Frontiers in Cellular and Infection Microbiology最新文献

The vaginal microbiome of healthy women is dominated by Lactobacillus spp. A variety of illnesses, such as vaginosis, sexually transmitted infections (STIs), failed implantation, premature birth (PTB), and preterm pre-labor membrane rupture, are brought on by an unbalanced microbiota. Pregnancy is associated with a decrease in the metabolic capacity of the vaginal resident microbiome, which is consistent with a change to a less complex Lactobacillus-dominated microbiome. Age, race, sexual intercourse, smoking, IUD, contraception, lifestyle, and diet all affect the makeup of the vaginal microbiome. Moreover, physiological events including menarche, the menstrual cycle, pregnancy, menopause, and other hormonal changes have an impact on the vaginal microbiome. The vaginal microbiome is significantly disrupted by the menstrual cycle, with significant changes toward a more varied microbiota occurring around menstruation. Several major factors maintain or disrupt the vaginal microbiome including ethnic group, menstruation cycle, and pregnancy which are discussed in this section. In the index pregnancy, the vaginal microbiota of women who had already given birth, or had just experienced an induced or spontaneous abortion, was qualitatively and quantitatively different from that of women who were having their first child. Early pregnancy vaginal microbiome depletion is a risk factor for early pregnancy miscarriage. Although, early pregnancy miscarriage is not always caused by a high bacterial diversity and quantity of lactobacilli. Lactobacillus protects against pathogens through the production of antibacterial compounds such as lactic acid and bacteriocins.

About 71% of healthcare-associated infections are due to antibiotic-resistant bacteria, such as carbapenem-resistant A. baumannii, classified by World Health Organization into a critical priority group of pathogens. The antimicrobial resistance profile of A. baumannii relies on its ability to produce several virulence factors, including biofilm formation. Its ability to adhere and persist on surfaces as biofilm has contributed to its pathogenicity and drug resistance. In this study, the ability of an antimicrobial peptide (a chionodracine-derived peptide named KHS-Cnd) to inhibit or reduce biofilm formation was investigated as an example of a potential strategy to counteract infections caused by biofilm-forming pathogens. To this aim, the antimicrobial profiles were first analyzed in selected A. baumannii strains, two reference and six clinical strains, all biofilm-forming with different capability, regardless of whether they are drug resistant or sensitive. Successively, we investigated the bactericidal activity of the peptide that showed MIC values ranging from 5 to 10 µM and a significative antibiofilm activity on all tested strains at sub-inhibitory concentrations. In fact, KHS-Cnd can hinder biofilm A. baumannii strains formation with an inhibition percentage ranging between 65% and 10%. Also a statistically significant reduction of mature biofilm ranging from 20% to 50% was observed in four out of eight tested A. baumannii strains. KHS-Cnd impacts various stages of biofilm formation, including the inhibition of surface-associated and twitching motilities depending on the different strain. In particular, our results showed that only two strains possessed surface-associated motility that was strongly impaired by KHS-Cnd treatment; three clinical strains, instead, showed twitching motility, whose inhibition for two of them was evident after 24 h of incubation with peptide. Moreover, the invasion of pulmonary cells by A. baumannii was significantly impaired with a reduction of about 32% after treatment with 1.25 µM KHS-Cnd. Finally, when the peptide was used together with ceftazidime/avibactam against resistant A. baumannii strains, it was able to reduce the minimal inhibitory concentration of antibiotics needed to inhibit the microorganism growth.

This study aimed to investigate the relationship between gut microbiota composition, fecal metabolites, and postoperative prognosis in patients with extrahepatic cholangiocarcinoma (eCCA). A total of 53 patients with resectable eCCA and 21 healthy volunteers as a control group were included. 16S rRNA gene sequencing and metabolomic analyses revealed significant differences in the gut microbial community structure and altered fecal metabolites profiles between eCCA patients and healthy controls. Univariate and multivariate Cox regression analyses indicated that factors such as preoperative total bilirubin, indirect bilirubin, and specific metabolites were closely associated with overall survival in patients with eCCA post-surgery. The constructed nomogram model further demonstrated the predictive value of these factors, achieving a C-index of 0.718, with calibration curves confirming its strong predictive performance. In conclusion, gut microbiota composition and fecal metabolites play a crucial role in the surgical prognosis of eCCA patients, providing new insights for clinical prognostic assessment.

