Publications by authors named "Marcus Ho Yin Wong"

26 Publications

  • Page 1 of 1

Structural and Functional Characterization of OXA-48: Insight into Mechanism and Structural Basis of Substrate Recognition and Specificity.

Int J Mol Sci 2021 Oct 25;22(21). Epub 2021 Oct 25.

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong, China.

Class D β-lactamase OXA-48 is widely distributed among Gram-negative bacteria and is an important determinant of resistance to the last-resort carbapenems. Nevertheless, the detailed mechanism by which this β-lactamase hydrolyzes its substrates remains poorly understood. In this study, the complex structures of OXA-48 and various β-lactams were modeled and the potential active site residues that may interact with various β-lactams were identified and characterized to elucidate their roles in OXA-48 substrate recognition. Four residues, namely S, K, S, and K were found to be essential for OXA-48 to undergo catalytic hydrolysis of various penicillins and carbapenems both in vivo and in vitro. T was found to be important for hydrolysis of imipenem, whereas R played a major role in hydrolyzing ampicillin, imipenem, and meropenem most likely by forming a H-bond or salt-bridge between the side chain of these two residues and the carboxylate oxygen ions of the substrates. Analysis of the effect of substitution of alanine in two residues, W and L, revealed their roles in mediating the activity of OXA-48. Our data show that these residues most likely undergo hydrophobic interaction with the R groups and the core structure of the β-lactam ring in penicillins and the carbapenems, respectively. Unlike OXA-58, mass spectrometry suggested a loss of the C6-hydroxyethyl group during hydrolysis of meropenem by OXA-48, which has never been demonstrated in Class D carbapenemases. Findings in this study provide comprehensive knowledge of the mechanism of the substrate recognition and catalysis of OXA-type β-lactamases.
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http://dx.doi.org/10.3390/ijms222111480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583920PMC
October 2021

Active maintenance of proton motive force mediates starvation-induced bacterial antibiotic tolerance in Escherichia coli.

Commun Biol 2021 09 14;4(1):1068. Epub 2021 Sep 14.

Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.

Recent evidence suggests that metabolic shutdown alone does not fully explain how bacteria exhibit phenotypic antibiotic tolerance. In an attempt to investigate the range of starvation-induced physiological responses underlying tolerance development, we found that active maintenance of the transmembrane proton motive force (PMF) is essential for prolonged expression of antibiotic tolerance in bacteria. Eradication of tolerant sub-population could be achieved by disruption of PMF using the ionophore CCCP, or through suppression of PMF maintenance mechanisms by simultaneous inhibition of the phage shock protein (Psp) response and electron transport chain (ETC) complex activities. We consider disruption of bacterial PMF a feasible strategy for treatment of chronic and recurrent bacterial infections.
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http://dx.doi.org/10.1038/s42003-021-02612-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440630PMC
September 2021

Over-Expression of IS-Linked Intrinsic and Exogenously Acquired OXA Type Carbapenem-Hydrolyzing-Class D-ß-Lactamase-Encoding Genes Is Key Mechanism Underlying Carbapenem Resistance in .

Front Microbiol 2019 4;10:2809. Epub 2019 Dec 4.

State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Kowloon, Hong Kong.

is an important clinical pathogen which often causes fatal infections among seriously ill patients. Treatment options for managing infections caused by this organism have become limited as a result of emergence of carbapenem resistant strains. In the current study, whole genome sequencing, gene expression studies and enzyme kinetics analyses were performed to investigate the underlying carbapenem resistance mechanisms in fourteen clinical strains isolated from two hospitals, one each in Hong Kong and Henan Province, People's Republic of China. A large majority of the strains (11/14) were found to belong to the International Clone II (IC-II), among which six were ST208. Twelve of these strains were carbapenem resistant and found to either harbor / , or exhibit over-expression of the gene upon IS insertion. Enzymatic assay confirmed that the OXA variants, including those of , exhibited strong carbapenem-degrading activities. In terms of other intrinsic mechanisms, a weak correlation was observed between reduced production of outer membrane porin CarO/expression resistance-nodulation-division (RND) efflux AdeB and phenotypic resistance. This finding implied that over-production of carbapenem-hydrolyzing-class D-ß-lactamases (CHDLs), including the intrinsic gene and the acquired and elements, is the key mechanism of carbapenem resistance in . This view is confirmed by testing the effect of NaCl, a known inhibitor, which was found to cause reduction in carbapenem MIC by twofolds to eightfolds, suggesting that inhibiting OXA type carbapenemases represents the most effective strategy to control phenotypic carbapenem resistance in .
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http://dx.doi.org/10.3389/fmicb.2019.02809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904305PMC
December 2019

