Emerging Microbes & Infections最新文献

In 2018, a single detection of a novel reassortant swine influenza A virus (swIAV) was made in Denmark. The hemagglutinin (HA) of the virus was from the H1N1 pandemic 2009 (H1N1pdm09) lineage and the neuraminidase (NA) from the H1N1 Eurasian avian-like swine lineage (H1N1av). By 2022, the novel reassortant virus (H1pdm09N1av) constituted 27% of swIAVs identified through the Danish passive swIAV surveillance program. Sequencing detected two H1pdm09N1av genotypes; Genotype 1 contained an entire internal gene cassette of H1N1pdm09 origin, Genotype 2 differed by carrying an NS gene segment of H1N1av origin. The internal gene cassette of Genotype 2 became increasingly dominant, not only in the H1pdm09N1av population, but also in other Danish enzootic swIAV subtypes. Phylogenetic analysis of the HA genes from H1pdm09N1av viruses revealed a monophyletic source, a higher substitution rate compared to other H1N1pdm09 viruses and genetic differences with human seasonal and other swine adapted H1N1pdm09 viruses. Correspondingly, H1pdm09N1av viruses were antigenically distinct from human H1N1pdm09 vaccine viruses. Both H1pdm09N1av genotypes transmitted between ferrets by direct contact, but only Genotype 1 was capable of efficient aerosol transmission. The rapid spread of H1pdm09N1av viruses in Danish swine herds is concerning for swine and human health. Their zoonotic threat is highlighted by the limited pre-existing immunity observed in the human population, aerosol transmission in ferrets and the finding that the internal gene cassette of Genotype 2 was present in the first two zoonotic influenza infections ever detected in Denmark.

The emergence of carbapenem-resistant Escherichia coli (CREC) poses crucial challenges in clinical management, requiring continuous monitoring to inform control and treatment strategies. This study aimed to investigate the genomic and epidemiological characteristics of CREC isolates obtained from a tertiary hospital in China between 2015 and 2022. Next-generation sequencing was used for genomic profiling, and clinical data from patients were integrated into the analysis. ST405 (21.2%), ST167 (20.3%) and ST410 (15.9%) were the most prevalent of the 30 distinct sequence types (STs) identified among the 113 unique CREC isolates. Infections caused by the ST405 CREC clone and severe underlying diseases were associated with higher in-hospital mortality rates, particularly in patients aged ≥65 years. Furthermore, the ST405 clone exhibited a greater number of virulence and resistance genes than non-ST405 CREC clones. The virulence gene eaeX and resistance genes mph(E) and msr(E) were exclusively found in ST405 clones, while other virulence genes (agn43, ipad and malX) and resistance genes (armA, catB3 and arr-3) were more prevalent in this clones. Additionally, ST405 showed higher minimum inhibitory concentrations for both meropenem and imipenem and showed superior growth under the meropenem challenge. Galleria mellonella virulence assays revealed that the ST405 CREC clone was more virulent than other predominant CREC STs. Our findings underscore the clinical threat posed by the ST405 CREC clone, which exhibits both enhanced virulence and extensive drug resistance. These results highlight the urgent need for stringent surveillance and targeted interventions to curb its further dissemination and prevent potential outbreaks.

Marburg virus disease (MVD) is a severe infectious disease caused by the Marburg virus (MARV), posing a significant threat to humans. MARV needs to be operated under strict biosafety Level 4 (BSL-4) laboratory conditions. Therefore, accessible and practical animal models are urgently needed to advance prophylactic and therapeutic strategies for MARV. In this study, we constructed a recombinant vesicular stomatitis virus (VSV) expressing the Marburg virus glycoprotein (VSV-MARV/GP). Syrian hamsters infected with VSV-MARV/GP presented symptoms such as thrombocytopenia, lymphopenia, haemophilia, and multiorgan failure, developing a severe systemic disease akin to that observed in human MARV patients. Notably, the pathogenicity was found to be species-specific, age-related, sex-associated, and challenge route-dependent. Subsequently, the therapeutic efficacy of the MR191 monoclonal antibody was validated in this model. In summary, this alternative model is an effective tool for rapidly screening medical countermeasures against MARV GP in vivo under BSL-2 conditions.

