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19. Successive influenza virus infection and Streptococcus pneumoniae stimulation alter human dendritic cell function

Author

Tu Wenwei, Ho Pak-Leung, Chow Kin-Hung, Ling Man-To, Mao Huawei, Wu Yuet, and Lau Yu-Lung

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Influenza virus is a major cause of respiratory disease worldwide and Streptococcus pneumoniae infection associated with influenza often leads to severe complications. Dendritic cells are key antigen presenting cells but its role in such co-infection is unclear. Methods In this study, human monocyte derived-dentritic cells were either concurrently or successively challenged with the combination of live influenza virus and heat killed pneumococcus to mimic the viral pneumococcal infection. Dendritic cell viability, phenotypic maturation and cytokine production were then examined. Results The challenge of influenza virus and pneumococcus altered dendritic cell functions dependent on the time interval between the successive challenge of influenza virus and pneumococcus, as well as the doses of pneumococcus. When dendritic cells were exposed to pneumococcus at 6 hr, but not 0 hr nor 24 hr after influenza virus infection, both virus and pneumococcus treated dendritic cells had greater cell apoptosis and expressed higher CD83 and CD86 than dendritic cells infected with influenza virus alone. Dendritic cells produced pro-inflammatory cytokines: TNF-α, IL-12 and IFN-γ synergistically to the successive viral and pneumococcal challenge. Whereas prior influenza virus infection suppressed the IL-10 response independent of the timing of the subsequent pneumococcal stimulation. Conclusions Our results demonstrated that successive challenge of dendritic cells with influenza virus and pneumococcus resulted in synergistic up-regulation of pro-inflammatory cytokines with simultaneous down-regulation of anti-inflammatory cytokine, which may explain the immuno-pathogenesis of this important co-infection.

Published
2011
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23. Evaluation of disc diffusion tests and agar screening for predicting mecA-mediated oxacillin resistance in Staphylococcus lugdunensisrevealed a cefoxitin-susceptible, mecA-positive S. lugdunensisclonal complex 27 clone

Author

Ho, Pak-Leung, Liu, Melissa Chun-Jiao, Tong, Man-Ki, Fan, Pui-Man, Tse, Cindy Wing-Sze, Wu, Alan Ka-Lun, Cheng, Vincent Chi-Chung, and Chow, Kin-Hung

Abstract

•Oxacillin (mecA) resistance in Staphylococcus lugdunensisis emerging.•Phenotypic methods were evaluated for predicting mecAin S. lugdunensis.•Cefoxitin disc testing using current CLSI 2019 breakpoints was unreliable.•Strains of S. lugdunensisCC27/SCCmecV clone were cefoxitin-susceptible (i.e. MIC ≤ 4 μg/mL).•Oxacillin agar screening can detect all mecA-positive isolates.

Published
2020
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28. Occurrence of Highly Conjugative IncX3 Epidemic Plasmid Carrying bla NDM in Enterobacteriaceae Isolates in Geographically Widespread Areas.

Author

Wang, Ya, Tong, Man-Ki, Chow, Kin-Hung, Cheng, Vincent Chi-Chung, Tse, Cindy Wing-Sze, Wu, Alan Ka-Lun, Lai, Raymond Wai-Man, Luk, Wei-Kwang, Tsang, Dominic Ngai-Chong, and Ho, Pak-Leung

Subjects
ENTEROBACTERIACEAE, BACTERIAL conjugation, PLASMIDS
Abstract

The emergence of New Delhi metallo-β-lactamase (NDM) in common enterobacterial species is a major concern for healthcare. Early reports have revealed that the spread of NDM involved diverse and heterogeneous plasmids. Recently, the involvement of a rare, IncX3 subtype plasmid has been increasingly recognized. Here, we studied the prevalence of IncX plasmid subtypes in 198 carbapenem-resistant Enterobacteriaceae , originating from a territory-wide active surveillance in Hong Kong in 2016. The complete sequences and biological features of the bla NDM-carrying plasmids were investigated. A total of 62 NDM-type, 21 OXA-48 type, 14 IMP-type, 8 KPC-type, 4 IMI-type producers, and 89 non-carbapenemase-producers were tested for presence of IncX subtypes. IncX3 (n = 60) was the most common subtype, followed by IncX4 (n = 6) and IncX1 (n = 2). The prevalence of IncX3 subtype in isolates producing NDM, other carbapenemase types and non-carbapenemase producers were 75.8, 21.3, and 3.4%, respectively (P < 0.001). An IncX3 plasmid (size ∼50 kb) was confirmed to carry bla NDM in 47 isolates of different enterobacterial species. Thirteen IncX3 plasmids originating from six healthcare regions in Hong Kong were completely sequenced. The results showed that the IncX3 plasmids carrying bla NDM share a high degree of sequence identity with a previously reported plasmid, pNDM-HN380 (GenBank accession JX104760), over the backbone and genetic load regions. A blast search further revealed the occurrence of identical or nearly identical IncX3 plasmids carrying bla NDM in other part of China, Korea, Myanmar, India, Oman, Kuwait, Italy, and Canada. Two IncX3 carrying bla NDM were investigated further. Conjugation experiments demonstrated that the IncX3 plasmids could be efficiently transferred to multiple enterobacterial species at frequencies that are comparable or higher than the epidemic IncFII plasmid carrying bla CTX-M (pHK01). In addition, efficient transfer of the NDM plasmids occurred over a range of temperatures. In conclusion, this study demonstrated the important role played by IncX3 in the dissemination of NDM and the occurrence of pNDM-HN380-like plasmids in geographically widespread areas. The high mobility of IncX3 plasmid across different enterobacterial species highlights the ability of this plasmid replicon to be an important vehicle in worldwide dissemination of NDM. [ABSTRACT FROM AUTHOR]