Erratum to: Efficient generation of complete sequences of MDR-encoding plasmids by rapid assembly of MinION barcoding sequencing data.

Gigascience 2019 03;8(3)

Shenzhen Key Lab for Food Biological Safety Control, Food Safety and Technology Research Center, Hong Kong PolyU Shen Zhen Research Institute, Shenzhen, P. R. China.

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http://dx.doi.org/10.1093/gigascience/giz031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443574PMC
March 2019

First detection of a bla-carrying plasmid in Vibrio alginolyticus.

J Glob Antimicrob Resist 2018 06 19;13:206-208. Epub 2018 Apr 19.

Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, The Hong Kong PolyU Shenzhen Research Institute, Shenzhen, Guangdong Province, PR China; State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. Electronic address:

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http://dx.doi.org/10.1016/j.jgar.2018.04.007DOI Listing
June 2018

Efficient generation of complete sequences of MDR-encoding plasmids by rapid assembly of MinION barcoding sequencing data.

Gigascience 2018 03;7(3):1-9

Shenzhen Key Lab for Food Biological Safety Control, Food Safety and Technology Research Center, Hong Kong PolyU Shen Zhen Research Institute, Shenzhen, P. R. China.

Background: Multidrug resistance (MDR)-encoding plasmids are considered major molecular vehicles responsible for transmission of antibiotic resistance genes among bacteria of the same or different species. Delineating the complete sequences of such plasmids could provide valuable insight into the evolution and transmission mechanisms underlying bacterial antibiotic resistance development. However, due to the presence of multiple repeats of mobile elements, complete sequencing of MDR plasmids remains technically complicated, expensive, and time-consuming.

Results: Here, we demonstrate a rapid and efficient approach to obtaining multiple MDR plasmid sequences through the use of the MinION nanopore sequencing platform, which is incorporated in a portable device. By assembling the long sequencing reads generated by a single MinION run according to a rapid barcoding sequencing protocol, we obtained the complete sequences of 20 plasmids harbored by multiple bacterial strains. Importantly, single long reads covering a plasmid end-to-end were recorded, indicating that de novo assembly may be unnecessary if the single reads exhibit high accuracy.

Conclusions: This workflow represents a convenient and cost-effective approach for systematic assessment of MDR plasmids responsible for treatment failure of bacterial infections, offering the opportunity to perform detailed molecular epidemiological studies to probe the evolutionary and transmission mechanisms of MDR-encoding elements.
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http://dx.doi.org/10.1093/gigascience/gix132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848804PMC
March 2018

Emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae.

Lancet Infect Dis 2018 01 1;18(1):24. Epub 2017 Nov 1.

Shenzhen Key lab for Food Biological Safety Control, Food Safety and Technology Research Center, Hong Kong PolyU Shen Zhen Research Institute, Shenzhen, China; State Key Lab of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China. Electronic address:

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http://dx.doi.org/10.1016/S1473-3099(17)30629-1DOI Listing
January 2018

IS26-mediated formation of a virulence and resistance plasmid in Salmonella Enteritidis.

J Antimicrob Chemother 2017 10;72(10):2750-2754

Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, The Hong Kong PolyU Shenzhen Research Institute, Shenzhen, P. R. China.