Congenital Zika virus (ZIKV) infection significantly affects neurological development in infants and subsequently induces neurodevelopmental abnormality symptoms; however, the potential mechanism is still unknown. Therefore, in order to effectively intervene in neurodevelopmental abnormalities in infected infants, it is necessary to identify the main brain regions affected by congenital infection. In this study, we constructed a congenital ZIKV-infected murine model using immunocompetent human STAT2 knock-in mice, which presented long-term neurodevelopmental abnormalities with abnormal neurodevelopmental symptoms. We found that the hippocampus, which regulates cognitive behaviour and processes spatial information and navigation, was the main brain region affected by congenital infection and that hippocampal cells were more prone to autophagy during the growth period of these mice at the transcriptional and pathological levels. These findings highlighted that congenital ZIKV infection could interrupt hippocampal function by activating autophagy, thus providing a theoretical basis for the clinical treatment of congenital ZIKV-infected infants.

The newly emerged avian influenza A H5N1 Clade 2.3.4.4b can infect dairy cows and shed live virus in their milk. Sporadic cattle-to-human infections have been reported, highlighting the urgent need to understand its pathogenesis in mammals. Using both non-lactating and lactating BALB/c mice, we examined the viral tissue tropism, histopathological damages, and host immune responses upon intranasal inoculation with a reverse-genetic virus constructed based on A/dairy cattle/Texas/24-008749-003/2024 (Cattle-H5N1) and comparing with an older reference Clade 1 virus, A/Vietnam/1194/2004 virus (VNM1194-H5N1). Cattle-H5N1 was highly lethal in mice (mLD₅₀ = 1.48PFU) with broad tissue tropism and produced higher titer in respiratory tissue and multiple extrapulmonary organs than VNM1194-H5N1. In the lungs, Cattle-H5N1 infection of airway epithelium, type II pneumocytes and CD45⁺ immune cells were at a higher frequency than those of VNM1194-H5N1-infected mice, resulting in severe epithelial destruction and diffuse alveolar damage accompanied by elevated lung and serum pro-inflammatory cytokine/chemokines. Although both H5N1 viruses showed lactating mammary gland tropism, the gland tissue was more severely damaged after Cattle-H5N1 infection with abundant viral antigens expression in glandular cells, associated fat and lymphoid tissues. Furthermore, more suckling mice co-housed with Cattle-H5N1 infected lactating mice were virus-positive (7/30 pups) than VNM1194-H5N1. Brains were heavily infected by Cattle-H5N1, and neurological signs such as body-rolling/spinning, trembling and/or limb paralysis were seen only in Cattle-H5N1 infected mice. The spleen was more severely damaged by Cattle-H5N1 infection, which showed massive viral antigen expression accompanied by severe apoptosis and splenic atrophy, concluding that Cattle-H5N1 is more virulent in mice than VNM1194-H5N1.

Insertion sequences (IS) represent mobile genetic elements that have been shown to be associated with bacterial evolution and adaptation due to their effects on genome plasticity. In Bordetella pertussis, the causative agent of whooping cough, the numerous IS elements induce genomic rearrangements and contribute to the diversity of the global B. pertussis population. Previously, we have shown that the majority of IS-specific endogenous promoters induce the synthesis of alternative transcripts and thereby affect the transcriptional landscape of B. pertussis. Here, we describe the regulatory RNA Rfi2, which is transcribed from the P_out promoter of the IS481 gene BP1118 antisense to the adjacent fim2 gene encoding the major serotype 2 fimbrial subunit of B. pertussis. Among the classical bordetellae, Rfi2 is unique to B. pertussis, suggesting its specific role in virulence. We show that Rfi2 RNA attenuates fim2 transcription and, consequently, the production of the Fim2 protein. Interestingly, the mutant that does not produce Rfi2 displayed significantly increased cytotoxicity towards human macrophages compared to the parental strain. This observation suggests that the Rfi2-mediated reduction in cytotoxicity represents an evolutionary adaptation of B. pertussis that fine-tunes its interaction with the human host. Given the immunogenicity of Fim2, we further hypothesize that Rfi2-mediated modulation of Fim2 production contributes to immune evasion. To our knowledge, Rfi2 represents the first functionally characterized IS element-driven antisense RNA that modulates the expression of a virulence gene.

