Pyrosequencing analysis of bacterial community changes in dental unit waterlines after chlorogenic acid treatment.

Introduction: The contamination of dental unit waterlines (DUWLs) poses a significant risk of cross-infection in dentistry. Although chemical disinfectants have been effective in reducing number of bacteria, they do have limitations. Methods: This study aimed to investigate the potential of chlorogenic acid, a natural substance with broadspectrum antibacterial properties, for treating DUWLs. Over a period of three months, we analyzed the microbial communities in 149 DUWLs samples collected from 5 dental units using high-throughput pyrophosphate sequencing. Results: The results revealed that chlorogenic acid treatment had a significant impact on the microbial community profile in the DUWLs, with the most significant changes occurring within the first 15 days and stabilization observed in the last 30 days. The predominant genera detected in the samples were Bacteroides, Lactobacillus, Streptococcus, Methylobacterium, and Phreatobacter. Additionally, the relative abundance of certain beneficial bacteria, such as Alloprevotella, Roseburia, and Blautia, increased, while the presence of opportunistic pathogens like Mycobacteria significantly decreased. The functional prediction analysis using the KEGG database indicated a decrease in the pathogenicity of the bacterial community in the DUWLs following chlorogenic acid treatment. Discussion: This study introduces a novel approach for the prevention and treatment of infections associated with dental care.

Characterisation of highly virulent and colistin-resistant ST367-KL1 Klebsiella quasipneumoniae subsp. similipneumoniae Strain.

OBJECTIVES: To elucidate the characteristics of a colistin-resistant and hypervirulent Klebsiella quasipneumoniae subsp. similipneumoniae strain (KP8) using whole genome sequencing and various phenotypic assays. METHODS: Antimicrobial susceptibility testing was performed using broth microdilution. Whole genome sequencing and comparative genomics were utilised to elucidate genomic characteristics. Phenotypic assays to evaluate virulence factors included measurements of mucosal viscosity, biofilm production, siderophore production, infection of A549 cells, serum-killing assays, and Galleria mellonella infection models. RESULTS: Whole-genome sequencing revealed that the strain (KP8) belongs to sequence type 367 (ST367) and capsular type 1 (KL1), and it harbours several virulence genes, including regulator of mucoid phenotype (rmpA/A2), salmochelin (iroBCDN) and aerobactin (iucABCDiutA). Antibiotic susceptibility tests showed that KP8 was resistant to colistin. Genome analysis showed that the colistin resistance of KP8 might be related to amino acid insertions in pmrB (L215_D217, insL) and pagP (M1_S3, insV). Importantly, KP8 demonstrated comparable mucosal viscosity, biofilm production capacity, siderophore production levels to hvKP. Serum-killing experiments, A549 cell infection models, and G. mellonella infection models further indicated that KP8 displayed high virulence, akin to the hypervirulent strain NUTH-K2044. Notably, global genome analysis of the K. quasipneumoniae subsp. similipneumoniae strains highlighted that the ST367 lineage has a higher tendency to carry virulence-associated genes compared to other sequence types. The prevalence of virulence-associated factors concentrated within Chinese ST367 isolates reinforces this observation. CONCLUSION: These findings further enhance our understanding of the resistance and pathogenicity of ST367 K. quasipneumoniae subsp. similipneumoniae strain and also providing a broader perspective on the global epidemiological landscape.

QCR7 affects the virulence of Candida albicans and the uptake of multiple carbon sources present in different host niches.

Background: Candida albicans is a commensal yeast that may cause life-threatening infections. Studies have shown that the cytochrome b-c1 complex subunit 7 gene (QCR7) of C. albicans encodes a protein that forms a component of the mitochondrial electron transport chain complex III, making it an important target for studying the virulence of this yeast. However, to the best of our knowledge, the functions of QCR7 have not yet been characterized. Methods: A QCR7 knockout strain was constructed using SN152, and BALb/c mice were used as model animals to determine the role of QCR7 in the virulence of C. albicans. Subsequently, the effects of QCR7 on mitochondrial functions and use of carbon sources were investigated. Next, its mutant biofilm formation and hyphal growth maintenance were compared with those of the wild type. Furthermore, the transcriptome of the qcr7Δ/Δ mutant was compared with that of the WT strain to explore pathogenic mechanisms. Results: Defective QCR7 reduced recruitment of inflammatory cells and attenuated the virulence of C. albicans infection in vivo. Furthermore, the mutant influenced the use of multiple alternative carbon sources that exist in several host niches (GlcNAc, lactic acid, and amino acid, etc.). Moreover, it led to mitochondrial dysfunction. Furthermore, the QCR7 knockout strain showed defects in biofilm formation or the maintenance of filamentous growth. The overexpression of cell-surface-associated genes (HWP1, YWP1, XOG1, and SAP6) can restore defective virulence phenotypes and the carbon-source utilization of qcr7Δ/Δ. Conclusion: This study provides new insights into the mitochondria-based metabolism of C. albicans, accounting for its virulence and the use of variable carbon sources that promote C. albicans to colonize host niches.