Introduction: The Hong Kong oyster (Crassostrea hongkongensis), as the main marine aquaculture shellfish in the South China Sea, not only has high economic and ecological value, but also is an ideal model for conducting research on pathogen-host interactions. In the cultivation process of C. hongkongensis, there is a challenge posed by vibrios. To improve the antibacterial strains of C. hongkongensis, we have studied the gene associated with immunity, PDIA3.

Methods and findings: In this study, we cloned the PDIA3 sequence of the C. hongkongensis, using the RACE technique. It has a total of 2081 bp and contains a 5'-UTR of 55 bp and a 3'-UTR of 547 bp. The ChPDIA3 gene sequence has an ORF frame that is 1479 bp in length and encodes 492 amino acids. Analysis of the phylogenetic tree constructed by Neighbor Joining method showed that ChPDIA3 clustered with other shellfishes into a single unit, which was consistent with the law of species evolution.

Discussion: The highest expression of ChPDIA3 was detected in gill tissues of the C. hongkongensis using RT-qPCR, and significantly higher expression in V. harveyi and LPS infection than Poly(I:C) (P<0.05). This may indicate that ChPDIA3 is primarily involved in the immune response against bacterial infections in the C. hongkongensis. The binding sites of miR-126-x, miR-21-y and ChPDIA3 were detected using dual luciferase experiments, respectively. The results showed that both miR-126-x and miR-21-y inhibited the 3'-UTR region of ChPDIA3. This suggested that both miR-126-x and miR-21-y inhibited ChPDIA3 expression. This study will help to further understand the function of ChPDIA3 in response to pathogen infection, thus providing new ideas for understanding the resistance and adaptation of the C. hongkongensis to Vibrio infection.

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CRhvKP) poses a significant global health threat due to its enhanced virulence and resistance. This study analyzed 5,036 publicly available K. pneumoniae genomes from China (2005-2023), identifying 1,538 CRhvKP genomes, accounting for 44.6% of carbapenem-resistant isolates and 69.5% of hypervirulent isolates. Predominant carbapenemases included bla _KPC (92.1%), with an increasing prevalence of bla _NDM and bla _OXA-48-like genes. Most isolates (93.6%) carried both aerobactin and yersiniabactin genes. The genetic background showed high diversity, characterized by 36 sequence types (STs) and 22 capsule types, with high-risk endemic STs such as ST11, ST15, and ST23 being predominant. ST23 demonstrated enhanced virulence, whereas ST11 carried more resistance genes but showed minimal presence of iroBCDN genes. A core genome MLST analysis revealed that 89.0% of CRhvKP isolates clustered into 131 clonal groups, indicating widespread dissemination, particularly in eastern China. CR and hv plasmids, primarily IncF, IncH, and IncR types, showed distinct community structures, with CR plasmids demonstrating higher mobility and diversity. Crucially, we identified 40 CR-hv convergent plasmids across five STs, likely resulting from plasmid fusions, which have become increasingly prevalent in eastern China over the last decade. Furthermore, chromosomal integration of hv genes and bla _KPC-2 was detected, underscoring the stable inheritance of these traits. Class 1 Integrons were present in 84.5% of CRhvKP strains, most notably in ST11 and least in ST23. These integrons harbored genes that confer resistance to various antibiotics, including bla _IMP and bla _VIM, with their content varying across different STs. This study highlights the genetic complexity, rapid dissemination, and increasing prevalence of CRhvKP in China, emphasizing the urgent need for enhanced genomic surveillance and targeted interventions to mitigate the threat posed by these multidrug-resistant and hypervirulent strains.

Background: The epidemiological trend of lower respiratory tract fungal infections remains unclear. This study aims to quantify the global burden of these infections from 1990 to 2021 using data from the Global Burden of Disease Study 2021.

Methods: Data were analyzed at global, regional, and national levels, considering factors such as age, gender, region, and socio-demographic index (SDI). Key indicators included age-standardized disability-adjusted life-year (ASDR) and age-standardized mortality rates (ASMR).

Results: On a global scale, the burden of lower respiratory fungal infections decreased significantly from 1990 to 2021, with a decline in mortality rates. Regionally, substantial disparities were observed among the 21 geographic super-regions. Nationally, Argentina experienced the greatest increase in ASDR and ASMR, while Finland showed the largest decrease, with average annual percentage changes (AAPC) below -5 for both indicators. Sex-based analysis revealed a notably higher burden in males compared to females. ASDR and ASMR were negatively correlated with SDI in most regions.

