Positive Rate of Different Hepatitis B Virus Serological Markers in Peking Union Medical College Hospital,a General Tertiary Hospital in Beijing

Objectives To investigate the positive rate of different hepatitis B virus （HBV） serological markers, and the demographic factors related to HBV infection. Methods We enrolled all patients tested for HBV serological markers, such as HBV surface antigen （HBsAg）, HBV surface antibody （HBsAb）, hepatitis B e antigen （HBeAg）, hepatitis B e antibody （HBeAb）, HBV core antibody （HBcAb）, and HBV-DNA from July 2008 to July 2009 in Peking Union Medical College Hospital. The positive rate of each HBV serological marker was calculated according to gender, age, and department, respectively. The positive rates of HBV-DNA among patients with positive HBsAg were also analyzed. Results Among 27 409 samples included, 2681 （9.8%） were HBsAg positive. When patients were divided into 9 age groups, the age-specific positive rate of HBsAg was 1.2%, 9.6%, 12.3%, 10.9%, 10.3%, 9.7%, 8.0%, 5.8%, and 4.3%, respectively. The positive rate of HBsAg in non-surgical department, surgical department, and health examination center was 16.2%, 5.8%, and 4.7%, respectively. The positive rate of HBsAg of males （13.3%） was higher than that of females （7.3%, P=0.000）. Among the 2681 HBsAg （＋） patients, 1230 （45.9%） had HBV-DNA test, of whom 564 （45.9%） were positive. Patients with HBsAg （＋）, HBeAg （＋）, and HBcAg （＋） result usually had high positive rate of HBV-DNA results （71.8%, P=0.000）. Conclusions Among this group of patients in our hospital, the positive rate of HBsAg was relatively high. Age group of 20-29, males, and patients in non-surgical departments were factors associated with high positive rate of HBsAg.

Diagnosis and Clinical Management of Acute Severe Hepatitis of Unknown Origin: Operational Recommendation of Peking Union Medical College Hospital

Around 450 cases of acute severe hepatitis of unknown origin in children have been reported in 21 countries and region globally since April 2022,which has exceeded the past annual incidences of related regions,and has aroused wide concern.Affected patients were predominantly children under 16years of age,presented with symptoms of acute hepatitis with markedly elevated liver enzymes,and had been ruled out of common viral infections such as hepatitis A,B,C,D,and E.Similar cases have not been reported in China yet.However,considering that the severe acute hepatitis has involved worldwide areas,still with unknown origin,and incidences of severity is relatively high,we formulated this recommendation to standardize diagnosis and treatment of acute severe hepatitis of unknown origin in Peking Union Medical College Hospital,to get fully prepared to the possible public health events.

DETECTION OF PLATELET-DERIVED MICROPARTICLES USING FLOW CYTOMETRY AND ITS CLINICAL APPLICATION

Objective.To establish a flow cytometric internal standard method for counting platelet-derived microparti-cles(PMPs)and to study its clinical significance. Methods. PMPs suspension(platelet poor plasma,PPP) was extracted by gradual centrifugation. According to the size of PMPs,3 μm and 0.8μm latex beads were used as internal standards for the quantitation. PMPs were counted by adjusting flow cytometric discrimination and voltage of forward scatter and side scatter. Results. In 30 healthy donors,the average concentration of resting PMPs was(1.2×105±5.7×104 )/ml and that of activated PMPs was(1.6×106±9.1×105)/ml. Compared with healthy donors,PMPs mean value was significantly higher(P< 0.001)in 18 patients with coronary artery disease,12 with acute cerebral infraction and 23 with chronic renal failure[the average PMPs concentration,( 6.1×105±2.5×105 )/ml, ( 6.8×105±3.4×105)/ml and(5.9×105±3.1×105)/ml respectively]. However,no significant difference in PMPs concentration was observed in 25 patients with acute leukemia and severe thrombocytopenia during the aplastic phase after chemotherapy [1.3×105±6.1×104)/ml,(P >0.05)] .Conclusions. PMPs is a useful indicator in monitoring platelet activation,and plays an important role in thrombotic disease. By flow cytometric internal standard method,PMPs can be counted rapidly and accurately,which may be very helpful in interlaboratory comparative studies.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline(updated version)