Objectives: To characterize a novel virulence-resistance plasmid pSE380T carried by a Salmonella enterica serotype Enteritidis clinical strain SE380.

Methods: The plasmid pSE380T was conjugated to Escherichia coli strain J53 and sequenced by PacBio RSII, followed by subsequent annotation and genetic analysis.

Results: Sequence analysis of this plasmid revealed that the entire Salmonella Enteritidis-specific virulence plasmid, pSEN, had been incorporated into an IncHI2 MDR plasmid, which comprises the cephalosporin and fosfomycin resistance determinants blaCTX-M-14 and fosA3. Based on BLAST analysis and scrutiny of insertion footprints, the insertion event was found to involve a replicative transposition process mediated by IS26, an IS element frequently detected in various resistance plasmids. The resulting pSE380T plasmid also comprises backbone elements of IncHI2 and IncFIA plasmids, producing a rare fusion product that simultaneously encodes functional features of both, i.e. virulence, resistance and high transmissibility.

Conclusions: This is a novel hybrid plasmid mediating MDR and virulence from a clinical Salmonella Enteritidis strain. This plasmid is likely to be transmissible amongst various serotypes of Salmonella and other Enterobacteriaceae species, rendering a wide range of bacterial pathogens resistant to cephalosporins and fosfomycin, and further enhancing their virulence potential. It will be important to monitor the spread and further evolution of this plasmid among the Enterobacteriaceae strains.
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http://dx.doi.org/10.1093/jac/dkx238DOI Listing
October 2017

Evolution and comparative genomics of pAQU-like conjugative plasmids in Vibrio species.

J Antimicrob Chemother 2017 09;72(9):2503-2506

Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, The Hong Kong PolyU Shenzhen Research Institute, Shenzhen, P. R. China.

Objectives: To investigate a set of MDR conjugative plasmids found in Vibrio species and characterize the underlying evolution process.

Methods: pAQU-type plasmids from Vibrio species were sequenced using both Illumina and PacBio platforms. Bioinformatics tools were utilized to analyse the typical MDR regions and core genes in the plasmids.

Results: The nine pAQU-type plasmids ranged from ∼160 to 206 kb in size and were found to harbour as many as 111 core genes encoding conjugative, replication and maintenance functions. Eight plasmids were found to carry a typical MDR region, which contained various accessory and resistance genes, including ISCR1-blaPER-1-bearing complex class 1 integrons, ISCR2-floR, ISCR2-tet(D)-tetR-ISCR2, qnrVC6, a Tn10-like structure and others associated with mobile elements. Comparison between a plasmid without resistance genes and different MDR plasmids showed that integration of different mobile elements, such as IS26, ISCR1, ISCR2, IS10 and IS6100, into the plasmid backbone was the key mechanism by which foreign resistance genes were acquired during the evolution process.

Conclusions: This study identified pAQU-type plasmids as emerging MDR conjugative plasmids among important pathogens from different origins in Asia. These findings suggest that aquatic bacteria constitute a major reservoir of resistance genes, which may be transmissible to other human pathogens during food production and processing.
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http://dx.doi.org/10.1093/jac/dkx193DOI Listing
September 2017

IncHI2 Plasmids Are the Key Vectors Responsible for oqxAB Transmission among Salmonella Species.

Antimicrob Agents Chemother 2016 11 21;60(11):6911-6915. Epub 2016 Oct 21.

Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, The Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China

This study reported and analyzed the complete sequences of two oqxAB-bearing IncHI2 plasmids harbored by a clinical Salmonella enterica serovar Typhimurium strain and an S Indiana strain of animal origin, respectively. In particular, pA3T recovered from S Indiana comprised the resistance determinants oqxAB, aac(6')Ib-cr, fosA3, and bla Further genetic screening of 63 oqxAB-positive Salmonella isolates revealed that the majority carried IncHI2 plasmids, confirming that such plasmids play a pivotal role in dissemination of oqxAB in Salmonella spp.
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http://dx.doi.org/10.1128/AAC.01555-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075106PMC
November 2016

IncI1 Plasmids Carrying Various blaCTX-M Genes Contribute to Ceftriaxone Resistance in Salmonella enterica Serovar Enteritidis in China.