Conclusion: Although the global burden of lower respiratory tract fungal infections has decreased, it remains a substantial public health issue, particularly in low-SDI regions. There is an urgent need to implement targeted preventive measures to address this ongoing challenge.

Background: Klebsiella pneumoniae is one of the most important opportunistic pathogens causing healthcare-associated and community-acquired infections worldwide. In recent years, the increase in antibiotic resistance and infections caused by hypervirulent K. pneumoniae poses great public health concerns. In this study, host-pathogen interactions of different K. pneumoniae strains of human and animal origins were analyzed in microbiological, cell-biological and immunological experiments.

Methods: In vitro infection experiments using representatives of different K. pneumoniae pathotypes and various epithelial and macrophage cell lines were executed analyzing adhesion, invasion and intracellular replication. Experimental conditions involved normoxia and hypoxia. Furthermore, survival and growth of further K. pneumoniae isolates expressing defined siderophores in blood (platelet concentrates, serum) was investigated. All experiments were done in triplicate and statistically significant differences were determined.

Results: Significant differences in adhesion and invasion capability, phagocytosis resistance and intracellular replication were measured between different K. pneumoniae pathotypes. Especially, ESBL-producing K. pneumoniae isolates demonstrated increased invasion in host cell lines and survival in macrophages. A strong cytotoxic effect on intestinal cells was observed for hypervirulent K. pneumoniae. The results from our investigations of the growth behavior of K. pneumoniae in platelets and serum showed that siderophores and/or an enlarged capsule are not essential factors for the proliferation of (hypervirulent) K. pneumoniae strains in blood components.

Conclusion: Our in vitro experiments revealed new insights into the host-pathogen interactions of K. pneumoniae strains representing different pathovars and clonal lineages in different infectious contexts and hosts. While a clear limitation of our study is the limited strain set used for both infection and as potential host, the results are a further step for a better understanding of the pathogenicity of K. pneumoniae and its properties essential for different stages of colonization and infection. When developed further, these results may offer novel approaches for future therapeutics including novel "anti-virulence strategies".

Ehrlichia chaffeensis (E. chaffeensis) has recently emerged as an intracellular bacterial pathogen with sophisticated survival mechanisms that include repurposing evolutionarily conserved eukaryotic cell signaling pathways for immune evasion. E. chaffeensis exploits four major developmental signaling pathways (Wnt, Notch, Hedgehog, and Hippo) using short linear motif (SLiM) ligand mimicry to initiate signaling cascades. Dysregulation of these major signaling pathways leading to unchecked cell survival is implicated in various diseases, most notably cancer. E. chaffeensis exploits Wnt, Notch, Hedgehog and Hippo signaling pathways to inhibit apoptosis and co-opt other cellular functions to promote infection. This review will explore the signaling pathways exploited during Ehrlichia infection and the new discoveries that have illuminated this interesting example of the cell signaling convergence in cellular infection and cancer biology.

Immortalized bovine neuronal cell lines provide a reliable in vitro model for studying interactions with bovine infectious pathogens that target the host nervous system. Although we previously established an immortalized fetal bovine brain-derived FBBC-1 cell line, there are currently no other bovine neuronal cell lines commonly available. In the present study, we developed a novel immortalized cell line, IKBM, derived from the adult bovine brainstem by transferring a SV40 large T antigen gene using lentiviral vectors, and compared its characteristics to the FBBC-1 cell line. As with FBBC-1 cells, IKBM cells extended neurite-like processes in response to agents that increase cytosolic cyclic AMP levels. A comprehensive analysis using RNA sequencing demonstrated that both cell lines potentially possess neural progenitor cell-like properties and differentiate into dopaminergic neuron-like cells after induction of the outgrowth of neurite-like processes. Unexpectedly, we found that the mRNAs of multiple immunomodulatory molecules were highly expressed in IKBM cells, but not in FBBC-1 cells. Although IKBM cells were susceptible to infection with arboviruses (Akabane and Chuzan viruses) that cause neurological symptoms in cattle, viral titers were lower in IKBM cell cultures than in hamster lung-derived HmLu-1 cell cultures, which are frequently used to isolate arboviruses. The reduced production of viruses in IKBM cell cultures may be related to the high expression of immunomodulatory molecules in these cells. Therefore, IKBM and FBBC-1 cell lines offer the opportunity to develop unique in vitro models of the bovine nervous system for the study of host-pathogen interactions based on their respective properties.