The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnosis and treatment guidelines for clinicians caring for patients are needed.In the early stage,we have issued"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline.We formed a working group of clinical experts and methodologists.The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge management.We searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Recommendations were either strong or weak,or in the form of ungraded consensus-based statement.Finally,we issued 34 statements.Among them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based statement.They covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung transplantation,invasive or noninvasive ventilation,and extracorporeal membrane oxygenation(ECMO)),and discharge management(including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge).We also created two figures of these recommendations for the implementation purpose.We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Innovative integration of lung ultrasound and wearable monitoring for predicting pulmonary complications in colorectal surgery:A prospective study

BACKGROUND Postoperative pulmonary complications(PPCs)are common in patients who undergo colorectal surgery.Studies have focused on how to accurately diagnose and reduce the incidence of PPCs.Lung ultrasound has been proven to be useful in preoperative monitoring and postoperative care after cardiopulmonary surgery.However,lung ultrasound has not been studied in abdominal surgeries and has not been used with wearable devices to evaluate the influence of postoperative ambulation on the incidence of PPCs.AIM To investigate the relationship between lung ultrasound scores,PPCs,and postoperative physical activity levels in patients who underwent colorectal surgery.METHODS In this prospective observational study conducted from November 1,2019 to August 1,2020,patients who underwent colorectal surgery underwent daily bedside ultrasonography from the day before surgery to postoperative day(POD)5.Lung ultrasound scores and PPCs were recorded and analyzed to investigate their relationship.Pedometer bracelets measured the daily movement distance for 5 days post-surgery,and the correlation between postoperative activity levels and lung ultrasound scores was examined.RESULTS Thirteen cases of PPCs was observed in the cohort of 101 patients.The mean(standard deviation)peak lung ultrasound score was 5.32(2.52).Patients with a lung ultrasound score of≥6 constituted the high-risk group.High-risk lung ultrasound scores were associated with an increased incidence of PPCs after colorectal surgery(logistic regression coefficient,1.715;odds ratio,5.556).Postoperative movement distance was negatively associated with the lung ultrasound scores[Spearman’s rank correlation coefficient(r),-0.356,P<0.05].CONCLUSION Lung ultrasound effectively evaluates pulmonary condition post-colorectal surgery.Early ambulation and respiratory exercises in the initial two PODs will reduce PPCs and optimize postoperative care in patients undergoing colorectal surgery.

Landscape of PD-1/PD-L1 Regulation and Targeted Immunotherapy

Programmed cell death protein 1(PD-1)/programmed death ligand 1(PD-L1)is a significant immune checkpoint,and the dysfunction of this axis contributes to tumor metastasis and immune escape.PI3K/Akt/mTOR and MAPK signal network induces PD-1/PD-L1 expression and facilitates tumor progression.Transcriptional factors such as hypoxia induced factors,PTEN,p53,CDK5,BRD4,STAT modulate PD-1/PDL1 expression.PD-1/PD-L1 level is also regulated via epigenetic and post-translational manner.The underlying mechanisms mentioned above may provide potential targets for tumor treatment.At present,the combination therapy of PD-1/PD-L1 monoclonal antibodies plus small molecular inhibitors has achieved good outcomes in tumor treatment.

Molecular Epidemiology of Oxacillin-resistant Staphylococcus aureus and in vitro Activity of Glycopeptides against Staphylococcus species

The purpose of this subject was to investigate molecular epidemiology of oxacillin-resistant Staphylococcus aureus (MRSA) isolated from hospitalized patients, and to survey the in vitro activity of teicoplanin, vancomycin and other 9 antibiotics against Staphylococcus species . MRSA were detected by oxacillin-NaCl-containing screen agar. The homology of nosocomial MRSA from ICU and RCU was determined by pulse-field gel electrophoresis. Agar diffusion, E test and agar dilution were used to compare the in vitro activity of teicoplanin and vancomycin against Staphylococcus spp from 2001 to 2003 at Peking Union Medical College Hospital. WHONET-5.3 software was used to analyze the antimicrobial susceptibility data. From 2001 to 2003, the prevalences of MRSA were 56.5%, 65.3%, 64.7%, respectively. PFGE found most of MRSA from ICU and RCU were closely related. All of S.aureus and S.epidimidis isolates were susceptible to teicoplanin and vancomycin from 2001 to 2003. However, 1 isolate of S.haemolyticus was resistant and 9 isolates intermediate to teicoplanin. The minimal inhibitory concentration of teicoplanin did not correlate well with zone diameter, when inoculum increased by 100 folds, the zone diameters of teicoplanin decreased more greatly than those of vancomycin. In 2002, severe outbreaks caused by MRSA strains had been found in ICU and RCU wards. Teicoplanin and vancomycin had good activity against clinical isolates of Staphylococci spp . Teicoplanin was less active than vancomycin against S.haemolyticus . Most of S.haemolyticus isolates were intermediate to teicoplanin. Antimicrobial susceptibility testing of teicoplanin was influenced by the diffusion speed in the agar and inoculum size.

