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359 results on '"Xiong, Yan Q."'

51. Role of mgrA and sarA in the methicillin-resistant Staphylococcus aureus autolysis and resistance to cell wall-active antibiotics

Author

Trotonda, Maria Pilar, Xiong, Yan Q., Memmi, Guido, Bayer, Arnold S., and Cheung, Ambrose L.

Subjects
Staphylococcus aureus infections -- Care and treatment, Staphylococcus aureus infections -- Research, Bacterial cell walls -- Physiological aspects, Bacterial cell walls -- Research, Phagocytosis -- Physiological aspects, Phagocytosis -- Research, Cellular control mechanisms -- Research, Health
Published
2009

55. In vitro and in vivo activity of d-serine in combination with β-lactam antibiotics against methicillin-resistant Staphylococcus aureus

Author

Wang, Qing, primary, Lv, Yuemeng, additional, Pang, Jing, additional, Li, Xue, additional, Lu, Xi, additional, Wang, Xiukun, additional, Hu, Xinxin, additional, Nie, Tongying, additional, Yang, Xinyi, additional, Xiong, Yan Q., additional, Jiang, Jiandong, additional, Li, Congran, additional, and You, Xuefu, additional

Published
2019
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61. Impact of Vancomycin on sarA-Mediated Biofilm Formation: Role in Persistent Endovascular Infections Due to Methicillin-Resistant Staphylococcus aureus

Author

Abdelhady, Wessam, Bayer, Arnold S., Seidl, Kati, Moormeier, Derek E., Bayles, Kenneth W., Cheung, Ambrose, Yeaman, Michael R., Xiong, Yan Q., Abdelhady, Wessam, Bayer, Arnold S., Seidl, Kati, Moormeier, Derek E., Bayles, Kenneth W., Cheung, Ambrose, Yeaman, Michael R., and Xiong, Yan Q.

Abstract

Background. Staphylococcus aureus is the most common cause of endovascular infections. The staphylococcal accessory regulator A locus (sarA) is a major virulence determinant that may potentially impact methicillin-resistant S. aureus (MRSA) persistence in such infections via its influence on biofilm formation. Methods. Two healthcare-associated MRSA isolates from patients with persistent bacteremia and 2 prototypical community-acquired MRSA strains, as well as their respective isogenic sarA mutants, were studied for in vitro biofilm formation, fibronectin-binding capacity, autolysis, and protease and nuclease activities. These assays were done in the presence or absence of sub-minimum inhibitory concentrations (MICs) of vancomycin. In addition, these strain pairs were compared for intrinsic virulence and responses to vancomycin therapy in experimental infective endocarditis, a prototypical biofilm model. Results. All sarA mutants displayed significantly reduced biofilm formation and binding to fibronectin but increased protease production in vitro, compared with their respective parental strains. Interestingly, exposure to sub-MICs of vancomycin significantly promoted biofilm formation and fibronectin-binding in parental strains but not in sarA mutants. In addition, all sarA mutants became exquisitely susceptible to vancomycin therapy, compared with their respective parental strains, in the infective endocarditis model. Conclusions. These observations suggest that sarA activation is important in persistent MRSA endovascular infection, potentially in the setting of biofilm formation

Published
2017

62. Deimmunized Lysostaphin Synergizes with Small-Molecule Chemotherapies and Resensitizes Methicillin-Resistant Staphylococcus aureusto β-Lactam Antibiotics

Author

Fang, Yongliang, Kirsch, Jack R., Li, Liang, Brooks, Seth A., Heim, Spencer, Tan, Cynthia, Eszterhas, Susan, Cheng, Hao D., Zhao, Hongliang, Xiong, Yan Q., and Griswold, Karl E.

Abstract

There is an urgent need for novel agents to treat drug-resistant bacterial infections, such as multidrug-resistant Staphylococcus aureus(MRSA). Desirable properties for new antibiotics include high potency, narrow species selectivity, low propensity to elicit new resistance phenotypes, and synergy with standard-of-care (SOC) chemotherapies.