A Complete Genome of Nocardia terpenica NC_YFY_NT001 and Pan-Genomic Analysis Based on Different Sources of Nocardia spp. Isolates Reveal Possibly Host-Related Virulence Factors.

Objective: We aimed to identify the possible virulence genes associated with Nocardia NC_YFY_NT001 isolated by ourselves and other Nocardia spp. Methods: The genome of Nocardia terpenica NC_YFY_NT001 was completed by using PacBio and Illumina platforms. A pan-genomic analysis was applied to selected complete Nocardia genomes. Results: Nocardia terpenica NC_YFY_NT001 can cause healthy mice death by tail intravenous injection. The genome of NT001 has one circular chromosome 8,850,000 bp and one circular plasmid 70,000 bp with ~68% GC content. The chromosome and plasmid encode 7914 and 80 proteins, respectively. Furthermore, a pan-genomic analysis showed a total of 45,825 gene clusters, then 304 core, 21,045 shell and 24,476 cloud gene clusters were classified using specific parameters. In addition, we found that catalases were more abundant in human isolates. Furthermore, we also found no significant differences in the MCE proteins between different strains from different sources. The pan-genomic analysis also showed that 67 genes could only be found in humoral isolates. ReX3 and DUF853 domain protein were found in all eight human isolates. The composition of unique genes in humoral isolate genomes indicated that the transcriptional regulators may be important when Nocardia invades the host, which allows them to survive in the new ecological system. Conclusion: In this study, we confirmed that NT001 could cause infected animal death, and identified many possible virulence factors for our future studies. This study also provides new insight for our further study on Nocardia virulence mechanisms.

Epidemiologic Correlation and Drug Resistance Analysis of Pathogenic Bacteria in Different Open Limb Injury External Conditions.

OBJECTIVE: To study the epidemiological correlation and drug resistance of external factors of infection caused by open injury of limbs to pathogens. METHODS: This experiment is a retrospective study. We took the geographical location and climate of Nanchang, Jiangxi Province, China as the background, analyzed 2017 strains of pathogens from 1589 patients with limb trauma infection in a University Affiliated Hospital from 2012 to 2017. Patients were divided into three groups according to the type of incision: I, In-hospital infection of clean limb incision, II, In-hospital infection with open injury, III, Community infection with open injury of the limb. Groups II and Groups III were divided into six subgroups according to the causes of trauma, including: accidents from non-motor vehicles, machinery, cutting/piercing, pedestrian injuries, struck by/against, pedal cycles, and other injuries. We found eight common pathogens of orthopedic infection, which were mainly divided into Gram-positive bacteria (G+, mainly including Staphylococcus) and Gram-negative bacteria (G-, mainly Enterobacteriaceae). The relationship between main pathogens and damage mechanism, apparent temperature and relative humidity was discussed in this study. SPSS v22.0 was used for statistical analysis of the data. Friedman's two-way ANOVA was used to analyze the difference between the injury mechanism and incidence of pathogenic bacteria. Linear regression was used to determine the trend between the incidence of major pathogens and seasonal temperature and humidity. The level of significance was set as P < 0.05. RESULTS: There was no significant difference in the distribution of pathogens between Groups II and Groups III (P>0.05). The drug resistance of Groups III was significantly higher than that of Groups II and Groups I. G+ bacteria were resistant to cephalosporin, ceftriaxone and other cephalosporins and erythromycin and other macrolides. They were sensitive to vancomycin and linezolid. G- were resistant to the first- and the second-generation cephalosporins, including cefotetan and cefazolin, and ampicillin and other penicillins, while they were sensitive to third-generation cephalosporins, such as ceftazidime, as well as to levofloxacin and other quinolones, meropenem, and other beta-lactamases. The correlation between the injury mechanism and infection of pathogenic bacteria was not significant. The monthly average apparent temperature and relative humidity were correlated with the infection rate of pathogenic bacteria. CONCLUSION: In open injury of extremities, apparent temperature and relative humidity is an important risk factor for infection by pathogenic bacteria and the drug resistance of pathogenic bacteria in out-of-hospital infection was lower than that of hospital infection.