Published
2018
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30. Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

Author

Wu, Yuet, primary, Tu, Wenwei, additional, Lam, Kwok-Tai, additional, Chow, Kin-Hung, additional, Ho, Pak-Leung, additional, Guan, Yi, additional, Peiris, Joseph S. Malik, additional, and Lau, Yu-Lung, additional

Published
2015
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37. Using beta-lactamase to trigger supramolecular hydrogelation

Author

Yang, Zhimou, Ho, Pak-Leung, Liang, Gaolin, Chow, Kin Hung, Wang, Qigang, Cao, Yang, Guo, Zhihong, Xu, Bing, Yang, Zhimou, Ho, Pak-Leung, Liang, Gaolin, Chow, Kin Hung, Wang, Qigang, Cao, Yang, Guo, Zhihong, and Xu, Bing

Abstract

This paper reports the rational design and synthesis of a beta-lactam conjugate. Treating the conjugate with beta-lactamase cleaves the scissile -lactam amide bond, releases a hydrogelator, and results in enzymatic formation of a supramolecular hydrogel. The process involves the use of a bacterial enzyme-the one causes antibiotic inactivation and accounts for resistance to beta-lactams in many clinical important pathogens-to catalyze the formation of the hydrogel. It offers an opportunity to investigate the kinetics of these types of enzymatic reactions, screen inhibitors of the enzyme, and provides a new candidate to generate hydrogels for biomedical applications.

Published
2007

39. Identification and characterization of a novel incompatibility group X3 plasmid carrying blaNDM-1 in Enterobacteriaceae isolates with epidemiological links to multiple geographical areas in China

Author

Ho, Pak-Leung, primary, Li, Zhen, additional, Lo, Wai-U, additional, Cheung, Yuk-Yam, additional, Lin, Chi-Ho, additional, Sham, Pak-Chung, additional, Chi-Chung Cheng, Vincent, additional, Ng, Tak-Keung, additional, Que, Tak-Lun, additional, and Chow, Kin-Hung, additional

Published
2012
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40. A Novel Selective Medium for Isolation of Bacteroides fragilisfrom Clinical Specimens

Author

Ho, Pak-Leung, Ho, Lok-Yan, Yau, Chong-Yee, Tong, Man-Ki, and Chow, Kin-Hung

Abstract

ABSTRACTA novel Bacteroides fragilisselective (BFS) medium, consisting of a brain heart infusion agar base supplemented with yeast extract, cysteine hydrochloride, bile salts, vitamin K, hemin, glucose, esculin, ferric ammonium citrate, bromothymol blue, gentamicin, kanamycin, and novobiocin, was evaluated. When BFS agar was tested with a collection of 303 bacteria of different genera, it allowed the growth of B. fragilisas large yellow colonies, with blackening of the medium after 48 h of anaerobic incubation, while the growth of most other anaerobes, facultative anaerobes, and aerobes was inhibited. In a prospective comparison of BFS agar with a routinely used medium (neomycin blood agar) in 1,209 clinical specimens, 60 B. fragilisbacteria were detected on BFS agar while 46 were detected on the routine agar (McNemar's test, P= 0.008). In conclusion, this novel medium may be added to improve the recovery of B. fragilisin clinical specimens and to facilitate surveillance of antimicrobial-resistant strains.

Published
2016
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45. Plasmid-Mediated OqxAB Is an Important Mechanism for Nitrofurantoin Resistance in Escherichia coli

Author

Ho, Pak-Leung, Ng, Ka-Ying, Lo, Wai-U, Law, Pierra Y., Lai, Eileen Ling-Yi, Wang, Ya, and Chow, Kin-Hung

