Emerging Microbes & Infections最新文献

The tRNA-derived small RNAs (tsRNAs) are a new class of non coding RNAs, which are stable in body fluids and can be used as potential biomarkers for disease diagnosis. However, the exact value of tsRNAs in the diagnosis of tuberculosis (TB) is still unclear. The objective of the present study was to evaluate the performance of the serum tsRNAs biosignature to distinguish between active TB, healthy controls, latent TB infection, and other respiratory diseases. The differential expression profiles of tsRNAs in serum from active TB patients and healthy controls were analyzed by high-throughput sequencing. A total of 905 subjects were prospectively recruited for our study from three different cohorts. Levels of tsRNA-Gly-CCC-2, tsRNA-Gly-GCC-1, and tsRNA-Lys-CTT-2-M2 were significantly elevated in the serum of TB patients compared to non-TB individuals, showing a correlation with lung injury severity and acid-fast bacilli grades in TB patients. The accuracy of the three-tsRNA biosignature for TB diagnosis was evaluated in the training (n = 289), test (n = 124), and prediction (n = 292) groups. By utilizing cross-validation with a random forest algorithm approach, the training cohort achieved a sensitivity of 100% and specificity of 100%. The test cohort exhibited a sensitivity of 75.8% and a specificity of 91.2%. Within the prediction group, the sensitivity and specificity were 73.1% and 92.5%, respectively. The three-tsRNA biosignature generally decreased within 3 months of treatment and then remained stable. In conclusion, the three-tsRNA biosignature might serve as biomarker to diagnose TB and to monitor the effectiveness of treatment in a high-burden TB clinical setting.

To unravel distinct patterns of metagenomic surveillance and respiratory microbiota between Mycoplasma pneumoniae (M. pneumoniae) P1-1 and P1-2 and to explore the impact of the COVID-19 pandemic on epidemiological features, we conducted a multicentre retrospective study which spanned 90,886 pneumonia patients, among which 3164 cases M. pneumoniae were identified. Our findings revealed a concurrent outbreak of M. pneumoniae, with the positivity rate rising sharply to 9.62% from July 2023, compared to the 0.16% to 4.06% positivity rate observed during the 2020-2022 COVID-19 pandemic. P1-1 had a higher odds ratio of co-detecting opportunistic pathogens. However, no significant differences were observed in the co-detection odds ratio between children and other age groups in P1-2. This study is the first to demonstrate differences in relative abundance, diversity of respiratory microbiota and co-detection rate of opportunistic pathogen between M. pneumoniae P1-1 and P1-2. Through bronchoalveolar lavage (BAL) metagenomic and host transcriptomic analyses, we identified variations in co-detection rates of M. pneumoniae P1-1 genotype with opportunistic pathogens like S. pneumoniae, alterations in respiratory microbiota composition, lung inflammation, and disruption of ciliary function. Consistent with the results of host transcriptome, we found that P1-1 infections were associated with significantly higher rates of requiring respiratory support and mechanical ventilation compared to P1-2 infections (Fisher's exact test, p-value = 0.035/0.004). Our study provides preliminary evidence of clinical severity between M. pneumoniae strains, underscoring the need for ongoing research and development of targeted therapeutic strategies.

Since early 2024, highly pathogenic avian influenza H5N1 viruses have been causing outbreaks in dairy cattle in the United States. Here, we compared the replicative capacity of A/dairy cattle/Texas/24-008749-001/2024 (H5N1; Cow-H5N1) isolated from a dairy cow, A/chicken/Ghana/AVL-76321VIR7050-39/2021 (H5N1; Chicken-H5N1) isolated from a chicken, and a human H1N1 2009 pandemic virus in ex vivo explant cultures of mammary gland and teat from lactating cows. We also examined the expression of influenza virus receptors in these organs. We observed that human influenza virus receptors are widely distributed throughout the epithelium of alveoli, ducts, and gland cisterns within the mammary gland, and in the teat cistern epithelium of dairy cattle, whereas avian influenza virus receptors are distributed on the alveolar, ductal, and teat cistern epithelium. We also found that Cow-H5N1 virus replicates more efficiently than Chicken-H5N1 or human H1N1pdm viruses in the gland cistern epithelium of dairy cattle. Notably, bovine H5N1 viruses replicated efficiently in the epithelium of the bovine teat cistern. These findings suggest that H5N1 viruses invade the mammary gland through the teat canal, which is easily accessed by viruses.

