Browsing by Author "Zhang, Kunyan"

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    A Caenorhabditis elegans Host Model Correlates with Invasive Disease Caused by Staphylococcus aureus Recovered during an Outbreak in Neonatal Intensive Care
    (2012-01-01) Wu, Kaiyu; Simor, Andrew E; Vearncombe, Mary; McClure, Jo-Ann; Zhang, Kunyan
    BACKGROUND: Caenorhabditis elegans has previously been used as a host model to determine the virulence of clinical methicillin-resistant Staphylococcus aureus isolates. In the present study, methicillin-susceptible S aureus (MSSA) strains associated with an outbreak in a neonatal intensive care unit (NICU) were investigated using the C elegans model.METHODS: Two distinct outbreak clones, MSSA type-C and MSSA type-G, were identified by pulsed-field gel electrophoresis in a MSSA outbreak during a seven-month period in the NICU of the Sunnybrook Health Sciences Centre (Toronto, Ontario). MSSA type-C was associated with severe infection, while type-G was associated with less invasive disease. Four representative type-C isolates, three type-G and three infant-colonized isolates unrelated to the outbreak, were sent to Calgary (Alberta), for the double-blinded virulence tests in the C elegans host model and for further molecular characterization.RESULTS: The invasive outbreak strains (type-C) demonstrated highly nematocidal activity, the noninvasive outbreak strains (type-G) an intermediate virulence, and the outbreak-unrelated colonization isolates demonstrated avirulence or low virulence in the C elegans model, with mean killing rates of 93.0%, 61.0% and 14.4% by day 9, respectively, for these three group strains. Different group MSSA strains had their own unique genetic profiles and virulence gene profiles, but all isolates within the same group (type-C or type-G) shared identical genetic characteristics and virulence gene patterns.CONCLUSIONS: The present blinded evaluation demonstrated that the nematocidal activities of MSSA strains correlated well with the clinical manifestation in an MSSA outbreak in the NICU, supporting C elegans as a robust host model to study the pathogenesis of S aureus.
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    A New Method for Assessing Tissue Alignment using Clinical MRI in Multiple Sclerosis
    (2017) Sharma, Shrushrita; Zhang, Kunyan; Pike, Bruce; Dunn, Jeffery Frank
    Changes in the alignment of white matter tracts are common in many neurological disorders such as multiple sclerosis (MS). Currently advanced MRI methods including diffusion-weighted imaging is the mainstay in assessing tissue coherency and anisotropy. In this thesis, I have implemented and verified a novel image-processing method for this purpose using conventional MRI. This is done based on Fourier transform power spectrum. Outcomes were evaluated in 3 steps: 1) testing feasibility using brain areas with highly aligned nerve fiber tracks in T2- weighted MRI; 2) confirming pathological relevance using postmortem brain sample; and 3) assessing utility by comparing with diffusion tensor imaging. To improve the accuracy of comparison with pathology, I have also conducted quantitative histology besides traditional analysis of the staining density of myelin and axons. The results suggest that advanced analysis of clinical MRI may provide valuable information as powerful as advanced MRI to enhance the measurement of tissue property.
