Transgenic expression of artificial microRNA targeting soybean mosaic virus P1 gene confers virus resistance in plant.

RNA silencing is an innate immune mechanism of plants against invasion by viral pathogens. Artificial microRNA (amiRNA) can be engineered to specifically induce RNA silencing against viruses in transgenic plants and has great potential for disease control. Here, we describe the development and application of amiRNA-based technology to induce resistance to soybean mosaic virus (SMV), a plant virus with a positive-sense single-stranded RNA genome. We have shown that the amiRNA targeting the SMV P1 coding region has the highest antiviral activity than those targeting other SMV genes in a transient amiRNA expression assay. We transformed the gene encoding the P1-targeting amiRNA and obtained stable transgenic Nicotiana benthamiana lines (amiR-P1-3-1-2-1 and amiR-P1-4-1-2-1). Our results have demonstrated the efficient suppression of SMV infection in the P1-targeting amiRNA transgenic plants in an expression level-dependent manner. In particular, the amiR-P1-3-1-2-1 transgenic plant showed high expression of amiR-P1 and low SMV accumulation after being challenged with SMV. Thus, a transgenic approach utilizing the amiRNA technology appears to be effective in generating resistance to SMV.

Analysis of pelvic floor muscle electromyography parameters in women with or without sexual dysfunction.

Background To investigate the differences in pelvic floor muscle (PFM) electromyography (EMG) parameters between women with or without sexual dysfunction (FSD) and their correlations. Methods Women who voluntarily participated in a questionnaire-based survey on sexual function and underwent PFM EMG in Weifang People's Hospital during the period from March 2021 to December 2021 were retrospectively enrolled. The female sexual (dys)function was measured using the Female Sexual Function Index. Glazer PFM EMG was performed using a Melander instrument (MLD A2 Deluxe). The differences in PFM EMG parameters between women with or without FSD were compared, and the relationships between PFM EMG parameters and FSD were analysed using multiple linear regression models. Results A total of 305 women were enrolled, with 163 in the FSD group and 142 in the non-FSD group. Comparisons of PFM EMG parameters between these two groups revealed that the FSD group had significantly higher peak EMG amplitude during the phasic (flick) contractions and shorter recovery latency during the tonic contractions than the non-FSD group (both P P Conclusions The results of the pelvic floor EMG in this study suggest that the pelvic floor muscles of women with FSD may be more susceptible to fatigue, and may have poorer coordination of their pelvic floor muscles.

A novel humanized tri-receptor transgenic mouse model of HAdV infection and pathogenesis.

Human adenovirus (HAdV) is a highly virulent respiratory pathogen that poses clinical challenges in terms of diagnostics and treatment. Currently, no effective therapeutic drugs or prophylactic vaccines are available for HAdV infections. One factor contributing to this deficiency is that existing animal models, including wild-type and single-receptor transgenic mice, are unsuitable for HAdV proliferation and pathology testing. In this study, a tri-receptor transgenic mouse model expressing the three best-characterized human cellular receptors for HAdV (hCAR, hCD46, and hDSG2) was generated and validated via analysis of transgene insertion, receptor mRNA expression, and protein abundance distribution. Following HAdV-7 infection, the tri-receptor mice exhibited high transcription levels at the early and late stages of the HAdV gene, as well as viral protein expression. Furthermore, the tri-receptor mice infected with HAdV exhibited dysregulated cytokine responses and multiple tissue lesions. This transgenic mouse model represents human HAdV infection and pathogenesis with more accuracy than any other reported animal model. As such, this model facilitates the comprehensive investigation of HAdV pathogenesis as well as the evaluation of potential vaccines and therapeutic modalities for HAdV.

An outbreak of acute respiratory disease caused by HAdV-55 in Beijing, China, 2020.