Risk factors for methicillin-resistant Staphylococcus aureus colonization and infection in patients with human immunodeficiency virus infection: A systematic review and meta-analysis.

OBJECTIVE: To investigate the potential factors affecting methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in patients with human immunodeficiency virus (HIV) infection. METHODS: A systematic search of publications listed in electronic from inception up to August 2020 was conducted. A random-effects model was used to calculate odds ratio (OR) with 95% confidence interval (CI). RESULTS: A total of 31 studies reporting 1410 MRSA events in 17 427 patients with HIV infection were included. Previous hospitalization (OR 1.80; 95% CI 1.37, 2.36), previous antibiotic therapy (OR 2.69; 95% CI 2.09, 3.45), CD4+ count (OR 1.79; 95% CI 1.41, 2.28), Centers for Disease Control and Prevention classification of stage C (OR 2.66; 95% CI 1.80, 3.93), skin lesions (OR 2.02; 95% CI 1.15, 3.55), intravenous device use (OR 2.61; 95% CI 1.59, 4.29) and an MRSA colonization history (OR 6.30; 95% CI 2.50, 15.90) were significantly associated with an increased risk of MRSA colonization and infection. Antiretroviral therapy (OR 0.71; 95% CI 0.50, 0.99) and current antibiotic use (OR 0.13; 95% CI 0.05, 0.32) were significantly associated with a reduced risk of MRSA colonization and infection. CONCLUSION: MRSA colonization and infection in HIV-infected patients is associated with a number of risk factors.

Whole Genome Sequencing of First Janibacter indicus Isolate in China Revealed Three Unique Genomic Islands Compared with Saprophytic Strains.

INTRODUCTION: Janibacter caused bacteriemia is one of the rare infections. METHODS: In the present study, we report the first isolation of Janibacter, a rare bacterial infection, from a bacteremia patient in China. Its 16S rDNA was amplified and designated as Janibacter YFY001, which belongs to J. indicus. In addition, its genome was sequenced through combined second- and third-generation genome sequencing methods. RESULTS: Based on its genome, we identified many virulence factors, such as catalase, gelatinase, FbpABC systems, and resistant genes, among others. Interestingly, three genomic islands were found in YFY001 by comparing its genome to environmental Janibacter strains. DISCUSSION: Our study not only provides the necessary genomic information for in-depth study of Janibacter, but also provides a novel methodology for studying future cases of rare bacterial infection.

Molecular Mechanisms of Colistin Resistance in Klebsiella pneumoniae in a Tertiary Care Teaching Hospital.