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    Assessment of virulence diversity of methicillin-resistant Staphylococcus aureus strains with a Drosophila melanogaster infection model
    (BioMed Central, 2012-11-23) Zhang, Kunyan; Wu, Kaiyu; Conly, John; Surette, Michael G.; Sibley, Christopher; Elsayed, Sameer
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    Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia without Evidence of Antecedent Viral Upper Respiratory Infection
    (2014-01-01) Toro, Cristina Moran; Janvier, Jack; Zhang, Kunyan; Fonseca, Kevin; Gregson, Dan; Church, Deirdre; Laupland, Kevin; Rabin, Harvey; Elsayed, Sameer; Conly, John
    BACKGROUND: USA300 community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) strains causing necrotizing pneumonia have been reported in association with antecedent viral upper respiratory tract infections (URI).METHODS: A case series of necrotizing pneumonia presenting as a primary or coprimary infection, secondary to CA-MRSA without evidence of antecedent viral URI, is presented. Cases were identified through the infectious diseases consultation service records. Clinical and radiographic data were collected by chart review and electronic records. MRSA strains were isolated from sputum, bronchoalveolar lavage, pleural fluid or blood cultures and confirmed using standard laboratory procedures. MRSA strains were characterized by susceptibility testing, pulsed-field gel electrophoresis, spa typing, agr typing and multilocus sequence typing. Testing for respiratory viruses was performed by appropriate serological testing of banked sera, or nucleic acid testing of nasopharyngeal or bronchoalveloar lavage specimens.RESULTS: Ten patients who presented or copresented with CA necrotizing pneumonia secondary to CA-MRSA from April 2004 to October 2011 were identified. The median length of stay was 22.5 days. Mortality was 20.0%. Classical risk factors for CA-MRSA were identified in seven of 10 (70.0%) cases. Chest tube placement occurred in seven of 10 patients with empyema. None of the patients had historical evidence of antecedent URI. In eight of 10 patients, serological or nucleic acid testing testing revealed no evidence of acute viral coinfection. Eight strains were CMRSA-10 (USA300). The remaining two strains were a USA300 genetically related strain and a USA1100 strain.CONCLUSION: Pneumonia secondary to CA-MRSA can occur in the absence of an antecedent URI. Infections due to CA-MRSA are associated with significant morbidity and mortality. Clinicians need to have an awareness of this clinical entity, particularly in patients who are in risk groups that predispose to exposure to this bacterium.
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    Comprehensive Strategy to Decolonize Methicillin-Resistant Staphylococcus aureus in the Outpatient Setting: a Randomized Controlled Study
    (2013-10-03) Kim, Joseph; Henderson, Elizabeth; Conly, John; Louie, Thomas; Sauve, Reg; Zhang, Kunyan
    The objective of this study was to examine the efficacy of a comprehensive decolonization treatment in reducing methicillin-resistant Staphylococcus aureus (MRSA) carriage among an outpatient population. Patients colonized with MRSA were randomized to receive pharmacological decolonization treatment or no treatment. The primary outcome was detection of MRSA at 3 months. Occurrence of MRSA infection was assessed at 6 months. Molecular analyses were performed on all MRSA isolates. Of 205 patients, 15 (7%) were enrolled into the study (9 treatment; 6 control). At 3 months, 4/8 (50%) in the treatment group had eradication and none in the control group (0/4, 0%). Infection occurred in 5 patients (3 treatment; 2 control). All of the MRSA isolates were community-associated MRSA strain types with USA300 accounting for 87%. Among persistent CA-MRSA carriers, our decolonization treatment was well tolerated. However, enrollment was limited. Future studies with different enrollment strategies are required.
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    Development of tissue directionality-based measures of demyelination and remyelination for multiple sclerosis using structure tensor analysis
    (2014-10-10) Kamalpour-Ansari, Mohammad hadi; Zhang, Kunyan; Yong, V. Wee
    Changes in myelin integrity are key characteristics of many diseases including multiple sclerosis. The goal of this project was to evaluate the feasibility of structure tensor analysis, a potentially new measure of tissue directionality, to measure myelin health. Using histology and MR images obtained from a lysolecithin model of demyelination and remyelination, I quantified the coherency (anisotropy), energy (organization), and entropy (heterogeneity) of white matter in mouse spinal cords with different myelin integrity and found that demyelinated tissue had lower coherency and energy but higher entropy than tissues with intact myelin. I also tested the robustness of this technique to the change in image size in MRI and showed its practical feasibility. My findings suggest that tissues with better myelin integrity have greater alignment and anisotropy. Structure tensor analysis may have the potential to evaluate de- and re-myelination in patients with multiple sclerosis and similar disorders. Further validation is warranted.
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    In Vivo Imaging of Neutrophil Responses to Localized S. aureus Infection
    (2013-12-13) Harding, Mark; Kubes, Paul; Zhang, Kunyan
    Methicillin-resistant Staphylococcus aureus (MRSA) is a highly virulent, multidrug –resistant pathogen responsible for the majority of soft tissue infections. The role of neutrophils in S. aureus soft tissue infections is currently unclear. The objective of this thesis was to characterize early neutrophil recruitment to a localized MRSA infection. Using spinning disk confocal microscopy, we developed a mouse model to visualize the behaviour of neutrophils in the skin following the introduction of an agarose bead embedded with GFP-expressing MRSA. We observed significant neutrophil recruitment not only in the venules but also in the capillaries, which we showed to be mediated by the β2 and α4 integrins. Blocking these integrins in mouse models increased capillary perfusion, reduced cell death at early time points, and altered lesion size during infection. Understanding the contribution of neutrophils in MRSA soft tissue infection will help to elucidate novel therapeutic targets in these infections.