Understanding SARS-CoV-2 epidemiology in companion animals is critical for evaluating their role in viral transmission and their potential as sentinels for human infections. This large-scale serosurvey analyzed serum samples from 706 cats and 2,396 dogs collected across the USA in 2023 using a surrogate virus neutralization test (sVNT) to detect SARS-CoV-2 antibodies. Overall, 5.7% of cats and 4.7% of dogs tested positive for antibodies, with younger animals (under 12 months) showing significantly lower seropositivity rates (p = 0.0048). Additionally, we analyzed 153 positive samples for variant-specific antibody responses using six sVNT kits targeting the Delta variant and five Omicron sublineages. Among cats, 67.5% showed antibodies to Delta, with positivity rates for Omicron sublineages as follows: BA.1 (62.5%), BA.2 (42.5%), BA.4/BA.5 (77.5%), XBB (52.5%), and XBB.1.5 (45.0%). In dogs, 55.8% were positive for Delta, and Omicron sublineage rates were BA.1 (46.0%), BA.4/BA.5 (37.2%), XBB (58.4%), BA.2 (13.3%), and XBB.1.5 (9.7%). Given the close contact between companion animals and humans, and the persistence of antibodies against various SARS-CoV-2 variants and sublineages, our findings suggest that seroprevalence in cats and dogs may serve as valuable tool for tracking COVID-19 epidemiology.

Plasmodium malariae, a causative agent of quartan malaria, is prevalent across tropical and subtropical regions, but global cases have been usually very rare and sporadic. However, a significant outbreak of quartan malaria caused by P. malariae occurred in Khanh Vinh District, Khanh Hoa Province, Vietnam in 2023 and the outbreak persists. In this report, we present the epidemiological and clinical characteristics of this unprecedented outbreak of quartan malaria in Vietnam.

ABSTRACTAvian influenza active surveillance was conducted in Bangladesh from January 2022 to November 2023 in live-poultry markets (LPMs) and Tanguar Haor wetlands. The predominant viruses circulating in LPMs were low pathogenic avian influenza (LPAI) A(H9N2) and clade 2.3.2.1a highly pathogenic avian influenza (HPAI) A(H5N1) viruses. Non-H9N2 LPAIs were found at Tanguar Haor and at a lower prevalence in LPMs. Starting from June 2023, we detected novel genotypes of clade 2.3.4.4b A(H5N1) viruses from ducks in LPMs. The HA, NA, and M genes of these viruses are related to those of 2020 European clade 2.3.4.4b H5N1 viruses such as A/Eurasian Wigeon/Netherlands/1/2020 (Netherlands/1). However, analyses of the other five gene segments' sequences identified three distinct genotypes (BD-G2, BD-G3, and BD-G4). BD-G2 viruses were closely related to the clade 2.3.4.4b H5N1 viruses that have been detected in Japan and nearby regions since November 2022. BD-G3 viruses were reassortants, with gene segments from other Eurasian LPAI viruses. BD-G4 viruses were similar to BD-G2 viruses, but their NS gene was accrued from contemporary Bangladeshi clade 2.3.2.1a A(H5N1) viruses. The ability of any of the clade 2.3.4.4b viruses to displace the long-entrenched 2.3.2.1a A(H5N1) viruses in Bangladesh is unknown.

Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) has caused a panzootic affecting all continents except Australia, expanding its host range to several mammalian species. In March 2024, H5N1 HPAIV was first detected in dairy cattle and goats in the United States. Over 891 dairy farms across 16 states have tested positive until 25 December 2024, with zoonotic infections reported among dairy workers. This raises concerns about the virus undergoing evolutionary changes in cattle that could enhance its zoonotic potential. The Influenza glycoprotein haemagglutinin (HA) facilitates entry into host cells through receptor binding and pH-induced fusion with cellular membranes. Adaptive changes in HA modulate virus-host cell interactions. This study compared the HA genes of cattle and goat H5N1 viruses with the dominant avian-origin clade 2.3.4.4b H5N1 in the United Kingdom, focusing on receptor binding, pH fusion, and thermostability. All the tested H5N1 viruses showed binding exclusively to avian-like receptors, with a pH fusion of 5.9, outside the pH range associated with efficient human airborne transmissibility (pH 5.0-5.5). We further investigated the impact of emerging HA substitutions seen in the ongoing cattle outbreaks, but saw little phenotypic difference, with continued exclusive binding to avian-like receptor analogues and pHs of fusion above 5.8. This suggests that the HA genes from the cattle and goat outbreaks do not pose an enhanced threat compared to circulating avian viruses. However, given the rapid evolution of H5 viruses, continuous monitoring and updated risk assessments remain essential to understanding virus zoonotic and pandemic risks.