Diagnosis of Tumor-Like Polypoid Lesions of Gallbladder by Serum Proteomic Fingerprint

Objective： To search the specific serum proteins in tumor-like polypoid lesions of the gallbladder（PLG） patients. Methods： Surface enhanced laser desorption/ionization time of flight mass spectrometry （SELDI-TOF-MS） technique and WCX Magnetic Beads were used to detect the serum proteomic fingerprint of 23 patients with tumor-like PLG, 21 patients with non tumor-like PLG and 26 normal persons. Biomarker Wizard and Biomarker Patterns Software were used in combination to analyze the data. Results： In the preliminary screening, 22 representative specific proteins for tumor-like PLG were found. Seven specific proteins showed increased expression and 15 specific proteins showed decreased expression in the tumor-like PLG patients. Three specific proteins are selected for the diagnosis of the tumor-like PLG.. Conclusion： SELDI-TOF-MS technique can be used to select specific proteins for tumor-like PLG patients, which may be useful for the diagnosis of the tumor-like PLG and the differential diagnosis with the non tumor-like PLG.

An unusual case report of Burkholderia cepacia endophthalmitis

Dear Editor,I am Huan Chen from the Department of Ophthalmology,Peking Union Medical College Hospital in Beijing,China.I am writing this letter to present an unusual case of Burkholderia cepacia endophthalmitis.Burkholderia cepacia[Burkholderia cepacian complex(Bcc)]is a group of genetically unique Gram-negative bacilli with similar phenotypes,belonging to the genus pseudomonas,which is widely found in water,soil and plants.

A single nucleotide polymorphism in the IL1RL1 gene is associated with Behcet's disease in a Chinese Han population

AIM:To explore the association of single nucleotide polymorphisms(SNPs)in the IL33/IL1RL1 gene region with the susceptibility to Behcet’s disease(BD)in a Chinese Han population.METHODS:A total of eight SNPs in the candidate gene region(rs11792633,rs7025417,rs10975519 and rs1048274 in IL33;rs2310220,rs12712142,rs13424006 and rs3821204 in IL1RL1)were genotyped in783 BD patients and 701 healthy controls by the Sequenom Mass Array i PLEX platform.RESULTS:A statistically significant association was observed between IL1RL1 rs12712142 and BD patients.The frequency of IL1RL1 rs12712142 variant allele A was significantly lower in BD patients than that in controls(OR=0.8,95%CI:0.69-0.94,Pc=0.039);the genotype distribution(Pc=0.043)and additive and dominant genetic model analyses(OR=0.8,95%CI:0.69-0.94,Pc=0.040 and OR=0.72,95%CI:0.58-0.88,Pc=0.011)also indicated a strong association between rs12712142 and BD patients.CONCLUSION:This is the first study to reveal the association between IL1RL1 rs12712142 variant allele A and the decreased risk of BD in the Chinese Han population,indicating a protective role of IL1RL1 in the pathogenesis of BD.