Abstract

ABSTRACTIncreasing consumption of nitrofurantoin (NIT) for treatment of acute uncomplicated urinary tract infections (UTI) highlights the need to monitor emerging NIT resistance mechanisms. This study investigated the molecular epidemiology of the multidrug-resistant efflux gene oqxABand its contribution to nitrofurantoin resistance by using Escherichia coliisolates originating from patients with UTI (n= 205; collected in 2004 to 2013) and food-producing animals (n= 136; collected in 2012 to 2013) in Hong Kong. The oqxABgene was highly prevalent among NIT-intermediate (11.5% to 45.5%) and -resistant (39.2% to 65.5%) isolates but rare (0% to 1.7%) among NIT-susceptible (NIT-S) isolates. In our isolates, the oqxABgene was associated with IS26and was carried by plasmids of diverse replicon types. Multilocus sequence typing revealed that the clones of oqxAB-positive E. coliwere diverse. The combination of oqxABand nfsAmutations was found to be sufficient for high-level NIT resistance. Curing of oqxAB-carrying plasmids from 20 NIT-intermediate/resistant UTI isolates markedly reduced the geometric mean MIC of NIT from 168.9 μg/ml to 34.3 μg/ml. In the plasmid-cured variants, 20% (1/5) of isolates with nfsAmutations were NIT-S, while 80% (12/15) of isolates without nfsAmutations were NIT-S (P= 0.015). The presence of plasmid-based oqxABincreased the mutation prevention concentration of NIT from 128 μg/ml to 256 μg/ml and facilitated the development of clinically important levels of nitrofurantoin resistance. In conclusion, plasmid-mediated oqxABis an important nitrofurantoin resistance mechanism. There is a great need to monitor the dissemination of this transferable multidrug-resistant efflux pump.

Published
2015
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46. Novel Selective Medium for Isolation of Staphylococcus lugdunensisfrom Wound Specimens

Author

Ho, Pak-Leung, Leung, Sammy Man-Him, Tse, Herman, Chow, Kin-Hung, Cheng, Vincent Chi-Chung, and Que, Tak-Lun

Abstract

ABSTRACTWe compared a novel selective Staphylococcus lugdunensis(SSL) medium with routine media (blood and chocolate agars) for the detection of S. lugdunensisin 990 clinical specimens (from tissue, pus, or wound swabs). Significantly more S. lugdunensisisolates were detected on SSL medium (34/990) than on routine medium (7/990) (P= 0.001, McNemar's test).

Published
2014
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48. Emergence of Fluoroquinolone Resistance among Multiply Resistant Strains of Streptococcus pneumoniaein Hong Kong

Author

Ho, Pak-Leung, Que, Tak-Lun, Tsang, Dominic Ngai-Chong, Ng, Tak-Keung, Chow, Kin-Hung, and Seto, Wing-Hon

Abstract

ABSTRACTThe MICs of 17 antimicrobial agents for 181 Streptococcus pneumoniaestrains were determined by the E-test. Overall, 69.1% were penicillin resistant (MIC > 0.06 μg/ml). Resistance to ciprofloxacin (MIC > 2 μg/ml), levofloxacin (MIC > 2 μg/ml), or trovafloxacin (MIC > 1 μg/ml) was found in 12.1, 5.5, or 2.2% of the strains, respectively. These high rates of resistance raise concerns for the future.

Published
1999
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49. Clonality and Antimicrobial Susceptibility of Staphylococcus aureusand Methicillin-Resistant S. aureusIsolates from Food Animals and Other Animals

Author

Ho, Pak-Leung, Chow, Kin-Hung, Lai, Eileen L., Law, Pierra Y. T., Chan, Pui-Ying, Ho, Alex Y. M., Ng, Tak-Keung, and Yam, Wing-Cheong

Abstract

ABSTRACTOut of 3,081 animals studied, 24.9% of pigs, 4.7% of chickens, 6.3% of dogs, 10.5% of cats, and 7.1% of rodents were Staphylococcus aureuspositive. Prevalence of methicillin-resistant S. aureus(MRSA) was high in pigs (animals, 21.3%; batches, 46.5%), with all MRSA isolates and most methicillin-sensitive S. aureusisolates belonging to clonal complex 9 (CC9) and being multidrug resistant. The predominant S. aureusCCs among dog and cat isolates were similar. Among rodent isolates, CC398 predominated, with spat034 the most frequent spatype detected.

Published
2012
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50. IncX3 Epidemic Plasmid Carrying blaNDM-5in Escherichia colifrom Swine in Multiple Geographic Areas in China

Author

Ho, Pak-Leung, Wang, Ya, Liu, Melissa Chun-Jiao, Lai, Eileen Ling-Yi, Law, Pierra Ying-Tung, Cao, Huiluo, and Chow, Kin-Hung

Abstract

ABSTRACTSix imported pigs originating from Guangdong, Henan, and Hunan provinces in China during October 2015 to February 2017 were cultured and found to be positive for meropenem-resistant Escherichia coli. The samples yielded 9 E. coliisolates of diverse sequence types carrying blaNDM-5on IncX3 (8 isolates from 5 farms) or IncFII (1 isolate from 1 farm) plasmids. The mcr-1gene was coharbored by 4 isolates. The IncX3 plasmids (∼46 kb) carrying blaNDM-5were identical or nearly identical to each other.

Published
2018
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