Human adenoviruses (HAdVs) can cause acute respiratory diseases (ARDs) worldwide, and HAdV-55 is a reemergent pathogen in recent years. In the study, we investigated an outbreak of ARD at a school due to HAdV-55 in Beijing, China, during the early outbreak of coronavirus disease 2019 (COVID-19). The epidemic prevention team was dispatched to the school to collect epidemiologic data and nasopharyngeal samples. Then, real-time reverse transcription polymerase chain reaction (PCR) and multiplex PCR assays were used to detect severe acute respiratory syndrome coronavirus 2 and other respiratory pathogens, respectively. One representative HAdV-55 isolate was selected and submitted for whole-genome sequencing using a MiSeq system and the whole-genome phylogenetic tree was conducted based on the maximum likelihood method. The outbreak lasted from January 27 to February 6, 2020, and 108 students developed fever, among whom 60 (55.56%) cases were diagnosed with HAdV-55 infection in the laboratory using real-time PCR and 56 cases were hospitalized. All the confirmed cases had a fever and 11 cases (18.33%) presented with a fever above 39°C. Other main clinical symptoms included sore throat (43.33%) and headache (43.33%). We obtained and assembled the full genome of one isolate, BJ-446, with 34 761 nucleotides in length. HAdV-55 isolate BJ-446 was 99.85% identical to strain QS-DLL, which was the first HAdV-55 strain in China isolated from an ARD outbreak in Shanxi in 2006. One and four amino acid mutations were observed in the hexon gene and the coding region of L2 pV 40.1 kDa protein, respectively. We identified the first HAdV-55 infection associated with the ARD outbreak in Beijing since the emergence of COVID-19. The study suggests that improved surveillance of HAdV is needed, although COVID-19 is still prevalent in the world.

Rapid surface reconstruction strategies for oxygen evolution reactions: chemical grafting of MXene quantum dots on Ni-Co layered double hydroxides.

The surface reconstruction of transition metal-based catalysts with their specific catalytic mechanism is currently one of the hotspots and difficulties in the electrocatalytic oxygen evolution reaction (OER). Herein, a chemical grafting strategy was proposed to facilitate the surface reconstruction of Ni-Co layered double hydroxide@MXene quantum dot (Ni-Co LDH@MQDs) electrocatalysts to optimize the OER kinetics. The surface reconstruction of Ni-Co LDH@MQDs was predicted and monitored by a combination of ab initio molecular dynamics, density functional theory and experimental verification. Compared with weak electrostatic bonds, the rapid surface evolution of electrocatalysts can be revealed due to the strong chemical grafting between the MQDs and LDHs. The reconstituted Ni-Co LDH@MQD electrocatalysts undergo an unconventional bifunctional mechanism to lower the barriers of the rate-limiting step of the OER. This work provides a research strategy for transition metal catalysts for efficient catalysis by designing surface reconfiguration.

Source-tracking of the Chinese Chikungunya viruses suggests that Indian subcontinent and Southeast Asia act as major hubs for the recent global spread of Chikungunya virus.

BACKGROUND: Chikungunya fever, caused by the Chikungunya virus (CHIKV), has become a major global health concern, causing unexpected large outbreaks in Africa, Asia, Europe, and the Americas. CHIKV is not indigenous to China, and its origin in the country is poorly understood. In particular, there is limited understanding of the recent global spread of CHIKV in the context of the CHIKV epidemic. METHODS: Here we investigated a novel Chikungunya patient who came from Myanmar to China in August, 2019. Direct genome sequencing was performed via combined MinION sequencing and BGISEQ-500 sequencing. A complete CHIKV genome dataset, including 727 CHIKV genomes retrieved from GenBank and the genome sequenced in this study, was constructed. An updated and comprehensive phylogenetic analysis was conducted to understand the virus's origin, evolution, transmission routes and genetic adaptation. RESULTS: All globally distributed CHIKV genomes were divided into West Africa, East/Central/South African and Asian genotypes. The genome sequenced in this study was located in the Indian Ocean lineage, and was closely related to a strain isolated from an Australian patient who returned from Bangladesh in 2017. A comprehensive phylogenetic analysis showed that the Chinese strains mainly originated from the Indian subcontinent and Southeast Asia. Further analyses indicated that the Indian subcontinent and Southeast Asia may act as major hubs for the recent global spread of CHIKV, leading to multiple outbreaks and epidemics. Moreover, we identified 179 distinct sites, including some undescribed sites in the structural and non-structural proteins, which exhibited apparent genetic variations associated with different CHIKV lineages. CONCLUSIONS: Here we report a novel CHIKV isolate from a chikungunya patient who came from Myanmar to China in 2019, and summarize the source and evolution of Chinese CHIKV strains. Our present findings provide a better understanding of the recent global evolution of CHIKV, highlighting the urgent need for strengthened surveillance against viral diversity.