Antimicrob Agents Chemother 2016 Feb 7;60(2):982-9. Epub 2015 Dec 7.

State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, The Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China

Resistance to extended-spectrum β-lactams in Salmonella, in particular, in serotypes such as Salmonella enterica serovar Enteritidis that are frequently associated with clinical infections, is a serious public health concern. In this study, phenotypic characterization of 433 clinical S. Enteritidis strains obtained from a nationwide collection of the Chinese Center for Disease Control and Prevention during the period from 2005 to 2010 depicted a trend of increasing resistance to ceftriaxone from 2008 onwards. Seventeen (4%) of the strains were found to be resistant to ceftriaxone, 7% were found to be resistant to ciprofloxacin, and 0.7% were found to be resistant to both ciprofloxacin and ceftriaxone. Most of the ceftriaxone-resistant S. Enteritidis strains (15/17) were genetically unrelated and originated from Henan Province. The complete sequence of an IncI1 plasmid, pSE115, which belonged to a novel sequence type, was obtained. This 87,255-bp IncI1 plasmid was found to harbor a blaCTX-M-14 gene in a novel multidrug resistance region (MRR) within the tra locus. Although the majority of strains were also found to contain conjugative IncI1 plasmids with a size similar to that of pSE115 (∼90 kb) and harbor a variety of blaCTX-M group 1 and group 9 elements, the novel MRR site at the tra locus in pSE115 was not detectable in the other IncI1 plasmids. The findings from this study show that cephalosporin resistance in S. Enteritidis strains collected in China was mainly due to the dissemination of IncI1 plasmids carrying blaCTX-M, resembling the situation in which IncI1 plasmids serve as major vectors of blaCTX-M variants in other members of the Enterobacteriaceae.
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http://dx.doi.org/10.1128/AAC.02746-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4750657PMC
February 2016

Isolation of carbapenem-resistant Pseudomonas spp. from food.

J Glob Antimicrob Resist 2015 Jun 27;3(2):109-114. Epub 2015 Apr 27.

Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, PR China; State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. Electronic address:

Pseudomonas spp. are ubiquitous in nature. Carbapenem resistance in environmental isolates of members of this genus is thought to be rare but the exact resistance rate is unknown. In this study, carbapenem-resistant Pseudomonas spp. were isolated from chicken and pork samples and the mechanisms underlying the carbapenem resistance in these strains were investigated. A total of 16 carbapenem-resistant Pseudomonas aeruginosa, Pseudomonas putida and Pseudomonas otitidis isolates were recovered from eight samples of chicken and pork. The isolates exhibited meropenem minimum inhibitory concentrations (MICs) of 8 to ≥32mg/L and imipenem MICs of <0.5-16mg/L yet did not harbour any acquired carbapenemase genes. Meropenem resistance in various strains was found to be mediated by efflux systems only, whereas overexpression of MexAB-OprM efflux pump and lack of OprD porin were responsible for carbapenem resistance in P. aeruginosa. The intrinsic metallo-β-lactamase gene bla in P. otitidis and overexpression of the TtgABC efflux system in P. putida were also responsible for carbapenem resistance in these organisms. In conclusion, this study reports for the first time the isolation of carbapenem-resistant P. aeruginosa, P. otitidis and P. putida strains from food. The resistance mechanisms of these strains are rarely due to production of carbapenemases. Further selection of such carbapenem-resistant Pseudomonas spp. in the environment and the risk by which they are transmitted to clinical settings are of great public health concern.
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http://dx.doi.org/10.1016/j.jgar.2015.03.006DOI Listing
June 2015

Dissemination of IncI2 Plasmids That Harbor the blaCTX-M Element among Clinical Salmonella Isolates.

