Emerging Microbes & Infections最新文献

ABSTRACTThe ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. - are designated by the World Health Organization as critical-priority multidrug-resistant organisms. These bacteria are leading contributors to the global antimicrobial resistance crisis, significantly increasing morbidity, mortality, and healthcare costs worldwide. Their capacity to evade conventional antibiotics continues to complicate clinical management and undermine infection control efforts. Tackling the global threat of ESKAPE pathogens demands coordinated and sustained interventions. This mini review summarizes recent evidence on the burden and prevalence of ESKAPE infections and assesses emerging strategies to combat resistance. Progress in surveillance and promising preclinical and clinical studies of novel therapies underscore that integrated approaches are crucial. Moving forward, a balanced emphasis on prevention, surveillance, and therapeutic innovation will be essential to mitigating the threat posed by ESKAPE pathogens over the coming decade.

Seasonal influenza A viruses evolve rapidly, yet the emergence and molecular basis of resistance to the polymerase acidic (PA) inhibitor baloxavir marboxil (BXM), which is widely used in China, remain elusive. To address this, 3938 PA gene sequences were collected from influenza patients across mainland China between 2018 and 2025, from the national surveillance network and GISAID. By screening post-market mutations in the N-terminal domain of PA (PAN) that appeared in at least two samples and at a frequency below 50%, twenty-five single-point mutations were identified and additionally six linked mutations potentially associated with drug pressure. The impact of these mutations on BXM sensitivity was subsequently evaluated. Our analysis revealed the emergence of known mutations associated with reduced BXM sensitivity, including L28P, K34R, E198 K, although their prevalence remained low (2/3850, 0.05%). Notably, we identified a novel substitution, D27G, which conferred an approximately 12.4-fold reduction in BXM susceptibility compared with the wild-type virus and exhibited higher replication fitness than the canonical resistance mutation I38T, as demonstrated in human airway organoids. Molecular dynamics simulations further indicated that PA-D27G attenuates the interaction between PA and baloxavir acid, the active form of BXM. Epidemiological analysis showed that D27G mutation remained rare, being detected in four isolates (4/1247, 0.32%) in mainland China, and at a sporadic prevalence (<0.1%, 9/53132) across global isolates. In conclusion, these results demonstrate the early emergence of BXM-associated resistance in China and identify PA-D27G as a resistance-associated mutation with preserved viral fitness, underscoring the importance of continued genomic and epidemiologic surveillance.

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 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.

The H1N1pdm09 influenza virus, which emerged in 2009 following a unique reassortment of swine-origin gene segments, rapidly replaced the seasonal H1N1 strain and triggered the first influenza pandemic of the twenty-first century. In Brazil, the virus initially spread through intense community transmission before establishing a pattern of seasonal circulation. However, its long-term evolutionary dynamics in the country remain insufficiently characterized. To address this gap, we conducted a coordinated national genomic surveillance effort focused on the period from 2014 onward, when Brazil began systematic whole-genome sequencing of circulating H1N1pdm09 viruses. Through collaborative sequencing across all five Brazilian macroregions, we generated 597 complete genomes collected between 2014 and 2024. Using phylodynamic approaches, we reconstructed the spatiotemporal spread of H1N1pdm09, identified major circulating lineages, and integrated epidemiological data to assess patterns of persistence and regional transmission. Our findings reveal sustained circulation and multiple independent viral introductions over the past decade, with evidence of localized lineage maintenance, particularly in the Southeast and South regions. Phylogenetic analyses also indicate repeated seeding from international sources, underscoring the continued impact of global viral movement. In addition, genome-wide comparisons revealed reassortment events involving internal segments, which may have contributed to the persistence and adaptation of dominant lineages following the COVID-19 pandemic. This study presents the most comprehensive reconstruction of H1N1pdm09 evolutionary dynamics in Brazil to date, highlighting the critical role of integrated, nationwide genomic surveillance in enhancing public health preparedness in tropical and subtropical regions.

Dengue, transmitted by Aedes mosquitoes, can progress to severe symptoms like hemorrhagic fever and shock syndrome. While the virus and host immune response contribute to severity, other factors, such as small extracellular vesicles (sEVs), may play a role. sEVs mediate intercellular communication by transferring cellular components; however, their role in vivo infection remains unclear. We isolated and characterized sEVs from DENV-infected C6/36 mosquito cells, finding that they interact with mammalian cells and internalize the content. Using sEVs populations (with a size between 100 and 200 nm), we demonstrated enhanced infection in in vitro and in vivo murine models, including immunocompetent and immunosuppressed mice, which developed severe dengue-like symptoms. Our study reveals that sEVs from DENV-infected mosquito cells contribute to dengue pathogenesis, inducing severe symptoms in in vivo models, highlighting their potential role in disease progression and severe outcomes.

Multiple influenza virus subtypes actively circulate in nature, and assessing their transmissibility provides crucial information for predicting their pandemic potential and for pandemic preparedness. Here, we evaluated the receptor-binding preferences, replication, and transmission of five different influenza viruses (i.e., CA/07-H1N1, GX/18-H1N1, CK/S2283-H3N8, CK/SD007-H9N2, and DK/35-H5N1) in Syrian hamsters. Receptor-binding analysis using biolayer interferometry revealed that four of these viruses preferentially bound α2,6-linked sialic acid receptors, whereas the H5N1 virus bound to α2,3-linked and α2,6-linked sialic acid receptors similarly. All five viruses replicated well in the respiratory tissues of Syrian hamsters, but did not cause obvious symptoms or death, indicating that Syrian hamsters can tolerate influenza virus infection and are not suitable for influenza virus pathogenicity studies. The four viruses that bound to α2,6-linked sialic acid receptors with higher affinity than to α2,3-linked sialic acid receptors were transmissible between Syrian hamsters via direct contact or respiratory droplets; however, the H5N1 virus was not transmissible through respiratory droplets, consistent with previously reported transmission characteristics observed for these viruses in guinea pigs and ferrets. Given that Syrian hamsters and humans have similar receptor expression patterns in their nasal mucosa, our findings suggests that Syrian hamsters can be used as a suitable animal model for evaluating the transmissibility of influenza viruses that preferentially bind to α2,6-linked sialic acid receptors.

Linezolid-resistant Clostridioides difficile, conferred by the acquisition of cfr-like genes, has been reported in Europe and America. However, the emergence of linezolid resistance in C. difficile in the Asia-Pacific region and its impacts on C. difficile pathogenicity remain unclear. In this study, 881 C. difficile isolates from the Asia-Pacific region were screened for cfr-like genes. Whole genome sequencing was performed on 16 cfr-like gene-positive isolates from four countries. Thirteen isolates possessed cfr(B), which was located within Tn6218, while three isolates possessed cfr(C), which was located within the integrative and conjugative elements (ICE) F548 and DA275. Fourteen (87.5%, 14/16) of the cfr-like gene-positive isolates were resistant to linezolid. In comparison to the two isolates susceptible to linezolid, these 14 isolates exhibited significantly higher mRNA expression levels of cfr(B) and cfr(C), along with significantly higher bacterial density at 12 h. Conversely, they demonstrated reduced abilities for sporulation and biofilm formation. After the cfr(B) gene was knocked down by the CRISPR interference, the C. difficile strain presented lower bacterial density at 12 h, higher toxin production and stronger sporulation and biofilm formation abilities. Our findings reveal the emergence of cfr-like genes C. difficile isolates in the Asia-Pacific region, highlighting that cfr-like genes not only mediate linezolid resistance but also contribute to regulating pathogenic potential. Linezolid resistance in CDI should be closely monitored in specific patients.