The phenotypic and molecular characteristics of antimicrobial resistance of Salmonella enterica subsp. enterica serovar Typhimurium in Henan Province, China.

BACKGROUND: Salmonella enterica subsp. enterica serovar Typhimurium infections continue to be a significant public health threat worldwide. The aim of this study was to investigate antibiotic resistance among 147 S. Typhimurium isolates collected from patients in Henan, China from 2006 to 2015. METHODS: 147 S. Typhimurium isolates were collected from March 2006 to November 2015 in Henan Province, China. Antimicrobial susceptibility testing was performed, and the resistant genes of ciprofloxacin, cephalosporins (ceftriaxone and cefoxitin) and azithromycin were detected and sequenced. Clonal relationships were assessed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). RESULTS: Of the 147 isolates, 91.1% were multidrug resistant (MDR), with 4.1% being resistant to all antibiotic classes tested. Of concern, 13 MDR isolates were co-resistant to the first-line treatments cephalosporins and ciprofloxacin, while three were also resistant to azithromycin. Seven PFGE patterns were identified among the 13 isolates. All of the isolates could be assigned to one of four main groups, with a similarity value of 89%. MLST assigned the 147 isolates into five STs, including two dominant STs (ST19 and ST34). Of the 43 ciprofloxacin-resistant isolates, 39 carried double gyrA mutations (Ser83Phe, Asp87Asn/Tyr/Gly) and a single parC (Ser80Arg) mutation, including 1 isolate with four mutations (gyrA: Ser83Phe, Asp87Gly; parC: Ser80Arg; parE: Ser458Pro). In addition, 12 isolates not only carried mutations in gyrA and parC but also had at least one plasmid-mediated quinolone resistance (PMQR) gene. Among the 32 cephalosporin-resistant isolates, the most common extended-spectrum ß-lactamase (ESBL) gene was blaOXA-1, followed by blaCTX-M, blaTEM-1, and blaCMY-2. Moreover, the mphA gene was identified in 5 of the 15 azithromycin-resistant isolates. Four MDR isolates contained ESBL and PMQR genes, and one of them also carried mphA in addition. CONCLUSION: The high level of antibiotic resistance observed in S. Typhimurium poses a great danger to public health, so continuous surveillance of changes in antibiotic resistance is necessary.

Beta-catenin inhibits bovine parainfluenza virus type 3 replication via innate immunity pathway.

BACKGROUND: Bovine parainfluenza virus type 3 (BPIV3) is one of the important viral respiratory agents associated with the bovine respiratory disease complex (BRDC) in cattle. Previous study has demonstrated that infection of BPIV3 causes innate immune response within the host cell. ß-catenin is a key component of the Wnt/ß-catenin signal pathway which is involved in the regulation of interferon-beta (IFN-ß) transcription. Some viruses can activate while others can inhibit the Wnt/ß-catenin signaling pathway. However, the role of ß-catenin in BPIV3 infection remains unclear. RESULTS: Here we found that the expression of ß-catenin mRNA was up-regulated and ß-catenin protein was down-regulated after BPIV3 infection in MDBK cells. Moreover, it was confirmed that overexpression of ß-catenin suppressed BPIV3 replication and knockdown of ß-catenin promoted viral replication, suggesting that ß-catenin inhibits BPIV3 replication. Furthermore, IFN-ß signal pathway and virus titer analysis using the GSK3ß inhibitor (LiCl) revealed that Wnt/ß-catenin can serve as a mechanism to suppress virus replication in infected cells. The results indicated that LiCl promoted the expression and accumulation in the nucleus of ß-catenin, which further promoted the expression of IFN-ß and OSA1 and suppressed BPIV3 replication. Most importantly, BPIV3 down-regulating ß-catenin protein expression was due to degradation of GSK3ß mediated proteasome pathway. CONCLUSIONS: In summary, we discovered the relationship between ß-catenin and BPIV3 replication. These results provided further insight into the study of BPIV3 pathogenesis.