Background: Over the last two decades, the prevalence of colistin resistance among the members of Enterobacteriaceae has been increasing, particularly among Klebsiella pneumoniae isolates; this limits the potential use of colistin and leads to worsened clinical outcomes. Methods: We investigated the prevalence and genetic characteristics of colistin-resistant K. pneumoniae (COLR-KP) in clinical isolates using genomic sequencing. Results: In total, 53 K. pneumoniae isolates (4.5%, 53/1,171) were confirmed as COLR-KP, of which eight isolates carried mobile colistin-resistant (mcr) gene. Although the overall prevalence rate (0.7%, 8/1,171) of mcr-like genes in clinical K. pneumoniae remained relatively low, the presence of mcr (15.1%, 8/53) among the COLR-KP isolates indicated that the mobile resistance gene was already widespread among K. pneumoniae isolates in hospital setting. We randomly selected 13 COLR-KP isolates (four mcr-bearing and nine non-mcr-bearing isolates) for whole-genome sequencing, including two pandrug-resistant and four sequence type 11 (ST11) isolates. Phylogenetic analysis revealed that all COLR-KP isolates were genetically diverse. Among the four mcr-bearing isolates, three (KP4, KP18, and KP30) were positive for mcr-1 and one (KP23) for mcr-8; none of the other mcr genes were detected. The mcr-1 in the KP4 and KP30 isolates were located in an IncX4 plasmid (approximately 33 kb) and could be successfully transferred to Escherichia coli J53AZR. In contrast, for the mcr-8-bearing plasmid in KP23 (IncFII), colistin resistance could not be transferred by conjugation. The mcr-1-producing isolate KP18 coexists a novel plasmid-carried tigecycline resistance gene tmexCD1-toprJ1. The most common chromosomal mutation associated with colistin resistance was a T246A amino acid substitution in PmrB, which was identified in most COLR-KP isolates (11/13, 84.6%). All ST11 isolates additionally had an R256G amino acid substitution. Critical virulence factors associated with hypervirulent K. pneumoniae were detected in four COLR-KP isolates; these virulence factors included aerobactin, salmochelin, and yersiniabactin. Conclusion: We found that mcr-bearing COLR-KP emerged in our hospital and was growing at an increasing rate. Simultaneous emergence of hypervirulence and colistin-tigecycline-carbapenem resistance in the epidemic clone ST11 K. pneumoniae was also observed; this highlights the significance of active and continuous surveillance.

Molecular Analysis and Antimicrobial Resistance Pattern of Tigecycline-Non-Susceptible K. pneumoniae Isolated from a Tertiary Care Hospital of East Asia.

INTRODUCTION: Tigecycline is one of the last resorts for carbapenem-resistant K. pneumoniae (CRKP) infections. Indeed, tigecycline-non-susceptible K. pneumoniae (TNSKP) strains are increasingly treated with the use of tigecycline. In this study, we attempted to better understand their epidemiological trends and characteristics. K. pneumoniae were collected from 2017 to 2020 at the First Affiliated Hospital of Nanchang University. METHODS: Thirty-four TNSKP strains were selected during the study period, all of which were analyzed using antimicrobial susceptibility testing, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). PCR and DNA sequencing were performed for the detection of ß-lactamase genes and carbapenemase genes, and the mutation analysis of tet(A), tet(X), tet(L), tet(M), rpsJ, ramR, and oqxR, which are related to tigecycline resistance. Virulence gene and capsular genotype testing were conducted to identify whether the TNSKP strains were hypervirulent Klebsiella pneumoniae. RESULTS: An epidemiology analysis showed that Klebsiella pneumoniae carbapenemase-2 (KPC-2) was the predominant carbapenemase in tigecycline non-susceptible carbapenem-resistant K. pneumoniae (TNSCRKP) (96.7%), and the dominant clone type was ST11-K14K64 (82.4%). Among them, 55.9% (19/34) of strains were from each department of ICU, particularly EICU and neurosurgery ICU. In order to further understand the molecular mechanisms of the TNSKP, a polymerase chain reaction of the resistant determinants was carried out. The results detected many tigecycline-resistant genes, such as tet(A) (97.1%), tet(X) (17.6%), rpsJ (97.1%), and ramR (8.8%). CONCLUSION: As the results of this study reveal, we should take effective measures to control the increase in TNSKP.

Molecular Epidemiology, Antifungal Susceptibility, and Virulence Evaluation of Candida Isolates Causing Invasive Infection in a Tertiary Care Teaching Hospital.