Antimicrob Agents Chemother 2015 Aug 26;59(8):5026-8. Epub 2015 May 26.

Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, The Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong

The extended-spectrum-β-lactamase (ESBL) determinant CTX-M-55 is increasingly prevalent in Escherichia coli but remains extremely rare in Salmonella. This study reports the isolation of a plasmid harboring the blaCTX-M-55 element in a clinical Salmonella enterica serotype Typhimurium strain resistant to multiple antibiotics. This plasmid is genetically identical to several known IncI2-type elements harbored by E. coli strains recovered from animals. This finding indicates that IncI2 plasmids harboring the blaCTX-M genes may undergo cross-species migration among potential bacterial pathogens, with E. coli as the major source of such elements.
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http://dx.doi.org/10.1128/AAC.00775-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505288PMC
August 2015

First detection of AmpC β-lactamase bla(CMY-2) on a conjugative IncA/C plasmid in a Vibrio parahaemolyticus isolate of food origin.

Antimicrob Agents Chemother 2015 Jul 27;59(7):4106-11. Epub 2015 Apr 27.

Shenzhen Key Lab for Food Biological Safety Control, Food Safety and Technology Research Center, Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China State Key Lab of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong

Vibrio parahaemolyticus is an important causative agent of gastroenteritis, with the consumption of contaminated seafood being the major transmission route. Resistance to penicillin is common among V. parahaemolyticus strains, whereas cephalosporin resistance remains rare. In an attempt to assess the current prevalence and characteristics of antibiotic resistance of this pathogen in common food samples, a total of 54 (17% of the total samples) V. parahaemolyticus strains were isolated from 318 meat and seafood samples purchased from supermarkets and wet markets in Shenzhen, China, in 2013. These isolates exhibited high-level resistance to ampicillin, yet they were mostly susceptible to other antimicrobials, except for two that were resistant to extended-spectrum cephalosporins. The β-lactamase gene blaPER-1 was detectable in one strain, V. parahaemolyticus V43, which was resistant to both third- and fourth-generation cephalosporins. Compared to other blaPER-1-positive V. parahaemolyticus strains reported in our previous studies, strain V43 was found to harbor an ∼200-kb conjugative plasmid carrying genes that were different from the antimicrobial resistance genes reported from the previous studies. The β-lactamase gene blaCMY-2 was detectable for the first time in another V. parahaemolyticus isolate, V4, which was resistant to third-generation cephalosporins. This blaCMY-2 gene was shown to be located in an ∼150-kb IncA/C-type conjugative plasmid with a genetic structure consisting of traB-traV-traA-ISEcp1-blaCMY-2-blc-sugE-encR-orf1-orf2-orf3-orf4-dsbC-traC, which is identical to that of other IncA/C conjugative plasmids in Enterobacteriaceae, albeit with a different size. These findings indicate that the transmission of extended-spectrum-β-lactamase (ESBL) and AmpC β-lactamase genes via conjugative plasmids can mediate the development of extended-spectrum cephalosporin resistance in V. parahaemolyticus, thereby posing a potential threat to public health.
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http://dx.doi.org/10.1128/AAC.05008-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468700PMC
July 2015

Evolution and dissemination of OqxAB-like efflux pumps, an emerging quinolone resistance determinant among members of Enterobacteriaceae.

Antimicrob Agents Chemother 2015 23;59(6):3290-7. Epub 2015 Mar 23.

