases (OR = 1.34)]; invasive procedures [endoscopy (OR = 4.08), tracheal cannula (OR = 3.72), mechanical ventilation (OR = 3.61)]; medical environment [ICU admission (OR = 4.27), pre-infection hospital stay (mean difference=14.98 days)]; antibiotics [tigecycline (OR = 5.97), carbapenems (OR = 4.79), which may reflect disease severity, prior colonization]. Subgroup analysis showed regional heterogeneity: Western populations had higher risks with cephalosporins (OR = 2.68 vs. Eastern 1.55) and fluoroquinolones (OR = 3.58 vs. Eastern 1.89), while Eastern populations had higher risks with invasive procedures (dialysis: OR = 4.47 vs. Western 2.03). Sensitivity analysis confirmed robust results.

Conclusions: This meta-analysis reports endoscopy and surgical drainage as distinct subtypes of invasive procedural factors associated with hospital-acquired CRKP infection and describes regional differences in associated factors between Eastern and Western populations. These findings, based on observational evidence, provide preliminary insights for targeted prevention strategies.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024628428.

Objective: Interferon-based local therapy is an intervention for high-risk human papillomavirus (HR-HPV)-associated low-grade squamous intraepithelial lesions (LSIL) or lower-grade cervical abnormalities. This study sought to delineate the differences in clinical outcomes following interferon-based local drug treatment and elucidate the microenvironmental factors driving these disparities.

Methods: Cervical secretions, cell brush specimens, and cervical tissue samples were collected from patients with persistent HR-HPV infection and LSIL/lower-grade lesions at Shanghai First Maternity and Infant Hospital. Follow-up samples were obtained at 3 months post-treatment. Cervical secretions were subjected to 16S rRNA sequencing (to profile the microbiota) and cytokine quantification. Cell brush specimens were analyzed via transcriptome sequencing, while cervical tissue samples underwent immunohistochemical staining. Efficacy-related markers were assessed through both inter-group (independent comparisons) and intra-patient (self-paired) analyses.

Results: At the transcriptome level, the HR-HPV clearance group exhibited lower enrichment in pathways related to differentiation, keratinization, and development but higher enrichment in immune activation pathways compared to the persistence group at baseline (with a reversed pattern observed at follow-up). Baseline expression of TRAF3IP3, ZBP1, and IFI35 was higher in the clearance group, and ZDHHC11 expression remained consistently elevated. Immunohistochemical findings further demonstrated that the percentage of TRAF3IP3- and ZBP1-positive cells at baseline was significantly higher in the clearance group than in the persistence group. At the microbial level, treatment failure was associated with reduced Lactobacillus abundance, increased Gardnerella, Streptococcus anginosus, Schaalia turicensis, and Comamonadaceae abundance, alongside higher alpha diversity. Among cervical secretory cytokines, IL-2, IL-8, IL-12p70 showed inter-group differences, while IL-4 and IL-5 were barely detectable.

Conclusions: This study characterizes the cervical microenvironmental differences underlying divergent responses to interferon-based therapy, highlighting that coordinated changes in the microenvironment and immune status modulate treatment outcomes. The upregulated mRNA and protein levels of TRAF3IP3 and ZBP1 in the baseline period favor HR-HPV clearance, suggesting their potential as promising therapeutic targets.

Candidozyma auris (formerly Candida auris) has emerged as a formidable global health threat, characterized by its multidrug resistance (MDR), high transmissibility in healthcare settings, and significant mortality. The World Health Organization classifies it as a 'critical priority' fungal pathogen. Conventional infection control paradigms, often applying a 'one-size-fits-all' approach, have struggled to contain C. auris due to its unique environmental resilience and transmission dynamics. This review departs from traditional linear analyses and proposes a novel, scenario-based framework to deconstruct the complex challenges of C. auris management. We dissect the distinct transmission dynamics and control vulnerabilities across four high-risk clinical scenarios: the intensive care unit (ICU), long-term care facility (LTCF), high-risk surgical ward, and outpatient settings. Building on this analysis, we introduce the 'C. auris Integrated Control Bundle,' a multi-layered, adaptable toolkit combining patient-level, facility-level, and system-level interventions. This framework provides clinicians and infection preventionists with a practical, evidence-based paradigm to design and implement setting-specific, resource-optimized strategies against this resilient pathogen. We also review current diagnostic and therapeutic challenges, emphasizing the urgent need for rapid diagnostics and novel treatment options. By addressing key unanswered questions, this review aims to guide future research and strengthen the global response to C. auris.

Introduction: Biofilms formed by pathogenic bacteria such as Staphylococcus aureus and Escherichia coli pose a significant threat to public health. Combination therapy has emerged as a promising strategy to combat bacterial infections and biofilm formation. In this study, the natural product perillaldehyde and the surfactant domiphen were evaluated for their ability to inhibit biofilm formation by these pathogenic strains.

Methods: The antimicrobial activity of perillaldehyde and domiphen, alone and in combination, was assessed against S. aureus and E. coli strains. Synergism was determined by calculating the fractional inhibitory concentration index. Biofilm mass was evaluated using the crystal violet staining assay, and the viability of biofilm cells on stainless steel and polyethylene surfaces was examined via viable cell counting. Additionally, the therapeutic potential of the combination was further assessed using a Galleria mellonella larval infection model.