A Serum Biomarker Model to Diagnose Pancreatic Cancer Using Proteomic Fingerprint Technology

OBJECTIVE To establish a serum protein pattern model for screening pancreatic cancer. METHODS Twenty-nine serum samples from patients with pancreatic cancer were collected before surgery, and an additional 57 serum samples from age and sex-matched individuals without cancer were used as controls. WCX magnetic beans and a PBS II-C protein chip reader （Ciphergen Biosystems Inc） were employed to detect the protein fingerprint expression of all serum samples. The resulting profiles comparing serum from cancer and normal patients were analyzed with the Biomarker Wizard system, to establish a model using the Biomarker Pattern system software. A double-blind test was used to determine the sensitivity and specificity of the model.RESULTS A group of 4 biomarkers （relative molecular weights were 5,705 Da, 4,935 Da, 5,318 Da, 3,243 Da） were selected to set up a decision tree to produce the classification model to effectively screen pancreatic cancer patients. The results yielded a sensitivity of 100% （20/20）, specificity of 97.4% （37/38）. The ROC curve was 99.7%. A double-blind test used to challenge the model resulted in a sensitivity of 88.9% and a specificity of 89.5%. CONCLUSION New serum biomarkers of pancreatic cancer have been identified. The pattern of combined markers provides a powerful and reliable diagnostic method for pancreatic cancer with high sensitivity and specificity.

The biology,function,and applications of exosomes in cancer

Exosomes are cell-derived nano vesicles with diameters from 30 to 150 nm,released upon fusion of multi vesicular bodies with the cell surface.They can transport nucleic acids,proteins,and lipids for intercellular communication and activate signaling pathways in target cells.In cancers,exosomes may participate in growth and metastasis of tumors by regulating the immune response,blocking the epithelial-mesenchymal transition,and promoting angiogenesis.They are also involved in the development of resistance to chemotherapeutic drugs.Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers.Because of their amphipathic structure,exosomes are natural drug delivery vehicles for cancer therapy.

Spectrum and antimicrobial resistance of common pathogenic bacteria isolated from patients with acute exacerbation of chronic obstructive pulmonary disease in mainland of China

Background Bacteria-induced respiratory infection has been long considered to be the major cause of acute exacerbation of chronic obstructive pulmonary disease （AECOPD）.Therefore,a clear picture about the distribution and drug-resistance of pathogenic bacteria in the lower airways should be helpful for treatment of the disease.So far,data on this topic among Chinese are lacking.Methods A surveillance study was performed in consecutive patients with AECOPD at five areas in China between October 2006 and April 2008.The sputum from these patients was cultured and isolated for bacteria.Agar dilution method was used to determine the minimal inhibitory concentrations （MICs） of levofloxacin and other 15 antibiotics against these strains.Results Three hundred and fifty-nine pathogenic bacterial strains were isolated among 884 patients with AECOPD.The predominant bacteria were Pseudomonas aeruginosa （21.7%）,Klebsiella pneumoniae （12.3%）,Haemophilus influenzae （14.2%） and Streptococcus pneumoniae （11.7%）,followed by Haemophilus parainfluenzae （9.5%）,Acinetobacter baumannii （7.8%）,Moraxella catarrhalis （6.4%） and Escherichia coli （3.6%）.The majority of bacterial pathogens isolated in this study were susceptible to fluoroquinolones,ceftazidime,cefepime and imipenem.Conclusions Gram-negative bacilli are the leading pathogens in patients with AECOPD in China.Haemophilus parainfluenzae may be one of the most important pathogens in AECOPD.This study provides evidence for local surveillance of AECOPD pathogens and appropriate choice of antimicrobials in China.

Prospective evaluation of heparin-induced thrombocytopenia expert probability and 4T scores in Chinese patients with suspected heparin-induced thrombocytopenia

