Emerging Microbes & Infections最新文献

Nipah virus (NiV) remains a persistent public-health threat in Bangladesh. The national sentinel surveillance system has operated since 2006, yet fatal infections that occur before assessment often go untested. We piloted a post-mortem surveillance component at three sentinel hospitals (December 2023-April 2024). Trained anthropologists obtained written informed consent from the next of kin. Oral swabs were collected non-invasively shortly after death and tested for NiV RNA by qRT-PCR at the national reference laboratory, using standard controls and established protocols. Specimens were handled in BSL-2 plus conditions on site and transported in liquid-nitrogen dry shippers per national SOPs. Where indicated by epidemiologic risk, shipments were prioritized for rapid testing. Of 246 deceased individuals screened, 10 met the suspected NiV case definition and were enrolled; all died after admission. One decedent tested NiV-positive (Ct value of 27.3), which activated same-day outbreak investigation by IEDCR's National Rapid Response Team. Contacts (close contacts and one same-source exposed individual) were traced and tested (RT-qPCR/IgM acutely; IgG at 6 weeks); no secondary cases were detected. Operational timelines (death → enrolment → collection → testing) demonstrated that post-mortem sampling and confirmation can be completed rapidly within routine hospital workflows. Post-mortem oral-swab testing is feasible, acceptable, and operationally compatible with Bangladesh's national surveillance system. While not intended to improve detection among living patients, this non-invasive approach closes a critical gap by identifying previously untested fatal infections and providing a trigger for timely public-health response. Scaling this approach across sentinel sites could strengthen early detection and outbreak control in NiV-affected regions.

The recent spillover of highly pathogenic influenza A/H5N1 (HPAI-H5N1) viruses to cattle, other mammals, and humans poses a major risk to animal and human health. Virus adaptation to new species highlights the need for effective vaccines for animals and humans. We recently developed a rabies virus-based H5 vaccine encoding the HPAI-H5 antigen and presenting it on the surface of the rabies virus particle. To test the immunogenicity and efficacy of the vaccine in eliciting systemic and mucosal immune response, we vaccinated mice intramuscularly or intranasally with either live or inactivated and adjuvanted vaccine. The vaccine elicited neutralizing antibodies against RABV and H5N1 Influenza virus and protected mice from a lethal challenge with PR8 recombinants reassorted with the HA of clade 1 (Viet Nam 1203) or clade 2.3.4.4b HPAI-H5N1 viruses, highlighting its potential use in mitigating the risk of HPAI-H5N1 pandemic.

The emergence of multidrug-resistant Klebsiella pneumoniae poses a significant challenge to clinical treatment and public health. Strategies combining antibiotics with FDA-approved non-antibiotic drugs have recently attracted attention as a promising approach to overcome antibiotic resistance. In this study, we systematically evaluated the synergistic effect of the antihistamine loratadine in combination with colistin against K. pneumoniae. Our results demonstrate that loratadine significantly restores the bactericidal activity of colistin against colistin-resistant K. pneumoniae both in vitro and in vivo, without increasing toxicity, while also delaying the development of colistin resistance. Mechanistic investigations using fluorescence-based assays and proteomic analysis revealed that loratadine acts as a potent adjuvant for colistin, effectively restoring its activity against colistin-resistant K. pneumoniae by interfering with lipid A modification. This phenomenon is further supported by the downregulation of lipid A-modifying enzyme-related protein EptB. In addition, the combination of loratadine and colistin disrupts the double-layer membrane barrier, leading to proton motive force (PMF) dysregulation, reduced intracellular ATP levels, and impaired efflux pump activity. Collectively, this study highlights the potential of drug repurposing as an effective strategy to combat antimicrobial resistance and provides a foundation for the development of combination therapies against multidrug-resistant pathogens.