Background: The incidence of invasive candidiasis is increasing worldwide. However, the epidemiology, antifungal susceptibility, and virulence of Candida spp. in most hospitals remain unclear. This study aimed to evaluate invasive candidiasis in a tertiary care hospital in Nanchang City, China. Methods: MALDI-TOF MS and 18S rDNA ITS sequencing were used to identify Candida strains. Randomly amplified polymorphic DNA analysis was used for molecular typing; biofilm production, caseinase, and hemolysin activities were used to evaluate virulence. The Sensititre™ YeastOne YO10 panel was used to examine antifungal susceptibility. Mutations in ERG11 and the hotspot regions of FKS1 of drug-resistant strains were sequenced to evaluate the possible mechanisms of antifungal resistance. Results: We obtained 110 Candida strains, which included 40 Candida albicans (36.36%), 37 C. parapsilosis (33.64%), 21 C. tropicalis (19.09%), 9 C. glabrata (8.18%), 2 C. rugose (1.82%), and 1 C. haemulonii (0.91%) isolates. At a limiting point of 0.80, C. albicans isolates could be grouped into five clusters, C. parapsilosis and C. tropicalis isolates into seven clusters, and C. glabrata isolates into only one cluster comprising six strains by RAPD typing. Antifungal susceptibility testing revealed that the isolates showed the greatest overall resistance against fluconazole (6.36%), followed by voriconazole (4.55%). All C. albicans and C. parapsilosis isolates exhibited 100% susceptibility to echinocandins (i.e., anidulafungin, caspofungin, and micafungin), whereas one C. glabrata strain was resistant to echinocandins. The most common amino acid substitutions noted in our study was 132aa (Y132H, Y132F) in the azole-resistant strains. No missense mutation was identified in the hotpot regions of FKS1. Comparison of the selected virulence factors detectable in a laboratory environment, such as biofilm, caseinase, and hemolysin production, revealed that most Candida isolates were caseinase and hemolysin producers with a strong activity (Pz < 0.69). Furthermore, C. parapsilosis had greater total biofilm biomass (average Abs620 = 0.712) than C. albicans (average Abs620 = 0.214, p < 0.01) or C. tropicalis (average Abs620 = 0.450, p < 0.05), although all C. glabrata strains were either low- or no-biofilm producers. The virulence level of the isolates from different specimen sources or clusters showed no obvious correlation. Interesting, 75% of the C. albicans from cluster F demonstrated azole resistance, whereas two azole-resistant C. tropicalis strains belonged to the cluster Y. Conclusion: This study provides vital information regarding the epidemiology, pathogenicity, and antifungal susceptibility of Candida spp. in patients admitted to Nanchang City Hospital.

Drug resistance of pathogens causing nosocomial infection in orthopedics from 2012 to 2017: a 6-year retrospective study.

BACKGROUND: Hospital-acquired infections (HAIs) are an emerging global problem that increases in-hospital mortality, length of stay, and cost. We performed a 6-year retrospective study to provide valuable insight into appropriate antibiotic use in HAI cases. We also aimed to understand how hospitals could reduce pathogen drug resistance in a population that overuses antibiotics. METHODS: All data (2012-2017) were obtained from the hospital information warehouse and clinical microbiology laboratory. RESULTS: We isolated 1392 pathogen strains from patients admitted to the orthopedics department during 2012-2017. Escherichia coli (14.7%, 204/1392), Enterobacter cloacae (13.9%, 193/1392), and Staphylococcus aureus (11.3%, 157/1392) were the most common pathogens causing nosocomial infections. The dominant Gram-negative bacterium was E. coli, with high resistance to ampicillin, levofloxacin, cotrimoxazole, gentamicin, and ciprofloxacin, in that order. E. coli was least resistant to amikacin, cefoperazone-sulbactam. The most dominant Gram-positive bacterium was S. aureus, highly resistant to penicillin and ampicillin, but not resistant to fluoroquinolones and cotrimoxazole. Analysis of risk factors related to multidrug-resistant bacteria showed that patients with open fractures (Gustillo III B and IIIC) were significantly more susceptible to methicillin-resistant S. aureus infections (p < 0.05). Additionally, extended-spectrum ß-lactamase-producing E. coli infections occurred significantly more often in patients with degenerative diseases (p < 0.05). Elderly patients tended to be more susceptible to multidrug-resistant bacterial infections, but this outcome was not statistically significant. CONCLUSIONS: Antimicrobial resistance is a serious problem in orthopedics. To effectively control antimicrobial resistance among pathogens, we advocate extensive and dynamic monitoring of MDR bacteria, coupled with careful use of antibiotics.

Treatment with the traditional Chinese medicine BuYang HuanWu Tang induces alterations that normalize the microbiome in ASD patients.