Background: Diagnosis of heparin-induced thrombocytopenia (HIT) is challenging. This study aimed to compare the diagnostic performance of HIT expert probability (HEP) and 4T scores, and to evaluate the inter-observer reliability for the 4T score in a clinical setting. Methods: This prospective study included HIT-suspected patients between 2016 and 2018. Three hematologists assessed the HEP and 4T scores. Correlations between scores and anti-platelet factor 4 (anti-PF4)/heparin antibodies were evaluated. Receiver operating characteristic curves and area under the curve (AUC) were used to assess the predictive accuracy of these two scoring models. The intraclass correlation coefficient (ICC) was used to assess the inter-observer agreement of 4T scores between residents and hematologists. Results: Of the 89 subjects included, 22 (24.7%) were positive for anti-PF4/heparin antibody. The correlations between antibody titer and either HEP or 4T scores were similar (r = 0.392, P < 0.01 for the HEP score;r = 0.444, P < 0.01 for the 4T score). No significant difference in the diagnostic performance was displayed between these two scores (AUC for the HEP score: 0.778 vs. AUC for the 4T score: 0.741, P = 0.357). Only 72 4T scores were collected from the residents, with a surprisingly low percentage of observers (43.1%) presenting the four individual item scores which made up their 4T score. The AUC of 4T score assessed by residents and hematologists was 0.657 (95% confidence interval [CI]: 536–0.765) and 0.780 (95% CI: 0.667–0.869, P < 0.05), respectively. The ICC of 4T score between residents and hematologists was 0.49 (95% CI: 0.29–0.65, P < 0.01), demonstrating a fair inter-observer agreement. Conclusions: The HEP score does not display a better performance for predicting HIT than the 4T score. With the unsatisfactory completion rate, the inter-observer agreement of 4T score in a tertiary hospital is fair, underscoring the necessity for continuing education for physicians.

Reticulocyte hemoglobin content in the diagnosis of iron deficiency in Chinese pre-menopausal women

Pre-menopausal women are at risk for iron deficiency due to menstrual blood losses. The prevalence rates （PR） of iron depletion, iron deficiency anemia （IDA）, and iron deficiency were 34.4%, 15.1% and 49.5% in pre-menopausal non-pregnant women respectively in China.1 Traditionally, the diagnosis of iron deficiency relies on the hematological markers （hemoglobin （HGB）, mean corpuscular volume （MCV）, mean corpuscular hemoglobin （MCH）, red cell distribution width （RDW）） and biochemical markers （serum ferritin （SF）, serum iron （SI）, transferrin saturation （TS）, total iron-binding capacity （TIBC））. Recently, the reticulocyte hemoglobin content （CHr） is considered to be used as a marker of iron deficiency.2 The aim of this study was to compare the diagnostic efficiency of CHr with the old markers in diagnosis of iron deficiency in Chinese pre-menopausal women.

Differences in intestinal microbiome are associated with the mortality of COVID-19 patients in intensive care units

Dear Editor,Coronavirus disease 2019(COVID-19),caused by infection with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has developed into a global pandemic.In addition to the common respiratory symptoms,a significant proportion of COVID-19 patients experience gastrointestinal symptoms,such as diarrhea,nausea,and vomiting(Parasa et al.,2020).

Multilocus sequence typing indicates diverse origins of invasive Candida tropicalis isolates in China

Background According to data from the China Hospital Invasive Fungal Surveillance Net （CHIF-NET） 2010, Candida tropica/is （C. tropica/is） is the third most common pathogen causing invasive candidiasis. Moreover, the majority of fluconazole-resistant C. tropicalis isolates were from a single hospital. Therefore, a molecular epidemiological survey is necessary to investigate the genetic relatedness of C. tropica/is isolates in China. Methods In this study, 48 C. tropicalis isolates causing invasive fungal infections from four tertiary hospitals in China were studied. All the isolates were identified by sequencing the internal transcribed spacer region. Antifungal susceptibility to triazoles, amphotericin B, and caspofungin was determined by the Clinical and Laboratory Standards Institute standard broth microdilution method. Multilocus sequence typing （MLST） was performed, and phylogenetic analysis was further performed by the eBURST and maximum parsimony （MP） methods to characterize the genetic relatedness of isolates. Results MLST discriminated 40 diploid sequence types （DSTs） among 48 isolates, including 36 novel DSTs, and the XYR1 gene showed the highest discriminatory power. The DSTs obtained from this study were compared with those of previously reported C. tropicalis isolates, and there was poor type alignment with regional strains. Nine groups and 11 singletons were identified by eBURST, whereas two groups and 10 subgroups were clustered by MP analysis. Generally, there were no obvious correlations between clonal clusters generated and the specimen source or hospital origin. Seven fiuconazole-resistant isolates were confirmed and assigned to three distinguishable branches. Conclusions The results suggested diverse origins of invasive C. tropicalis isolates in China. Although most invasive C. tropicalis strains in the mainland of China were clustered with previously characterized Asian isolates, major C. tropicalis clusters identified in this study were genetically distinct from those of other geographic regions.

Single cell metabolic phenome and genome via the ramanome technology platform:Precision medicine of infectious diseases at the ultimate precision?