Antibiotic resistance and molecular characterization of the hydrogen sulfide-negative phenotype among diverse Salmonella serovars in China.

BACKGROUND: Among 2179 Salmonella isolates obtained during national surveillance for salmonellosis in China from 2005 to 2013, we identified 46 non-H2S-producing strains originating from different sources. METHODS: The isolates were characterized in terms of antibiotic resistance and genetic variability by pulsed-field gel electrophoresis and multilocus sequence typing. Mutation in the phs operon, which may account for the non-H2S-producing phenotype of the isolated Salmonella strains, was performed in this study. RESULTS: Among isolated non-H2S-producing Salmonella strains, more than 50% were recovered from diarrhea patients, of which H2S-negative S. Gallinarum, S. Typhimurium, S. Choleraesuis and S. Paratyphi A isolates constituted 76%. H2S-negative isolates exhibited a high rate of resistance to ticarcillin, ampicillin, and tetracycline, and eight of them had the multidrug resistance phenotype. Most H2S-negative Salmonella isolates had similar pulsed-field gel electrophoresis profiles and the same sequence type as H2S-positive strains, indicating a close origin, but carried mutations in the phsA gene, which may account for the non-H2S-producing phenotype. CONCLUSIONS: Our data indicate that multiple H2S-negative strains have emerged and persist in China, emphasizing the necessity to implement efficient surveillance measures for controlling dissemination of these atypical Salmonella strains.

A Waterborne Outbreak of Shigella sonnei with Resistance to Azithromycin and Third-Generation Cephalosporins in China in 2015.

Here, we report for the first time a waterborne outbreak of Shigella sonnei in China in 2015. Eleven multidrug-resistant (MDR) S. sonnei isolates were recovered, showing high resistance to azithromycin and third-generation cephalosporins in particular, due to an mph(A)- and blaCTX-M-14-harboring IncB/O/K/Z group transmissible plasmid of 104,285 kb in size. Our study highlights the potential prevalence of the MDR outbreak of S. sonnei in China and its further dissemination worldwide with the development of globalization.

Inhibition of TLR4 signaling by Brucella TIR-containing protein TcpB-derived decoy peptides.

Brucella spp. avoid host immune recognition and thus, weaken the immune response to infection. The Toll/interleukin-1 receptor (TIR) domain-containing protein (TcpB/Btp1) of Brucella spp. is thought to be involved in blocking host innate immune responses by binding to adaptors downstream of Toll-like receptors. In this study, based on the observation that TcpB binds to the host target proteins, MAL, through the TIR domain, we examined decoy peptides from TcpB TIR domains and found that TB-8 and TB-9 substantially inhibit lipopolysaccharide (LPS)-induced signaling in vitro and in vivo. Both these peptides share a common loop, the DD loop, indicating a novel structural region mediating TIR interactions. The inhibition of LPS signaling by TB-8 and TB-9 shows no preference to MyD88-dependent cytokines, such as TNF-α and IL-1ß or TRIF-dependent cytokines including IFN-ß and IL-6. Furthermore, these two peptides rescue the virulence of Brucella ΔtcpB mutants at the cellular level, indicating key roles of the DD loop in Brucella pathogenesis. In conclusion, identification of inhibitors from the bacterial TIR domains is helpful not only for illustrating interacting mechanisms between TIR domains and bacterial pathogenesis, but also for developing novel signaling inhibitors and therapeutics for human inflammatory diseases.

Development of a rapid recombinase polymerase amplification assay for detection of Brucella in blood samples.

A rapid and sensitive recombinase polymerase amplification (RPA) assay, Bruce-RPA, was developed for detection of Brucella. The assay could detect as few as 3 copies of Brucella per reaction within 20 min. Bruce-RPA represents a candidate point-of-care diagnosis assay for human brucellosis.

Genomic and Phenotypic Analysis of bla KPC-2 Associated Carbapenem Resistance in Klebsiella aerogenes: Insights into Clonal Spread and Resistance Mechanisms Across Hospital Departments in Beijing.