Autism spectrum disorders (ASDs) are prevalent neurobiological conditions with complicated causes worldwide. Increasing researcher awareness of ASD and accumulated evidence suggest that the development of ASD may be strongly linked to the dysbiosis of the gut microbiota. In addition, most of the current studies have compared autistic children and neurotypical children or have compared ASD patients before and after antibiotic treatment. Treatment of autism with traditional Chinese medicine (TCM) has increasingly been promoted, but the relationship between its efficacy and intestinal flora has rarely been reported. Under the premise that treatment with the TCM BuYang HuanWu Tang is effective, we conducted a comparative bioinformatics analysis to identify the overall changes in gut microbiota in relation to ASD by comparing the intestinal flora before and after treatment with TCM and contrasting the intestinal flora with that of healthy controls. At the phylum level, Proteobacteria showed a significant increase in children with ASD, which may be a signature of dysbiosis in the gut microbiota. At the genus level, Blautia, Coprococcus 1, the Lachnospiraceae family, and the Ruminococcaceae family were found at the lowest levels of relative abundance in children with ASD, whereas the abundances of Escherichia-Shigella, Klebsiella, and Flavonifractor were significantly increased compared with those in the healthy control group. In sum, this study characterized the alterations of the intestinal microbiome in children with ASD and its normalization after TCM treatment (TCMT), which may provide novel insights into the diagnosis and therapy of ASD.

Epidemiology and Drug Resistance Analysis of Mixed Infection in Orthopedic Surgical Sites.

Background: Infection, including mixed infection, is not uncommon in orthopedic surgical incision. This study aimed to investigate the epidemiology and drug resistance of mixed infections after orthopedic surgical procedures. Methods: We retrospectively analyzed 533 orthopedic surgical site infections (SSIs) in a university hospital from 2012 to 2017. Eighty-six patients (218 strains) with bacterial culture results showing more than one strain were screened to explore their epidemiology and drug resistance. Results: Of 218 bacterial strains, 2-7 bacterial infections were noted in each wound. Most infections were caused by two kinds of bacteria (65.1%). The number of infections decreased with increased number of strains. The combinations of pathogenic micro-organisms were all gram-negative, 55.81%; gram-positive and gram-negative, 30.23%; all gram-positive, 12.79%; and gram-positive and fungi, 1.16%. Their resistance is consistent with the bacterial resistance of 447 cases of single bacterial SSI during the same period. Hospitalization duration was longer (9.8-20.6 d). Conclusion: Our study shows no significant changes in epidemiology and drug resistance caused by mixed infections in the orthopedic surgical site because of coordination and competition among micro-organisms. These bacteria are difficult to control, leading to extended hospitalization. Antibiotic agents should be chosen strictly according to drug sensitivity, and ineffective antibiotic agents must be avoided.

Novel long non-coding RNA AV310809 promotes TGF-ß1 induced epithelial-mesenchymal transition of human peritoneal mesothelial cells via activation of the Wnt2/ß-catenin signaling pathway.

Peritoneal fibrosis (PF) is a crucial cause of the loss of peritoneal function in patients with peritoneal dialysis. To better understand the underlying mechanism of PF, we selected AV310809, which is one of the most highly upregulated lncRNA in fibrotic peritoneal tissue, for functional analysis. We used co-expression analysis to explore the potential relationship between AV310809 and coding genes. qPCR, WB and IF were applied to evaluate the expression and localization of AV310809, epithelial markers and proteins involved in the Wnt2/ß-catenin signaling pathway. The interaction between AV310809 and ß-catenin was examined using an RNA pulldown assay. The expression level of AV310809 was upregulated in fibrotic peritoneum and TGF-ß1 induced EMT in HPMCs. Ectopic overexpression of AV310809 promoted EMT and activated the Wnt2/ß-catenin signaling pathway. Furthermore, we demonstrated that AV310809 could interact with ß-catenin and blocking ß-catenin inhibited the augmentation of EMT by AV310809. These findings indicated that AV310809 promoted TGF-ß1-induced EMT in HPMCs through the activation of the Wnt2/ß-catenin signaling pathway, possibly by targeting ß-catenin. We suggest that AV310809 may be a new therapeutic target for the management of peritoneal dialysis-associated PF.

A Novel Pan-Genome Reverse Vaccinology Approach Employing a Negative-Selection Strategy for Screening Surface-Exposed Antigens against leptospirosis.