The persistent emergence of SARS-CoV-2 variants continues to compromise current vaccine efficacy, driving the development of broad-spectrum coronavirus vaccines to address variant evasion and future outbreaks. To develop a pan-coronavirus vaccine, we identified some conserved T/B epitopes across spike proteins of human-infecting coronaviruses, focusing on two conserved long peptides, VV and VS, which demonstrated broad immunogenicity in PBMCs from COVID-19 convalescent patients. By structurally fusing the VV and VS long peptides with heptad repeat 1/2 (HR1/2) domains from the S2 subunit, we engineered a trimeric immunogen HR1-VV-HR2-VS. This design induced superior cellular and humoral immune responses compared to individual peptide components in immunized mice. The vaccine also significantly reduced viral loads and attenuated lung pathology in mice challenged with HCoV-229E, SARS-CoV-2 prototype strain, and the KP.2 variant, demonstrating cross-protective immunity. Therefore, these results indicated that HR1-VV-HR2-VS vaccine elicits cross-protective immunity, highlighting its potential as a universal coronavirus vaccine. In addition, we developed an innovative peptide vaccine platform based on the HR1-HR2 trimeric structural protein, which serves as a potent polypeptide fusion scaffold to significantly enhance peptide immunogenicity.

Extensively drug-resistant gram-negative bacteria harbouring dual resistance to carbapenems and colistin represent a critical global health threat. A total of 929 population-representative Enterobacter isolates were systematically collected from 29 hospitals across four regions of Taiwan between 2010 and 2020. Forty-one isolates (4.4%) were nonsusceptible to carbapenems and underwent whole-genome sequencing, resistance gene profiling, plasmid analysis, and antimicrobial susceptibility testing (AST). Among them, 35 isolates (85.4%) exhibited dual resistance to carbapenems and colistin; however, only half (17/35) were detectable by standard phenotypic AST. Colistin resistance was primarily mediated by activation of the chromosomal arnBCADTEF operon, which was frequently inducible and often undetected by standard testing, rather than by mcr-9 or mcr-10. A conserved IncHI2 plasmid carrying bla_IMP-8 and mcr-9 persisted and circulated across Enterobacter species for over a decade. Species-specific resistance patterns were observed: E. roggenkampii typically exhibited colistin resistance despite lacking carbapenemases, whereas E. hormaechei commonly carried bla_IMP-8 and occasionally lacked the arn operon. Both species exhibited comparable imipenem nonsusceptibility, complicating therapeutic decision-making. The convergence of carbapenem and colistin resistance in a substantial proportion of Enterobacter isolates at the population level makes this genus an emerging priority for hospital infection control and antimicrobial resistance surveillance. These findings underscore the urgent need for improved diagnostics, strengthened antimicrobial resistance surveillance, and optimized treatment strategies.

Bordetella bronchiseptica, long regarded as a veterinary pathogen, is now emerging as a zoonotic threat to humans, particularly in immunocompromised individuals. We report a sentinel event involving a synchronized B. bronchiseptica outbreak in swine and their human caretaker, providing a unique opportunity to examine cross-species transmission and adaptation at the genomic level. Comparative genomics revealed that the human-adapted isolate (RL57) and its swine progenitor (XX35) share an identical chromosome, with XX35 harbouring an extra conjugative plasmid. Remarkably, RL57 did not simply lose this plasmid; instead, the entire plasmid was integrated into the chromosome via site-specific recombination. This integration allowed permanent retention of plasmid-encoded virulence and fitness genes, after which the plasmid was discarded to eliminate its replicative burden - a "capture-and-discard" mechanism of evolution. Following plasmid loss, the RL57 strain exhibited hypervirulence, faster growth, enhanced thermotolerance, and increased biofilm formation, indicating successful adaptation to the human host. Plasmid loss paradoxically rewired bacterial metabolism: sulfur assimilation and sulfonate utilization pathways were upregulated to fuel host adaptation. Strikingly, despite a collapse in transcription of specific metabolic modules, translational compensation maintained high protein levels, driving robust biofilm formation and thermal tolerance. These findings reveal a previously unrecognized evolutionary strategy in which plasmid integration followed by subsequent plasmid loss amplifies pathogenicity and host adaptability. Finally, we propose a One Health surveillance triad - metagenomic tracking of plasmid-chromosome dynamics, recombination hotspot screening, and metabolic shift monitoring - to proactively identify and mitigate such zoonotic events.