Purpose: This study conducted an phenotypic and whole-genome sequencing analysis with Klebsiella aerogenes to elucidate its clinical epidemiological characteristics, antimicrobial resistance (AMR) phenotype, biofilm formation ability and hemolytic activity testing, AMR genes and phylogenetic relationships, so as to provide a further understanding of the intra-hospital strain transmission. Methods: Samples were collected from a hospital in Beijing between 2020 and 2022. All strains underwent bacterial identification, antimicrobial susceptibility testing (AST) using the VITEK-2 compact system. Biofilm formation ability and hemolytic activity were tested. Second-generation sequencing was applied to all strains, with those carrying the bla KPC gene were selected for third-generation sequencing. Whole-genome analysis identified resistance genes, plasmid types, MLST typing, and phylogenetic relationships. Plasmids were assembled to detect plasmid structures and AMR gene location. Results: Among the 42 K. aerogenes isolates, 21 were carbapenem-resistant K. aerogenes (CRKA). All strains exhibited strong biofilm formation and no hemolytic activity. Most were sourced from sputum (83.3%). CRKA demonstrated extensive resistance to antibiotics, particularly ß-lactamase inhibitors and Cefotetan. This resistance pattern was closely associated with the presence of an IncFII(pHN7A8) plasmid, which carried multiple resistance genes, including bla KPC-2, bla CTX-M-65, bla TEM-1, rmtB and a large number of mobile elements. The majority of CRKA strains clustered within the same branch of the phylogenetic tree, exhibiting minimal single nucleotide polymorphism (0-13 SNPs) differences, and they shared the same sequence type (ST292), resistance genes, and plasmids, originating from different departments, suggesting clonal transmission among the hospital. Conclusion: Our research reveals that the clonal transmission of CRKA occurs across various departments within the hospital. The widespread resistance observed in CRKA, attributed to the presence of bla KPC and ESBLs genes, underscores the need for heightened vigilance to prevent the further dissemination of CRKA within the hospital and, potentially, throughout the wider community.

Indirubin-3'-monoxime exhibits potent antiviral and anti-inflammatory effects against human adenoviruses in vitro and in vivo.

Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3'-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.

Genomic insights and antimicrobial resistance profiles of CRKP and non-CRKP isolates in a Beijing geriatric medical center: emphasizing the blaKPC-2 carrying high-risk clones and their spread.

Background: The escalating resistance of Klebsiella pneumoniae, a prevalent pathogen in healthcare settings, especially its carbapenem-resistant K. pneumoniae (CRKP), to a wide array of antibiotics, notably ß-lactams, constitutes a formidable challenge for healthcare and global public health management. Methods: This research compared the resistance phenotypes and genomic profiles of CRKP and Non-CRKP isolates in a Beijing hospital, focusing on high-risk blaKPC-2 gene-bearing CRKP clones and the structure of mobile genetic elements facilitating their spread across hospital departments. Forty K. pneumoniae isolates were collected from various departments of the hospital and subjected to antimicrobial susceptibility testing and whole-genome sequencing to analyze their resistance phenotypes and genomic features. Results: The study revealed that among the 31 CRKP isolates, ST11 is the most common sequence type, with K47 and OL101 being the dominant capsule types, primarily observed in the respiratory department. In terms of antimicrobial susceptibility: 87.5% of the isolates exhibited multidrug resistance (MDR), with a high resistance rate of 30% against tigecycline. All CRKP isolates demonstrated resistance to multiple drug classes (≥5 CLSI classes). Non-CRKP isolates also showed high resistance rates to minocycline and doxycycline (77.8%). the ST11-KL47-OL101 type emerged as the predominant clone among the CRKP isolates carrying the blaKPC-2 gene. This dominance appears to be mediated by the pKpnR03_2 plasmid, which harbors not only blaKPC-2 and rmtb but also gene clusters pertinent to iron transport and arsenic resistance. These isolates, clustering in the C3 clade of the phylogenetic tree, exhibited minor genetic variations and close evolutionary relationships, suggesting a plasmid-driven spread across various hospital departments. Conclusion: In summary, our study highlights the extensive spread of antibiotic-resistant K. pneumoniae across various departments in our hospital, with a particular emphasis on the dominant clonal proliferation of the ST11-KL47-OL101 CRKP strain. This finding underscores the significant role of plasmid-mediated gene transfer in the evolution and dissemination of resistant strains within hospital environments. The study emphasizes the necessity for ongoing surveillance of antibiotic resistance and genomic analysis in hospital settings to effectively monitor and manage these challenges.