Due to the limitations of existing approaches,a rapid,sensitive,accurate,comprehensive,and generally applicable strategy to diagnose and treat bacterial and fungal infections remains a major challenge.Here,based on the ramanome technology platform,we propose a culture‐free,one cell resolution,phenome‐genome‐combined strategy called single‐cell identification,viability and vitality tests and source tracking(SCIVVS).For each cell directly extracted from a clinical specimen,the fingerprint region of the D2O‐probed single cell Raman spectrum(SCRS)enables species‐level identification based on a reference SCRS database of pathogen species,whereas the C‐D band accurately quantifies viability,metabolic vitality,phenotypic susceptibility to antimicrobials,and their intercellular heterogeneity.Moreover,to source track a cell,Raman‐activated cell sorting followed by sequencing or cultivation proceeds,producinging an indexed,high coverage genome assembly or a pure culture from precisely one pathogenic cell.Finally,an integrated SCIVVS workflow that features automated profiling and sorting of metabolic and morphological phenomes can complete the entire process in only a few hours.Because it resolves heterogeneity for both the metabolic phenome and genome,targets functions,can be automated,and is orders‐of‐magnitude faster while cost‐effective,SCIVVS is a new technological and data framework to diagnose and treat bacterial and fungal infections in various clinical and disease control settings.

A forkhead transcription factor contributes to the regulatory differences of pathogenicity in closely related fungal pathogens

Cryptococcus neoformans and its sister species Cryptococcus deuterogattii are important human fungal pathogens.Despite their phylogenetically close relationship,these two Cryptococcus pathogens are greatly different in their clinical characteristics.However,the determinants underlying the regulatory differences of their pathogenicity remain largely unknown.Here,we show that the forkhead transcription factor Hcm1 promotes infection in C.neoformans but not in C.deuterogattii.Monitoring in vitro and in vivo fitness outcomes of multiple clinical isolates from the two pathogens indicates that Hcm1 mediates pathogenicity in C.neoformans through its key involvement in oxidative stress defense.By comparison,Hcm1 is not critical for antioxidation in C.deuterogattii.Furthermore,we identified SRX1,which encodes the antioxidant sulfiredoxin,as a conserved target of Hcm1 in two Cryptococcus pathogens.Like HCM1,SRX1 had a greater role in antioxidation in C.neoformans than in C.deuterogattii.Significantly,overexpression of SRX1 can largely rescue the defective pathogenicity caused by the absence of Hcm1 in C.neoformans.Conversely,Srx1 is dispensable for virulence in C.deuterogattii.Overall,our findings demonstrate that the difference in the contribution of the antioxidant sulfiredoxin to oxidative stress defense underlies the Hcm1-mediated regulatory differences of pathogenicity in two closely related pathogens.

Insights on evolution of virulence and resistance from the whole-genome analysis of a predominant methicillin-resistant Staphylococcus aureus clone sequence type 239 in China

Earlier, we reported that ST239 was the15-year predominant methicillin-resistant Staphylococcus aureus(MRSA) clone in China. In this study, MRSA strain CN79 belonging to ST239 and isolated from blood was used to determine the whole genome sequence. Comparative genomics analysis was done between MRSA CN79and 25 sequenced S. aureus in the NCBI GenBank database. A total of 2,734 protein-encoding genes were identified in the MRSA CN79 genome, which carries 11antibiotic resistance genes and 65 virulence genes. Two prophages phiCN79A and phiNM3-like were found on the MRSA CN79 genome. MRSA CN79 carries 30 specific genes that are absent from the 25 sequenced S. aureus genomes. Most of them were prophage-related genes.Several antibiotic resistance genes, such as b-lactamase and ABC-type multidrug transport system gene, were located on the genomic island mSab. The antibiotic resistance genes, such as tet(M), ermA1, and blaZ, were also located on different transposons. The virulence genes sea,map, hlb, and sak are located on phiNM3-like prophage and the exotoxin genes are carried on the genomic island mSaa. These results suggest that ST239 MRSA strains are widespread owing to horizontal acquisition of the mobile genetic elements harbored antibiotic resistance genes and virulence genes in response to environmental selective pressures, such as antibiotics and the human immune system during evolution.