Published
2021
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67. Reduced vancomycin susceptibility in an in vitro catheter-related biofilm model correlates with poor therapeutic outcomes in experimental endocarditis due to methicillin-resistant Staphylococcus aureus

Author

Abdelhady, Wessam, Bayer, Arnold S, Seidl, Kati, Nast, Cynthia C, Kiedrowski, Megan R, Horswill, Alexander R, Yeaman, Michael R, Xiong, Yan Q, University of Zurich, and Xiong, Yan Q

Subjects
10234 Clinic for Infectious Diseases, 3004 Pharmacology, 2736 Pharmacology (medical), 610 Medicine & health, 2725 Infectious Diseases
Published
2013

74. Endovascular Infections Caused by Methicillin-Resistant Staphylococcus aureus Are Linked to Clonal Complex-Specific Alterations in Binding and Invasion Domains of Fibronectin-Binding Protein A as Well as the Occurrence of fnbB

Author

Xiong, Yan Q., primary, Sharma-Kuinkel, Batu K., additional, Casillas-Ituarte, Nadia N., additional, Fowler, Vance G., additional, Rude, Thomas, additional, DiBartola, Alex C., additional, Lins, Roberto D., additional, Abdel-Hady, Wessam, additional, Lower, Steven K., additional, and Bayer, Arnold S., additional

Published
2015
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75. Increased activity of linezolid in combination with rifampicin in a murine pneumonia model due to MRSA.

Author

Yu-Feng Zhou, Xiong, Yan Q., Meng-Ting Tao, Liang Li, Ming-Xiao Bu, Jian Sun, Xiao-Ping Liao, Ya-Hong Liu, Zhou, Yu-Feng, Tao, Meng-Ting, Li, Liang, Bu, Ming-Xiao, Sun, Jian, Liao, Xiao-Ping, and Liu, Ya-Hong

Subjects
*METHICILLIN-resistant staphylococcus aureus, *STAPHYLOCOCCUS aureus, *ANTIBACTERIAL agents, *ANTI-infective agents, *OXAZOLIDINONES, *ANTIBIOTICS, *ANIMAL experimentation, *BACTERIAL proteins, *BIOLOGICAL models, *COMBINATION drug therapy, *COMPARATIVE studies, *DRUG synergism, *RESEARCH methodology, *MEDICAL cooperation, *MICE, *MICROBIAL sensitivity tests, *PNEUMONIA, *RESEARCH, *RIFAMPIN, *STAPHYLOCOCCAL diseases, *EVALUATION research
Abstract

Objectives: The chloramphenicol/florfenicol resistance gene cfr, which mediates cross-resistance to linezolid and other classes of antimicrobial agents, represents a global therapeutic challenge due to its dissemination among MDR nosocomial pathogens, including MRSA. This study aimed to compare the efficacy of the linezolid/rifampicin combination in a murine pneumonia model caused by cfr-positive and cfr-negative clinical MRSA strains.Methods: Synergistic activity between linezolid and rifampicin was evaluated by chequerboard and time-kill assays. Pharmacokinetic profiles in plasma and epithelial lining fluid (ELF) as well as the therapeutic efficacy of linezolid alone and in combination with rifampicin were investigated in a murine pneumonia model. The Emax Hill equation was used to model the dose-response relationship.Results: Increased susceptibility of the study MRSA strains to linezolid was observed with the rifampicin combination (MIC decreased 2- to 16-fold versus linezolid alone). The combination had synergistic activity (fractional inhibitory concentration index ≤0.5) against all cfr-positive MRSA isolates. Linezolid demonstrated excellent pulmonary penetration with an ELF/fplasma AUC ratio of 2.68 ± 0.17. The addition of rifampicin significantly improved the efficacy of linezolid in the pneumonia model due to cfr-positive and cfr-negative MRSA strains. The fAUC/MIC targets of linezolid associated with stasis, 1 log10 kill and 2 log10 kill were 15.9, 38.8 and 175 in plasma, and 43.5, 108 and 415 in ELF, respectively. Importantly, the linezolid fAUC/MIC targets in both plasma and ELF were 2.4-6.7 times lower in combined linezolid/rifampicin therapy versus linezolid monotherapy (P < 0.005).Conclusions: Combination of linezolid with rifampicin significantly improved the efficacy of linezolid in the murine pneumonia model caused by MRSA strains in the presence and absence of the cfr gene. [ABSTRACT FROM AUTHOR]

Published
2018
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76. Experimental Endocarditis Model of Methicillin Resistant Staphylococcus aureus (MRSA) in Rat

Author

Hady, Wessam Abdel, Bayer, Arnold S., and Xiong, Yan Q.