Characterization of a Salmonella enterica serovar Typhimurium lineage with rough colony morphology and multidrug resistance.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (-44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.

Targeting the chromatin structural changes of antitumor immunity.

Epigenomic imbalance drives abnormal transcriptional processes, promoting the onset and progression of cancer. Although defective gene regulation generally affects carcinogenesis and tumor suppression networks, tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes, which may have significant implications for the development and application of epigenetic therapy, cancer immunotherapy, and their combinations. Herein, we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes, DNA methylation, histone post-translational modification, and chromatin structure in tumor immunogenicity, and introduce these epigenetic research methods. We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immunotherapy through the complex interaction between cancer epigenetics and cancer immunology.

Successful clearance of persistent SARS-CoV-2 asymptomatic infection following a single dose of Ad5-nCoV vaccine.

Persistent asymptomatic (PA) SARS-CoV-2 infections have been identified. The immune responses in these patients are unclear, and the development of effective treatments for these patients is needed. Here, we report a cohort of 23 PA cases carrying viral RNA for up to 191 days. PA cases displayed low levels of inflammatory and interferon response, weak antibody response, diminished circulating follicular helper T cells (cTfh), and inadequate specific CD4+ and CD8+ T-cell responses during infection, which is distinct from symptomatic infections and resembling impaired immune activation. Administration of a single dose of Ad5-nCoV vaccine to 10 of these PA cases elicited rapid and robust antibody responses as well as coordinated B-cell and cTfh responses, resulting in successful viral clearance. Vaccine-induced antibodies were able to neutralize various variants of concern and persisted for over 6 months, indicating long-term protection. Therefore, our study provides an insight into the immune status of PA infections and highlights vaccination as a potential treatment for prolonged SARS-CoV-2 infections.

Genome sequence of an OXA23-producing, carbapenem-resistant Acinetobacter baumannii strain of sequence type ST75.

The increase of Acinetobacter baumannii resistance to carbapenems is of great concern. OXA23 is one of the most prevalent carbapenemases of A. baumannii that causes outbreaks. Here, we announce the genome sequence of an OXA23-producing A. baumannii strain assigned ST75, a newly emerged sequence type harboring carbapenemase.

Altered Transcriptome of the B. melitensis Vaccine Candidate 16MΔvjbR, Implications for Development of Genetically Marked Live Vaccine.

The VjbR protein induced antibody responses in both human and animal brucellosis, and the vjbR mutant 16MΔvjbR is an ideal vaccine candidate because of the feasibility of using the VjbR as diagnostic antigen. To further characterize this vaccine candidate and provide information for vaccine development, in the present study, a whole genome DNA microarray of 16M were used to compare the transcriptome of the vjbR mutant to that of the wild type strains. A total of 126 genes were greatly differentially expressed in the vjbR mutant. A great proportion of virB and flagellar genes were differentially expressed in the vjbR mutant, implying that the vjbR regulate expression of virulence genes by sensing intracellular environments. Interestingly, the virB genes are regulated by the vjbR in independent manners as shown by their different fold changes and transcription abundances. A number of genes involved in translation, stress response, amino acid transport and metabolism, cell wall/membrane biogenesis, energy production and conversion, translation were differentially expressed. The vjbR mutant showed increased sensitivity to stresses of nutrition limitation, oxidative stress and acidification, and decreased survival in macrophage and mice, being consistent with its transcription profiles. These results indicated that the quorum sensing regulator vjbR could sense intracellular environments and response to them by regulate expression of virulence genes and other intracellular survival related genes, and therefore contribute to Brucella survival in host cells. This also provided direct evidence for the rational vaccine design by using antigenic global regulator for future development of genetically marked vaccine for brucellosis.