This study investigates the epidemic trend of pyrazinamide (PZA)-resistant tuberculosis in Southern China over 11 years (2012-2022) and evaluates the mutation characteristics of PZA resistance-related genes (pncA, rpsA, and panD) in clinical Mycobacterium tuberculosis (M. tuberculosis) isolates. To fulfil these goals, we analyzed the phenotypic PZA resistance characteristics of 14,927 clinical isolates for which Bactec MGIT 960 PZA drug susceptibility testing (DST) results were available, revealing that 2,054 (13.76%) isolates were resistant to PZA. After evaluating the annual variation in the PZA resistance rate among tuberculosis cases in this region, it was observed that it decreased from 37.21% to 6.45% throughout the initial 7 years (2012-2018) and then increased from 8.01% to 12.12% over the subsequent 4 years (2019-2022). Sequences of pncA were obtained from 402 clinical M. tuberculosis complex isolates. For rpsA and panD, sequences were obtained from 360 clinical M. tuberculosis complex isolates. Mutations in pncA were found in 8 out of 223 PZA-sensitive isolates (3.59%) and 105 of 179 (58.66%) PZA-resistant isolates. Conversely, non-synonymous mutations in rpsA were identified in 5 of 137 (3.65%) PZA-resistant isolates, whereas the mutation ratio of rpsA among PZA-sensitive isolates was high at 14.03% (31/221). This difference in the rpsA mutation rate was statistically significant (P = 0.001, chi-square test). No panD mutations were observed in the 137 PZA-resistant isolates, whereas two PZA-sensitive isolates harboured point mutations in panD, including one nonsense mutation (C433 T) and another C-69 T mutation. These findings indicate that rpsA and panD may not significantly contribute to the development of PZA resistance in clinical M. tuberculosis isolates.

ABSTRACTTrichophyton species, the leading cause of dermatophytosis globally, are increasingly resistant to antifungal treatments, concerns about effective management strategies. In light of the absence of established resistance criteria for terbinafine and azoles, coupled with a dearth of research on resistance mechanisms in Trichophyton, antifungal susceptibility and drug resistance gene diversity were analyzed across 64 T. mentagrophytes, 65 T. interdigitale, and 2 T. indotineae isolates collected in China between 1999 and 2024 and 101 published T. indotineae strains. Analyses of the minimum inhibitory concentrations (MICs) of terbinafine, itraconazole, voriconazole, posaconazole, and isavuconazole revealed a concerning increase in T. indotineae with terbinafine resistance, including two novel isolates from China. Compared with T. interdigitale, T. mentagrophytes presented higher terbinafine MICs but similar azole susceptibility. Notably, 27 T. interdigitale isolates were classified as non-wild-type for terbinafine. Genetic diversity was analyzed for the SQLE, CYP51A and CYP51B gene. Specifically, T. indotineae isolates presented SQLE protein changes linked to terbinafine resistance. SQLE diversity was linked to terbinafine sensitivity, whereas alterations in CYP51A were associated with itraconazole sensitivity, with notable statistical significance evident across various protein isoforms. The relationship between protein diversity and drug sensitivity is presented in detail. Together, these findings highlight a growing prevalence of antibiotic resistance among Trichophyton and identify potential target genes for new therapies, underscoring the need for ongoing monitoring and offering directions for novel therapeutics.

The host range of HPAIV H5N1 was recently expanded to include ruminants, particularly dairy cattle in the United States (US). Shortly after, human H5N1 infection was reported in a dairy worker in Texas following exposure to infected cattle. Herein, we rescued the cattle-origin influenza A/bovine/Texas/24-029328-02/2024(H5N1, rHPbTX) and A/Texas/37/2024(H5N1, rHPhTX) viruses, identified in dairy cattle and human, respectively, and their low pathogenic forms, rLPbTX and rLPhTX, with monobasic HA cleavage sites. Intriguingly, rHPhTX replicated more efficiently than rHPbTX in mammalian and avian cells. Still, variations in the PA and NA proteins didn't affect their antiviral susceptibility to PA and NA inhibitors. Unlike rHPbTX and rLPbTX, both rHPhTX and rLPhTX exhibited higher pathogenicity and efficient replication in infected C57BL/6J mice. The lungs of rHPhTX-infected mice produced higher inflammatory cytokines/chemokines than rHPbTX-infected mice. Our results highlight the potential risk of HPAIV H5N1 virus adaptation in human and/or dairy cattle during the current multistate/multispecies outbreak in the US.