Reverse vaccinology (RV) has been widely used for screening of surface-exposed proteins (PSEs) of important pathogens, including outer membrane proteins (OMPs), and extracellular proteins (ECPs) as potential vaccine candidates. In this study, we applied a novel RV negative strategy and a pan-genome analysis for screening of PSEs from 17 L. interrogans strains covering 11 predominately epidemic serovars and 17 multilocus typing (MLST) sequence types (STs) worldwide. Our results showed, for instance, out of a total of 633 predicted PSEs in strain 56601, 92.8% were OMPs or ECPs (588/633). Among the 17 strains, 190 core PSEs, 913 dispensable PSEs and 861 unique PSEs were identified. Of the 190 PSEs, 121 were further predicted to be highly antigenic and thus may serve as potential vaccine candidates against leptospirosis. With the exception of LipL45, OmpL1, and LigB, the majority of the 121 PSEs were newly identified antigens. For example, hypothetical proteins BatC, LipL71, and the OmpA family proteins sharing many common features, such as surface-exposed localization, universal conservation, and eliciting strong antibody responses in patients, are regarded as the most promising vaccine antigens. Additionally, a wide array of potential virulence factors among the predicted PSEs including TonB-dependent receptor, sphingomyelinase 2, leucine-rich repeat protein, and 4 neighboring hypothetical proteins were identified as potential antigenicity, and deserve further investigation. Our results can contribute to the prediction of suitable antigens as potential vaccine candidates against leptospirosis and also provide further insights into mechanisms of leptospiral pathogenicity. In addition, our novel negative-screening strategy combined with pan-genome analysis can be a routine RV method applied to numerous other pathogens.

Association of genetic polymorphisms at 1q22 but not 10q23 with gastric cancer in a southern Chinese population.

OBJECTIVE: Data from a recent genome-wide association studiesy of gastric cancer (GC) and oesophageal squamous cell carcinoma in Chinese living in the Taihang Mountains of north-central China suggest that 1q22 and 10q23 are susceptibility-associated regions for GC. However, this has not been confirmed in southern Chinese populations. The aim of this study was to investigate whether these polymorphisms at 1q22 and 10q23 are associated with the risk of GC in a southern Chinese population. METHODS: We selected seven top significant associated single nucleotide polymorphisms (SNPs) at 1q22 and 10q23 and conducted a population-based case- control study in a southern Chinese population. Genotypes were determined using MassARRAYTM system (Sequenome, San Diego, CA). RESULTS: Two SNPs at 1q22, rs4072037 and rs4460629, were significantly associated with a reduced risk of GC, best fitting the dominant genetic model. Logistic regression models adjusted for age and sex showed that rs4072037 AG and GG (OR=0.64, P=0.017, compared with AA) and rs4460629 CT and TT (OR=0.54, P=0.0016, compared with TT) significantly reduced the risk of GC. However, no significant results for the five SNPs at 10q23 were obtained in this study. CONCLUSION: These outcomes indicate that 1q22 is associated with GC susceptibility in this southern Chinese population, while an association for the locus at 10q23 was not confirmed.

Association of 10q23 with colorectal cancer in a Chinese population.

Recently, a genome-wide association study of gastric cancer (GC) reported the significant association of seven genetic variants (rs4072037 and rs4460629 on 1q22; rs753724, rs11187842, rs3765524, rs2274223, and rs3781264 on 10q23) with GC in a Chinese population. These findings were confirmed in a subsequent independent study. However, it remains unknown whether these loci are associated with an increased risk of colorectal cancer (CRC). This study was to test whether the seven single nucleotide polymorphisms (SNPs) associated with GC were also associated with CRC in a Chinese population. The seven SNPs were genotyped using MassARRAY system. Allelic, genotypic, and haplotypic associations of the SNPs with CRC were investigated using χ(2) tests and logistic regression analysis. The SNPs rs3765524 and rs2274223, located on 10q23, were found to have significant protective effects against CRC, with equal odds ratios per allele. The two SNPs located on 1q22 (rs4072037 and rs4460629) showed a weak association with CRC. No significant association was identified with CRC for the remaining three SNPs located on 10q23 (rs753724, rs11187842, and rs3781264). These results suggest that rs3765524 and rs2274223 on 10q23 are associated with a protective effect against CRC in a Chinese population.

Single-nucleotide polymorphism associations for colorectal cancer in southern chinese population.