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    Methicillin-Resistant Staphylococcus aureus Carriage among Students at a Historically Black University: A Case Study
    (2013-01-20) Shen, Hua; Akoda, Eyitayo; Zhang, Kunyan
    Background. Black people in the USA is afflicted with a higher rate of methicillin-resistant Staphylococcus aureus (MRSA) infection. This study determined the prevalence of MRSA carriage among black college students at a university setting. Methods. Hand and nasal swabs were collected and screened for MRSA by mannitol fermentation, coagulase, and DNase activities and their resistance to oxacillin. MRSA isolates were analyzed for antimicrobial resistance pattern, genetic profile for staphylococcal cassette chromosome mec (SCCmec) type, pulsed-field type, multilocus sequence type (ST), and the presence of Panton-Valentine leukocidin (PVL) gene. Results. MRSA was isolated from 1 of the 312 (0.3%) hand swabs and 2 of the 310 (0.65%) nasal swabs, respectively. All isolates lack multidrug resistance and have type IV SCCmec, characteristic of community-associated MRSA. These isolates were a ST8-MRSA-IVa-PVL(+) (USA300 strain), a ST8-MRSA-IVb-PVL(−), and a new MLST, ST2562-MRSA-IV-PVL(−), identified in this study. These isolates were thus not transmitted among students. Conclusion. We found a low rate of MRSA carriage among students in a black university. Our finding highlights the need of future study which involves multiinstitutions and other ethnic group to assess the association of black race with MRSA carriage.
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    Microbiological and Molecular Identification and Characterization of Avian Pathogenic Escherichia coli from Poultry Farms, Alberta
    (2024-01) Wang, Yanqi; Niu, Dongyan; Niu, Dongyan; Abdul-Careem, Mohamed Faizal; Fairbrother, John; Zhang, Kunyan
    Avian pathogenic Escherichia coli (APEC) is the etiological agent of avian colibacillosis, leading to significant economic losses in Canada and elsewhere. Avian fecal E. coli (AFEC) is considered to serve as a potential reservoir for APEC given shared genetic features. This study aimed to profile phenotypic and genotypic features of causative APEC in Alberta. Here, 100 APEC isolates from diseased and dead chickens (broiler and layer) and turkeys from 45 farms collected between 2021 and 2023 were subjected to serogroup typing, APEC-associated virulence gene (VG) profiling, antimicrobial susceptibility testing, multilocus sequence typing, and phylogenetic analysis. In addition, 121 AFEC isolates from five layer flocks were collected to investigate APEC-associated VG carriage in healthy birds. Furthermore, genetic similarity between 22 AFEC strains identified as potential APEC (poAPEC) and APEC strains was assessed through phylogenetic analysis. We identified 27 serogroups, 38 known and two novel sequence types (STs), and varied VG distribution across APEC isolates from chickens and turkeys. Interestingly, variations in VG among AFEC strains were found across distinct egg laying stages or housing systems. Antimicrobial resistance (AMR) genes, especially extended-spectrum beta-lactamase genes were detected in APEC and poAPEC strains across all poultry species. Moreover, phylogenetic analysis revealed close clonal relationships among APEC and poAPEC strains. Notably, we identified a poAPEC isolate that shared ST155 and VGs with an APEC strain. This study is the first to report the characteristics of APEC and poAPEC isolates that cause or potentially cause colibacillosis morbidity and mortalities in chickens and turkeys in Alberta. A variety of APEC phenotypes and genotypes can lead to colibacillosis in poultry farms and may originate from the commensal E. coli found in the gastrointestinal tract of birds.