Shenzhen Key Laboratory for Food Biological Safety Control, Food Safety and Technology Research Centre, Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong

The OqxAB efflux pump, a plasmid-mediated quinolone resistance (PMQR) determinant, has become increasingly prevalent among members of Enterobacteriaceae over the past decade. To investigate the evolution and dissemination routes of the oqxAB operon, we assessed the prevalence of oqxAB-like elements among various Gram-negative bacterial species and analyzed the genotypic and phenotypic characteristics of organisms harboring such elements. With a comprehensive genotyping approach, a chromosome-based oqxAB operon was detectable in all Klebsiella pneumoniae strains tested, including organisms isolated before the year 1984. Sequence and phylogenetic analyses confirmed that the oqxAB operon in K. pneumoniae isolates was genetically closest to their plasmid-borne counterparts recoverable only from Escherichia coli and Salmonella isolates collected from the year 2003 onward. Chromosomal elements with much lower sequence homology were also found among the Enterobacter spp. but not other Gram-negative species. Contrary to the quinolone resistance phenotypes which were consistently observable among organisms with oqxAB-harboring plasmids, chromosomal oqxAB elements generally did not confer quinolone resistance, except for K. pneumoniae strains, which exhibited a typical oqxAB-mediated phenotype characterized by cross-resistance to olaquindox, chloramphenicol, and the quinolones. Gene expression analysis illustrated that such phenotypes were due to elevated expression of the chromosomal oqxAB operon. Furthermore, transposition of the oqxAB operon from the bacterial chromosome to plasmids was found to result in a >80-fold increase in the level of expression of the OqxAB pump, confirming its status as the first constitutively expressed efflux system located in bacterial mobile elements.
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http://dx.doi.org/10.1128/AAC.00310-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432112PMC
February 2016

Complete nucleotide sequence of a conjugative plasmid carrying bla(PER-1).

Antimicrob Agents Chemother 2015 16;59(6):3582-4. Epub 2015 Mar 16.

Shenzhen Key Lab for Food Biological Safety Control, Food Safety and Technology Research Center, Hong Kong PolyU Shen Zhen Research Institute, Shenzhen, People's Republic of China State Key Lab of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong

The nucleotide sequence of a self-transmissible plasmid pVPH1 harboring bla(PER-1) from Vibrio parahaemolyticus was determined. pVPH1 was 183,730 bp in size and shared a backbone similar to pAQU1 and pAQU2, differing mainly in an ∼40-kb multidrug resistance (MDR) region. A complex class 1 integron was identified together with ISCR1 and bla(PER-1) (ISCR1-bla(PER-1)-gst-abct-qacEΔ1-sul1), which was shown to form a circular intermediate playing an important role in the dissemination of bla(PER-1).
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http://dx.doi.org/10.1128/AAC.00518-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432139PMC
March 2016

Identification and characterisation of a novel plasmid-mediated quinolone resistance gene, qnrVC7, in Vibrio cholerae of seafood origin.

Int J Antimicrob Agents 2015 Jun 23;45(6):667-8. Epub 2015 Feb 23.

Shenzhen Key Lab for Food Biological Safety Control, Food Safety and Technology Research Center, Hong Kong PolyU Shen Zhen Research Institute, Shenzhen, PR China; State Key Laboratory of Chirosciences, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong. Electronic address:

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http://dx.doi.org/10.1016/j.ijantimicag.2015.02.002DOI Listing
June 2015

Emergence of clinical Salmonella enterica serovar Typhimurium isolates with concurrent resistance to ciprofloxacin, ceftriaxone, and azithromycin.

Antimicrob Agents Chemother 2014 Jul 21;58(7):3752-6. Epub 2014 Apr 21.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR Food Safety and Technology Research Center, Hong Kong PolyU Shenzhen Research Institute, Shenzhen, People's Republic of China

Salmonella infection is an important public health issue for which the needs of antimicrobial treatment are increasing. A total of 546 human clinical S. enterica serovar Typhimurium isolates were recovered from patients in hospitals in China during the period of 2005 to ∼ 2011. Twenty percent of the isolates exhibited resistance to ciprofloxacin, and 4% were resistant to ceftriaxone. Importantly, for the first time, 12 (2%) S. Typhimurium isolates resistant to both ciprofloxacin and ceftriaxone were recovered; among these 12 isolates, two were also resistant to azithromycin, and one was resistant to all other drugs tested. The combined effects of various transferrable extended-spectrum β-lactamase determinants and a novel efflux-based ciprofloxacin resistance mechanism encoded by the mobile efflux gene oqxAB were responsible for the emergence of these extremely (highly) drug-resistant (XDR) S. Typhimurium isolates. The dissemination of resistance genes, such as those encoding ESBLs and the OqxAB pump, among Salmonella organisms will speed up the selection of XDR Salmonella, posing a huge threat to public health and Salmonella infection control.
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http://dx.doi.org/10.1128/AAC.02770-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068579PMC
July 2014