Coronaviruses (CoVs) pose a significant threat to public health, causing a wide spectrum of clinical manifestations and outcomes. Beyond precipitating global outbreaks, Human CoVs (HCoVs) are frequently found among patients with respiratory infections. To date, limited attention has been directed towards alphacoronaviruses due to their low prevalence and fatality rates. Nasal swab and serum samples were collected from a paediatric patient, and an epidemiological survey was conducted. Retrospective surveillance investigated the molecular prevalence of CoV in 880 rodents collected in the Republic of Korea (ROK) from 2018 to 2022. Next-generation sequencing (NGS) and phylogenetic analyses characterized the novel HCoV and closely related CoVs harboured by Apodemus spp. On 15 December 2022, a 103-day-old infant was admitted with fever, cough, sputum production, and rhinorrhea, diagnosed with human parainfluenza virus 1 (HPIV-1) and rhinovirus co-infection. Elevated AST/ALT levels indicated transient liver dysfunction on the fourth day of hospitalization. Metagenomic NGS (mNGS) identified a novel HCoV in nasal swab and serum samples. Retrospective rodent surveillance and phylogenetic analyses showed the novel HCoV was closely related to alphacoronaviruses carried by Apodemus spp. in the ROK and China. This case highlights the potential of mNGS to identify emerging pathogens and raises awareness of possible extra-respiratory manifestations, such as transient liver dysfunction, associated with novel HCoVs. While the liver injury in this case may be attributable to the novel HCoV, further research is necessary to elucidate its clinical significance, epidemiological prevalence, and zoonotic origins.

During our surveillance of avian influenza viruses (AIVs) in wild birds across China, H10Nx viruses were isolated from diverse migratory flyways between 2022 and 2024. We identified one wild-bird H10N5 strain that shared a common ancestor with the human H10N5 virus in multiple gene segments. Phylogenetic and molecular dating revealed the origin and evolution of H10N5, highlighting the need for continued monitoring.

Antimicrobial resistance has recently increased due to emerging carbapenem-resistant Klebsiella pneumoniae and extended-spectrum β-lactamase (ESBL)-producing strains of K. pneumoniae, especially among hypermucoviscous K. pneumoniae (hmKp) strains. To evaluate the prevalence of ESBL-producing and carbapenem-resistant strains in hmKp and non-hmKp clinical isolates through a systematic review and meta-analysis. We searched PubMed, Scopus, and Cochrane Library databases from January 2000 to June 2023. Clinical and in vivo/in vitro studies involving confirmed K. pneumoniae clinical isolates differentiated into hmKP and non-hmKP strains based on string test results. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on the number of individuals in each target group. Forest plots were used to visualize the effect sizes and 95% CIs of individual studies estimated using the inverse variance and DerSimonian - Laird methods with fixed - and random-effects models, respectively. Heterogeneity was assessed using Cochran's Q test (I² ≥ 50%). Fifteen studies comprising 2049 clinical isolates of K. pneumoniae met the inclusion criteria. Meta-analysis revealed that hmKp strains were associated with a significantly lower prevalence of ESBL-producing strains (pooled OR: 0.26, 95% CI: 0.11-0.63, P = 0.003) and a slightly lower prevalence of carbapenem-resistant strains than non-hmKp strains (pooled OR: 0.63, 95% CI: 0.40-0.97, P = 0.038). hmKp strains exhibited lower and slightly lower prevalence of ESBL production and carbapenem resistance, respectively, than non-hmKp strains. However, given the rising prevalence of ESBL-producing and carbapenem-resistant hmKp strains, patients infected by string-test-positive K. pneumoniae must be managed prudently, considering the potential for highly resistant strains.