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    Prevalence of USA300 Colonization or Infection and Associated Variables During an Outbreak of Community-Associated Methicillin-Resistant Staphylococcus aureus in a Marginalized Urban Population
    (2007-01-01) Gilbert, Mark; MacDonald, Judy; Louie, Marie; Gregson, Dan; Zhang, Kunyan; Elsayed, Sameer; Laupland, Kevin; Nielsen, Diane; Wheeler, Virginia; Lye, Tara; Conly, John
    BACKGROUND: In 2004, an outbreak of the USA300 strain of methicillin-resistant Staphylococcus aureus (MRSA) was identified in persons with histories of homelessness, illicit drug use or incarceration in the Calgary Health Region (Calgary, Alberta). A prevalence study was conducted to test the hypotheses for factors associated with USA300 colonization or infection.METHODS: Participants were recruited at sites accessed by this marginalized population. Health care staff administered a questionnaire and collected crack pipes and nasal, axillary and skin infection swabs. Pipes and swabs were cultured according to standard techniques. MRSA isolates were further characterized by polymerase chain reaction (mecA, Panton-Valentine leukocidin and Staphylococcal cassette chromosome mec) and typing methods (pulsed-field gel electrophoresis, staphylococcal protein A typing and multilocus sequence typing). Colonization or infection was determined by having any one of nasal, axillary, skin infection or pipe swabs positive for USA300. Colonized participants had one or more nasal, axillary or pipe swab positive for USA300; infected participants had one or more skin infection swab positive for USA300.RESULTS: The prevalence of USA300 colonization or infection among 271 participants was 5.5% (range 3.1% to 9.0%). USA300 cases were more likely to report manipulation of skin infections (OR 9.55; 95% CI 2.74 to 33.26); use of crack pipes was not significant despite identification of the USA300 strain on two of four crack pipes tested. USA300 cases were more likely to report drug use between sex trade workers and clients (OR 5.86; 95% CI 1.63 to 21.00), and with casual sex partners (OR 5.40; 95% CI 1.64 to 17.78).CONCLUSION: Ongoing efforts to promote the appropriate treatment of skin infections in this population are warranted. The association of USA300 colonization or infection and drug use with sexual partners suggest a role for sexual transmission of the USA300 strain of MRSA.
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    The Role of Staphylococcal Protein A (SPA) in the Virulence of Staphylococcus aureus Infections.
    (2014-05-05) Khateb, Aiah; Zhang, Kunyan
    Staphylococcus aureus infections have spread globally and caused significant morbidity and mortality. Previous studies have indicated several functions that Staphylococcal Protein A (SPA) plays to enhance S. aureus virulence. To evaluate the role of SPA in S. aureus with respect to virulence and other biological functions, the chimeric clones were constructed by replacing the spa gene of a high-virulence S. aureus strain with the spa from a non/low-virulence strain, and vice versa. Three representative MRSA strains, a high-virulence CA-MRSA strain USA300 (spa t008), a typically low-virulence hospital-associated MRSA strain CMRSA6 (spa t037) and an avirulent colonization strain M92 (non-typeable spa) with different genetic backgrounds (ST8, ST239 and ST239, respectively) were selected. Expression of the spa gene was confirmed by western blot. The chimeric clone was evaluated by its growth curve, immunoglobulin (IgG) binding capacity, biofilm formation, and virulence using the Caenorhabditis elegans nematode infection model, and compared with the wild type (WT) donor strains. The chimeric clone USA300spa▲:: CMRSA6 spa, which had the background of a high virulence strain USA300 with the native spa gene being replaced by the spa gene of a low virulence strain CMRSA6, showed a slower growth rate, and a significantly decreased SPA expression with a 24-fold dramatic reduction in SPA IgG-Fc binding capacity. There was a 3.4-fold increase in the biofilm formation and a 62% reduction in the nematocidal activity, when compared to the parent strain WT-USA300. The other two opposite chimeric clones (M92 spa▲::USA300 spa and M92spa▲::CMRSA6spa) were constructed from an avirulent colonization strain M92, with the native spa gene being replaced with the spa genes of a high virulence strain USA300 and a low virulence strain CMRSA6, respectively. Both chimeric clones (M92 spa▲::USA300 spa and M92spa▲::CMRSA6spa) showed slight changes in growth rates, significantly increased SPA expression with 1.6- and 0.7-fold increase in SPA IgG-Fc binding capacity, respectively. No significant change was observed in the biofilm formation and the nematocidal activity of both chimeric clones when compared to the parent strain WT-M92. In conclusion, replacing the spa gene of S. aureus strain altered its biological characteristics, behavior and virulence. This study resultssuggests that spa plays an important role in the virulence and pathogenicity of S. aureus infections.