Molecular characterisation of a multidrug resistance conjugative plasmid from Vibrio parahaemolyticus.

Int J Antimicrob Agents 2013 Dec 1;42(6):575-9. Epub 2013 Oct 1.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong; Food Safety and Technology Research Center, Hong Kong PolyU Shenzhen Research Institute, Shenzhen, PR China.

Vibrio parahaemolyticus is a major causative agent of gastroenteritis and is the leading cause of food-borne illness in Hong Kong. Recent studies of resistance to extended-spectrum β-lactams and fluoroquinolones in V. parahaemolyticus have caused huge concern. This work reports the characterisation of a multidrug resistance conjugative plasmid in V. parahaemolyticus isolated from shrimp samples from Hong Kong. The plasmid is ca. 200 kb and carries multidrug resistance genes, including a novel plasmid-mediated quinolone resistance gene qnrVC6 surrounded by several known and novel insertion sequence (IS) elements, an extended-spectrum β-lactamase gene bla(PER-1) mediated by ISCR1, and a ca. 3-kb four-gene cassette (aacA3, catB2, dfrA1 and aadA1) class 1 integron. Transmission of this multidrug resistance conjugative plasmid among Vibrio spp. would compromise the effectiveness of Vibrio infection control and pose a huge threat to public health.
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http://dx.doi.org/10.1016/j.ijantimicag.2013.08.014DOI Listing
December 2013

Expansion of Salmonella enterica Serovar Typhimurium ST34 Clone Carrying Multiple Resistance Determinants in China.

Antimicrob Agents Chemother 2013 Sep 24;57(9):4599-4601. Epub 2013 Jun 24.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR

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http://dx.doi.org/10.1128/AAC.01174-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754352PMC
September 2013

Mechanisms of fluoroquinolone resistance in Vibrio parahaemolyticus.

Int J Antimicrob Agents 2013 Aug 7;42(2):187-8. Epub 2013 Jun 7.

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http://dx.doi.org/10.1016/j.ijantimicag.2013.04.024DOI Listing
August 2013

Characterization of multidrug-resistant Proteus mirabilis isolated from chicken carcasses.

Foodborne Pathog Dis 2013 Feb 25;10(2):177-81. Epub 2013 Jan 25.

Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR.

This study investigated genotypic and phenotypic features of antimicrobial resistance of Proteus mirabilis isolated from chicken products. Resistance to a broad spectrum of antimicrobial agents was commonly observed in the test isolates: tetracycline (100%), sulfamethoxazole (80%), chloramphenicol (66%), nalidixic acid (66%), ampicillin (60%), streptomycin (56%), ciprofloxacin (52%), kanamycin (46%), gentamicin (38%), ceftriaxone (36%), cefotaxime (34%), ceftiofur (22%), and amoxicillin-clavulanic acid (16%). The β-lactamases TEM-1 and OXA-1, and extended-spectrum β-lactamases CTX-M-9 and CMY-2 were detected in β-lactam-resistant isolates. Single mutations in gyrA and parC were found to be contributing factors for fluoroquinolone resistance. Plasmid-mediated quinolone resistance (PMQR) genes qnrA and qnrD were detected in six fluoroquinolone-resistant isolates and a superintegron element, SXT, was detected in 14 out of 50 isolates. The high-level of antimicrobial resistance of P. mirabilis isolated from food products may pose a potential threat to public health.
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http://dx.doi.org/10.1089/fpd.2012.1303DOI Listing
February 2013

Characterization of Salmonella food isolates with concurrent resistance to ceftriaxone and ciprofloxacin.