Subjects
Methicillin-Resistant Staphylococcus aureus, Rats, Sprague-Dawley, Disease Models, Animal, Sheep, Virulence, Animals, Female, Endocarditis, Bacterial, Staphylococcal Infections, Infection, Rats
Abstract

Endovascular infections, including endocarditis, are life-threatening infectious syndromes1-3. Staphylococcus aureus is the most common world-wide cause of such syndromes with unacceptably high morbidity and mortality even with appropriate antimicrobial agent treatments4-6. The increase in infections due to methicillin-resistant S. aureus (MRSA), the high rates of vancomycin clinical treatment failures and growing problems of linezolid and daptomycin resistance have all further complicated the management of patients with such infections, and led to high healthcare costs7, 8. In addition, it should be emphasized that most recent studies with antibiotic treatment outcomes have been based in clinical settings, and thus might well be influenced by host factors varying from patient-to-patient. Therefore, a relevant animal model of endovascular infection in which host factors are similar from animal-to-animal is more crucial to investigate microbial pathogenesis, as well as the efficacy of novel antimicrobial agents. Endocarditis in rat is a well-established experimental animal model that closely approximates human native valve endocarditis. This model has been used to examine the role of particular staphylococcal virulence factors and the efficacy of antibiotic treatment regimens for staphylococcal endocarditis. In this report, we describe the experimental endocarditis model due to MRSA that could be used to investigate bacterial pathogenesis and response to antibiotic treatment.

Published
2012

77. In vitro Endothelial Cell Damage is Positively Correlated with Enhanced Virulence and Poor Vancomycin Responsiveness in Experimental Endocarditis due to Methicillin Resistant Staphylococcus aureus

Author

Seidl, Kati, Bayer, Arnold S., McKinnell, James A., Ellison, Steven, Filler, Scott G., and Xiong, Yan Q.

Subjects
Methicillin-Resistant Staphylococcus aureus, Endocarditis, Transcription, Genetic, Virulence, Gene Expression Profiling, Endothelial Cells, Vancomycin Resistance, biochemical phenomena, metabolism, and nutrition, Models, Theoretical, Staphylococcal Infections, Article, Anti-Bacterial Agents, Hemolysin Proteins, Vancomycin, Host-Pathogen Interactions, Humans, Peptide Hydrolases
Abstract

The pathogenesis of Staphylococcus aureus infective endocarditis (IE) is postulated to involve invasion and damage of endothelial cells (ECs). However, the precise relationships between S. aureus – EC interactions in vitro and IE virulence and treatment outcomes in vivo are poorly defined. Ten methicillin-resistant S. aureus (MRSA) clinical isolates previously tested for their virulence and vancomycin responsiveness in an experimental IE model were assessed in vitro for their hemolytic activity, protease production, and capacity to invade and damage ECs. There was a significant positive correlation between the in vitro EC damage caused by these MRSA strains and their virulence during experimental IE (in terms of bacterial densities in target tissues; P < 0.02). Importantly, higher EC damage was also significantly correlated with poor microbiologic response to vancomycin in the IE model (P < 0.001). Interestingly, the extent of EC damage was unrelated to a strain's ability to invade ECs, hemolytic activity and protease production, or β-toxin gene transcription. Inactivation of the agr locus in two MRSA strains caused ∼20% less damage as compared to the corresponding parental strains, indicating that a functional agr is required for maximal EC damage induction. Thus, MRSA-induced EC damage in vitro is a unique virulence phenotype that is independent of many other prototypical MRSA virulence factors, and may be a key biomarker for predicting MRSA virulence potential and antibiotic outcomes during endovascular infections.

Published
2011

80. Synergistic Effect of Pleuromutilins with Other Antimicrobial Agents against Staphylococcus aureus In Vitro and in an Experimental Galleria mellonella Model.

Author

Chun-Liu Dong, Lin-Xiong Li, Ze-Hua Cui, Shu-Wen Chen, Xiong, Yan Q., Jia-Qi Lu, Xiao-Ping Liao, Yuan Gao, Jian Sun, and Ya-Hong Liu

Subjects
GREATER wax moth, ANTI-infective agents, METHICILLIN-resistant staphylococcus aureus
Abstract

Invasive infections due to Staphylococcus aureus, including methicillin-resistant S. aureus are prevalent and life-threatening. Combinations of antibiotic therapy have been employed in many clinical settings for improving therapeutic efficacy, reducing side effects of drugs, and development of antibiotic resistance. Pleuromutilins have a potential to be developed as a new class of antibiotics for systemic use in humans. In the current study, we investigated the relationship between pleuromutilins, including valnemulin, tiamulin, and retapamulin, and 13 other antibiotics representing different mechanisms of action, against methicillin-susceptible and -resistant S. aureus both in vitro and in an experimental Galleria mellonella model. In vitro synergistic effects were observed in combination of all three study pleuromutilins with tetracycline (TET) by standard checkerboard and/or time-kill assays. In addition, the combination of pleuromutilins with ciprofloxacin or enrofloxacin showed antagonistic effects, while the rest combinations presented indifferent effects. Importantly, all study pleuromutilins in combination with TET significantly enhanced survival rates as compared to the single drug treatment in the G. mellonella model caused by S. aureus strains. Taken together, these results demonstrated synergy effects between pleuromutilins and TET against S. aureus both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Published
2017
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84. Reduced Vancomycin Susceptibility in an In Vitro Catheter-Related Biofilm Model Correlates with Poor Therapeutic Outcomes in Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus

Author

Abdelhady, Wessam, primary, Bayer, Arnold S., additional, Seidl, Kati, additional, Nast, Cynthia C., additional, Kiedrowski, Megan R., additional, Horswill, Alexander R., additional, Yeaman, Michael R., additional, and Xiong, Yan Q., additional

Published
2013
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85. Pharmacokinetic/Pharmacodynamic Correlation of Cefquinome Against Experimental Catheter-Associated Biofilm Infection Due to Staphylococcus aureus.

Author

Yu-Feng Zhou, Wei Shi, Yang Yu, Meng-Ting Tao, Xiong, Yan Q., Jian Sun, Ya-Hong Liu, Gnanamani, A., and Ip, Margaret

Subjects
STAPHYLOCOCCUS aureus, BIOFILMS, ANTIBIOTICS
Abstract

Biofilm formations play an important role in Staphylococcus aureus pathogenesis and contribute to antibiotic treatment failures in biofilm-associated infections. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of cefquinome against an experimental catheter-related biofilm model due to S. aureus, including three clinical isolates and one non-clinical isolate. The minimal inhibitory concentration (MIC), minimal biofilm inhibitory concentration (MBIC), biofilm bactericidal concentration (BBC), minimal biofilm eradication concentration (MBEC) and biofilm prevention concentration (BPC) and in vitro time-kill curves of cefquinome were studied in both planktonic and biofilm cells of study S. aureus strains. The in vivo postantibiotic effects (PAEs), PK profiles and efficacy of cefquinome were performed in the catheter-related biofilm infection model in murine. A sigmoid Emax model was utilized to determine the PK/PD index that best described the dose-response profiles in the model. The MICs and MBICs of cefquinome for the four S. aureus strains were 0.5 and 16 µg/mL, respectively. The BBCs (32-64 µg/mL) and MBECs (64- 256 µg/mL) of these study strains were much higher than their corresponding BPC values (1-2 μg/mL). Cefquinome showed time-dependent killing both on planktonic and biofilm cells, but produced much shorter PAEs in biofilm infections. The bestcorrelated PK/PD parameters of cefquinome for planktonic and biofilm cells were the duration of time that the free drug level exceeded the MIC (fT > MIC, R² = 96.2%) and the MBIC (fT > MBIC, R² = 94.7%), respectively. In addition, the AUC24h/MBIC of cefquinome also significantly correlated with the anti-biofilm outcome in this model (R² = 93.1%). The values of AUC24h/MBIC for biofilm-static and 1-log10-unit biofilmcidal activity were 22.8 and 35.6 h; respectively. These results indicate that the PK/PD profiles of cefquinome could be used as valuable guidance for effective dosing regimens treating S. aureus biofilm-related infections. [ABSTRACT FROM AUTHOR]

Published
2016
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86. Correction: A Structural Model for Binding of the Serine-Rich Repeat Adhesin GspB to Host Carbohydrate Receptors

Author

Pyburn, Tasia M., primary, Bensing, Barbara A., additional, Xiong, Yan Q., additional, Melancon, Bruce J., additional, Tomasiak, Thomas M., additional, Ward, Nicholas J., additional, Yankovskaya, Victoria, additional, Oliver, Kevin M., additional, Cecchini, Gary, additional, Sulikowski, Gary A., additional, Tyska, Matthew J., additional, Sullam, Paul M., additional, and Iverson, T. M., additional

Published
2012
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93. A Structural Model for Binding of the Serine-Rich Repeat Adhesin GspB to Host Carbohydrate Receptors

Author

Pyburn, Tasia M., primary, Bensing, Barbara A., additional, Xiong, Yan Q., additional, Melancon, Bruce J., additional, Tomasiak, Thomas M., additional, Ward, Nicholas J., additional, Yankovskaya, Victoria, additional, Oliver, Kevin M., additional, Cecchini, Gary, additional, Sulikowski, Gary A., additional, Tyska, Matthew J., additional, Sullam, Paul M., additional, and Iverson, T. M., additional

Published
2011
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