OBJECTIVE: Genome-wide association studies (GWAS) have identified 11 loci that influence the risk of developing colorectal cancer (CRC). Given that these studies were conducted in European Caucasian populations, it is not clear whether the results are relevant for populations with different ethnicities. The aim of this study was to examine these associations in a southern Chinese population. METHODS: Eleven single-nucleotide polymorphisms (SNPs), rs12701937, rs16892766, rs7014346, rs6983267, rs719725, rs10795668, rs3802842, rs4444235, rs9929218, rs10411210, and rs961253, were genotyped in 229 CRC patients and 267 controls using the MassArray SNP genotyping system. RESULTS: Evidence of an association with CRC was found for four of the 11 loci. The strongest associations were with rs4444235 and rs961253, with significant odds ratios close to those reported in previous GWAS. Among these four loci, rs719725 and rs4444235 were significantly associated with female gender, rs3802842, rs961253, and rs4444235 with early disease onset, and rs3802842 with later disease onset. However, no associations with CRC risk were detected for six other loci (rs9929218, rs10411210, rs12701937, rs7014346, rs6983267, and rs10795668), and one SNP, rs16892766, was not polymorphic in any of the study participants. CONCLUSION: The rs4444235 and rs961253 loci are strongly associated with the risk of CRC in southern Chinese.

A risk-associated single nucleotide polymorphism of SMAD7 is common to colorectal, gastric, and lung cancers in a Han Chinese population.

SMAD7 has been demonstrated to antagonize TGF-ß-mediated fibrosis, carcinogenesis, and inflammation. Two previous genome-wide association studies identified three single nucleotide polymorphisms (SNPs) (rs4939827, rs12953717 and rs4464148) in SMAD7 to be associated with colorectal cancer in a Western population. We conducted the first case-control study in a Han Chinese population to explore the associations between these three SNPs and colorectal, gastric, and lung cancers. Of the three SNPs, only rs12953717 was strongly associated with the three types of cancer, fitting the overdominant model. Compared with the CC/TT (CC combined with TT) genotype, the adjusted odds ratios for the CT genotype were 2.002 (95% CI, 1.250-3.207, P = 0.004), 1.678 (95% CI, 1.048-2.689, P = 0.031), 3.825 (95% CI, 2.310-6.335, P < 1 × 10(-4)), and 2.294 (95% CI, 1.537-3.343, P < 1 × 10(-4)), respectively, for colorectal, gastric, lung, and combined cancers. These outcomes suggest that rs12953717 is a common risk marker of these three types of cancer in the Han Chinese.

Genetic Variants in MMP9 and TCF2 Contribute to Susceptibility to Lung Cancer.

OBJECTIVE: The Wnt signaling pathway is crucial for pulmonary development and differentiation; dysregulation of the Wnt signaling pathway may impair lung function. Indeed, single nucleotide polymorphisms (SNPs) of Wnt pathway-related genes have been suggested as risk factors for certain types of cancers. In this study, we aimed to evaluate the influence of SNPs in Wnt-related genes (TCF2, MMP9) on susceptibility to lung cancer. METHODS: Polymorphisms of TCF2 rs4430796, MMP9 rs2250889, and MMP9 rs17576 were studied in Han Chinese subjects, including 135 patients with lung cancer and 176 controls, using the Sequenom MassARRAY platform. The association of genotypes with susceptibility to lung cancer was analyzed using odds ratio (OR), with 95% confidence interval (95% CI) and χ(2). RESULTS: The three SNPs (rs4430796, rs2250889, and rs17576) were found to be significantly associated with an increased risk of lung cancer. The AA genotype and AG+AA genotype of rs4430796 showed a significantly increased susceptibility to lung cancer compared with the GG genotype (adjusted OR=6.03, 95% CI: 1.30-28.09, P=0.022; 5.55, 95% CI: 1.20-25.58, P=0.028). Compared with the rs17576 GG genotype, the AG and AG+AA genotypes were also associated with a significant risk (adjusted OR=2.65, 95% CI: 1.60-4.37, P≤0.001; 2.57, 95% CI: 1.59-4.19, P≤0.001) whereas the rs2250889 CG and CG+GG genotypes had 2.97-fold (95% CI: 1.81-4.85; P≤0.001) and 2.80-fold increased associations with lung cancer (95% CI: 1.73-4.54; P≤0.001), respectively, compared with the rs2250889 CC genotype. Furthermore, the association of rs4430796 with lung cancer became insignificant (P>0.05) after adjusting for gender and rs2250889. CONCLUSION: The three SNPs may play a role in the predisposition of members of the Han Chinese population to lung cancer.