Results: The combination of perillaldehyde and domiphen showed synergistic effects against both pathogenic strains, with a fractional inhibitory concentration index of less than 0.36. The combination of 1 μL/mL perillaldehyde and 1 μg/mL domiphen dispersed more than 53% of the biofilm mass in both S. aureus and E. coli strains. In addition, the combination reduced the total viable bacterial counts in biofilms on stainless steel and polyethylene surfaces by approximately 103 CFU/mL. The treatment also significantly improved the survival rate of G. mellonella larvae infected with the bacteria.

Discussion: These results indicate that the novel combination of perillaldehyde and domiphen has the potential to decrease biofilm formation on various industrial material surfaces.

Purpose: Infections caused by clinical carbapenem-resistant Acinetobacter baumannii (CRAB) are associated with an increased risk of mortality and present a significant challenge for hospitals worldwide. This study aims to analyze the molecular epidemiological characteristics, drug resistance traits, and virulence features of CRAB isolated from bronchoalveolar lavage fluid (BALF) at a hospital in Ningxia, China.

Methods: We collected clinical characteristic data of patients with isolated strains and conducted statistical analysis. Antibiotic susceptibility testing was conducted using the VITEK-2 compact system. Carbapenemase and virulence genes were examined through PCR and Sanger sequencing. Multilocus Sequence Typing (MLST) was performed according to the Oxford MLST scheme by comparing the obtained sequences with known allele sequences available on the MLST website (http://pubmlst.org/abaumannii/). The virulence of CRAB was assessed using the Galleria mellonella infection assay.

Results: The results indicated that all tested CRAB strains carried the bla _OXA-23 and bla _OXA-51 genes, exhibiting multidrug resistance characteristics while remaining sensitive to polymyxins. MLST typing revealed that ST195 and ST369 strains were the most prevalent, with several other types identified, including ST208, ST136, ST469, ST368, and a rare ST1779. Notably, 94.2% of CRAB belonged to Global clone 2. Significant clinical differences were observed between ST195 and non-ST195 infection cases. Virulence assessment results indicated that 71 strains (58.6%) exhibited high virulence characteristics. Additionally, virulence factors such as ompA, adeH, pgaA, abal, BasJ, and plcD were detected in all tested strains, confirming an evolutionary trend towards high virulence in CRAB, which poses a serious threat to clinical treatment and patient prognosis.

Conclusion: The emergence of highly virulent multidrug-resistant CRAB strains in the Ningxia region has increased a clinical burden, highlighting the importance of clinical surveillance and diagnosis of these strains.

[This corrects the article DOI: 10.3389/fcimb.2026.1666138.].

Introduction: Antibiotic resistance poses a critical and escalating global health crisis, leading to higher morbidity and mortality associated with infectious diseases. This problem is significantly exacerbated by intracellular bacterial pathogens, which are often shielded from conventional antibiotics and foster the emergence of persister populations. Recently, host-directed therapy (HDT) has been emerging as a promising strategy that aims to modulate host cellular processes or immune responses to enhance bacterial clearance. Nonetheless, the inherent complexity of host biology makes identifying appropriate and safe modulators challenging, unpredictable, and highly complicated.

Methods: Here, we present a cell-based high-throughput screen (HTS), coupled with an intracellular-induced reporter that was used to screen a library of nearly 37,000 small molecules with potentially pharmacological activity for compounds that inhibit host cell infection by intracellular pathogens.

Results and discussion: This multistage, screening protocol resulted in the identification of eight non-cytotoxic compounds that efficiently inhibited the intracellular growth of the Gram-negative bacterium Salmonella Typhimurium in human epithelial cells by ~2.5- to 6-fold, without inhibiting Salmonella growth in culture. Five of these eight molecules were also effective in controlling the intracellular replication of Salmonella in primary mouse macrophages by 1.5- to 38-fold. Strikingly, seven hits also inhibited the intracellular growth of the Gram-positive bacterial pathogen Listeria monocytogenes in epithelial cells by 1.5- to 10-fold. The structure-activity relationship approach successfully identified chemical analogs of one hit with enhanced biological activity as infection inhibitors. Overall, we describe a robust HTS platform that can be adapted for screening of compound libraries against other pathogens, and suggest that the identified compounds are potential candidates for downstream development of novel drugs against intracellular bacterial infections.

In the modern era, the expanding demand for implants has transformed the healthcare system by restoring and enhancing the function of various biological structures, thereby increasing the patients' quality of life. These include urinary catheters, dental, orthopedic, cardiovascular implants, and sutures designed to perform various functions. However, these devices are more prone to microbial attack, contributing to biofilm formation mainly caused by multidrug-resistant ESKAPE pathogens, thereby increasing the risk of implant-associated infections and implant failure. This review summarizes the diverse array of implants available on the market and their associated infections caused by biofilm-producing pathogens, with a particular emphasis on the ESKAPE pathogen. Specific keywords were used to conduct a literature review using Google Scholar, Web of Science, PubMed, and Scopus databases. The data were then screened and integrated to explore the underlying principles of biofilm formation, its consequences, diagnostic approaches, and therapeutic studies. Currently, various methods are employed to diagnose these infections, including culture-based methods (tissue swab, culture, sonication) and non-culture methods (Dithiothreitol, XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide), Resazurin, BioTimer assays, and PCR). However, these studies indicate an increased difficulty in detecting infections caused by ESKAPE pathogens due to biofilm formation, highlighting the need for developing novel strategies. The recent advancements in the development of antimicrobial coatings, implant surface modifications, phage therapy, nanoparticles, antimicrobial peptides, and quorum-sensing inhibitors have shown promise in controlling these infections. Thus, these findings underscore the importance of research on innovative approaches and the development of infection-resistant implants, thereby reducing the clinical burden and improving patient outcomes.