Type I interferons (IFN-I) are essential for antiviral immunity, and precise regulation of IFN-I production is crucial to balance viral clearance and immunopathology. Here, we demonstrate that the interferon-stimulated gene TOR3A negatively regulates type I IFN signalling during respiratory syncytial virus (RSV) infection. TOR3A expression was upregulated in macrophages and RSV-infected patients, and its deficiency enhanced antiviral responses, leading to reduced viral load. Mechanistically, RSV infection induced TOR3A expression through the IFN-STAT1 pathway, which in turn suppressed IFN-I production. Furthermore, TOR3A recruited the E3 ubiquitin ligase STUB1 to mediate K48-linked ubiquitination and proteasomal degradation of RIG-I at lysine 146, thereby promoting RSV immune evasion. Our study identifies TOR3A as a novel suppressor of antiviral immunity and uncovers a mechanism by which RSV exploits host ISGs to dampen IFN-I responses, providing new insights into viral pathogenesis and potential therapeutic strategies.

Multiple mechanisms underpinning biofilm antimicrobial resistance (AMR) have been studied individually. This study aimed to integrate these mechanisms, to understand their contributions to staphylococcal biofilm AMR, as a part of a whole, and to elucidate key hurdles hindering effective biofilm eradication by antimicrobial agents. Nine antibiotics were selected against microplate-based biofilms formed by Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis RP62A. Four mechanisms, including repressed bacterial metabolism, the barrier effect of the biofilm extracellular polymeric substances (EPS) matrix, the acidic inner-biofilm pH, and inoculum effects associated with high-cell-density biofilm growth were studied. The impact of individual mechanism on biofilm AMR was quantitated by determining the fold increase of concentration that allows antibiotics to overcome the mechanism. Antibiotic concentrations were then incrementally increased from minimum bactericidal concentration (MBC) to sequentially address all four mechanisms, ultimately aiming to kill at least 99.9% of biofilm cells. A simplified method was developed to evaluate the dependence of antibiotics on bacterial metabolic states for the lethality. Gentamicin, tobramycin and ciprofloxacin at 1024 µg/mL overcame all four mechanisms and successfully killed S. aureus ATCC 25923 biofilms by at least 3 log units. Ciprofloxacin at 1024 µg/mL effectively killed S. epidermidis RP62A biofilms. The contribution of each mechanism to biofilm AMR was strain- and drug-dependent, with low-cell metabolism being the most important factor. This study underscores the individual contributions of each mechanism to staphylococcal biofilm AMR and highlights the necessity of targeting all four mechanisms to achieve effective biofilm eradication.

The 2022 global outbreak of the monkeypox virus (MPXV) clade IIb highlighted changes in transmission dynamics, clinical features, and tissue tropism, yet the impact of host cell origin on viral transcription remains unclear. We performed comparative transcriptomic profiling of MPXV clade IIb in human epithelial cell lines from vaginal, intestinal, ectocervical, and renal tissues. Temporal analysis in vaginal cells revealed two major transcriptional clusters: early genes enriched for host-virus interaction factors in terminal genome regions, and intermediate-late genes encoding transcription, replication, and morphogenesis functions in the core genome. Some genes were expressed at each time point and comprised transcripts encoding signal transduction and inflammation-modulating factors. Single-time point comparisons linked higher viral particle production in vaginal and intestinal cells to intermediate-late gene enrichment, whereas ectocervical and renal cells favoured host-virus interaction transcripts. Several genes, including those that modulate signal transduction pathways, were highly expressed across different cell types. These findings reveal cell-type-dependent modulation of MPXV transcription and identify conserved and variable viral factors that may inform antiviral strategies.

The twenty-first century has seen global surges in scarlet fever and invasive Group A Streptococcus (GAS) infections, partly driven by the emergence of the toxigenic M1_UK lineage. Characterized by increased SpeA superantigen expression and the stepwise accumulation of 27 single nucleotide polymorphisms (SNPs), M1_UK has become the dominant GAS emm1 lineage in Europe, Australia and Canada, representing a notable shift in GAS molecular epidemiology. Interestingly, other distinct emm1 variants have emerged in China and Denmark but are yet to expand globally in the same manner. This review examines the recent evolution of the GAS emm1 lineage, with emphasis on genomic and molecular drivers, highlighting the ongoing diversification of this pathogen and the need for continued surveillance and research.