Foodborne Pathog Dis 2013 Jan;10(1):42-6

Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.

Foodborne salmonellosis is an important public health problem worldwide. Most human Salmonella infections occur through the consumption of contaminated food of animal origin. The study reported the first isolation of two Salmonella enterica serovar Oranienburg strains from pork in China with concurrent resistance to ciprofloxacin and ceftriaxone. Both isolates also showed resistance to norfloxacin, trimethoprim-sulfamethoxazole, and chloramphenicol, and an elevated minimal inhibitory concentraton of azithromycin; one strain was also resistant to amikacin, gentamicin, tetracycline, and amoxicillin-clavulanic acid. Salmonella ceftriaxone resistance was due to the production of IncN plasmidborne CTX-M-14 ESBL, and their ciprofloxacin resistance was mediated by target mutations and efflux pump activity. This is the first time that ceftriaxone- and ciprofloxacin-resistant Salmonella was reported in meat products, which may be due to the uses of antibiotics in animal production. The study warrants the continuous surveillance of multidrug-resistant Salmonella in meat products and cautious use of antibiotics in food animals.
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http://dx.doi.org/10.1089/fpd.2012.1266DOI Listing
January 2013

First detection of oqxAB in Salmonella spp. isolated from food.

Antimicrob Agents Chemother 2013 Jan 12;57(1):658-60. Epub 2012 Nov 12.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, SAR.

Food-borne salmonellosis is an important public health problem worldwide and the second leading cause of food-borne illnesses in Hong Kong. In this study, the prevalence and antimicrobial resistance of Salmonella in meat products in Hong Kong were determined. Interestingly, a plasmid-mediated quinolone resistance (PMQR) gene combination, oqxAB, which mediates resistance to nalidixic acid, chloramphenicol, and olaquindox, was for the first time detectable on the chromosomes of two Salmonella enterica serovar Derby isolates. Further surveillance of oqxAB in Salmonella will be needed.
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http://dx.doi.org/10.1128/AAC.01144-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3535962PMC
January 2013

Chlorogenic acid exhibits cholesterol lowering and fatty liver attenuating properties by up-regulating the gene expression of PPAR-α in hypercholesterolemic rats induced with a high-cholesterol diet.

Phytother Res 2013 Apr 6;27(4):545-51. Epub 2012 Jun 6.

Food Safety and Technology Research Centre, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, SAR, China.

Hypercholesterolemia is a major risk factor for the development of cardiovascular disease and nonalcoholic fatty liver disease. Natural compounds have been proved to be useful in lowering serum cholesterol to slow down the progression of cardiovascular disease and nonalcoholic fatty liver disease. In the present study, the hypocholesterolemic and hepatoprotective effects of the dietary consumption of chlorogenic acid were investigated by monitoring plasma lipid profile (total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein) in Sprague-Dawley rats fed with a normal diet, a high-cholesterol diet or a high-cholesterol diet supplemented with chlorogenic acid (1 or 10 mg/kg/day p.o.) for 28 days. Chlorogenic acid markedly altered the increased plasma total cholesterol and low-density lipoprotein but decreased high-density lipoprotein induced by a hypercholesterolemic diet with a dose-dependent improvement on both atherogenic index and cardiac risk factor. Lipid depositions in liver were attenuated significantly in hypercholesterolemic animals supplemented with chlorogenic acid. It is postulated that hypocholesterolemic effect is the primary beneficial effect given by chlorogenic acid, which leads to other secondary beneficial effects such as atheroscleroprotective, cardioprotective and hepatoprotective functions. The hypocholesterolemic functions of chlorogenic acid are probably due to the increase in fatty acids unitization in liver via the up-regulation of peroxisome proliferation-activated receptor α mRNA.
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http://dx.doi.org/10.1002/ptr.4751DOI Listing
April 2013
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