Publications by authors named "Edward Wai Chi Chan"

The emergence and rapid dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) pose a serious threat to public health. Antibiotic treatment failure of K. pneumoniae infections has been largely attributed to acquisition of antibiotic resistance and bacterial biofilm caused by the presence of antibiotic persisters.

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Since animal growth promoters (AGPs) are used in large quantities and commonly released to the environment from animal farms, it is necessary to determine whether such agents should be regarded as an environmental toxin that poses a threat to the ecosystem and health risk to wildlife. In this study, a multi-omics approach was employed to explore the effects of a representative AGP, lincomycin, on key metabolic and physiological functions of animals, using a mouse model. The results indicated that exposure to lincomycin resulted in a significant increase in growth rate of mice (50.

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Polymyxins, including colistin and polymyxin B, serve as crucial last-resort antibiotics for managing infections caused by carbapenem-resistant Enterobacterales (CRE). However, the rapid spread of the mobilized colistin resistance gene (mcr-1) challenged the efficacy of treatment by polymyxins. The mcr-1 gene encoded a transmembrane phosphoethanolamine (PEA) transferase enzyme, MCR-1.

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Bacterial antibiotic tolerance is a decades-old phenomenon in which a bacterial sub-population, commonly known as persisters, does not respond to antibiotics and remains viable upon prolonged antimicrobial treatment. Persisters are detectable in populations of bacterial strains that are not antibiotic-resistant and are known to be responsible for treatment failure and the occurrence of chronic and recurrent infection. The clinical significance of antibiotic tolerance is increasingly being recognized and comparable to antibiotic resistance.

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Article Synopsis
  • The study addresses the challenge of multidrug-resistant Acinetobacter baumannii (Ab) infections, which are linked to high mortality rates, and aims to uncover strategies for better management.
  • Researchers used various methodologies including flow cytometry and RNA sequencing to investigate the immune response during Ab sepsis, focusing on the role of macrophages in driving severe inflammation.
  • The results reveal that macrophages contribute to a dangerous cytokine storm, regulated by a specific signaling pathway, and that the drug naproxen can protect against fatal infections by mitigating these inflammatory responses.
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Klebsiella pneumoniae (Kp) is increasingly recognized as a reservoir for a range of antibiotic resistance genes and a pathogen that frequently causes severe infections in both hospital and community settings. In this study, we have identified a novel mechanism of conjugative transfer of a non-conjugative virulence plasmid through the formation of a fusion plasmid between the virulence plasmid and a novel 59,162 bp IncN- plasmid. This plasmid was found to be a multidrug-resistance (MDR) plasmid and carried a T4SS cluster, which greatly facilitated the efficient horizontal transfer of the fusion plasmid between Kp strains.

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Vibrio spp., known as significant marine pathogens, have become more prevalent due to global warming. Antibiotics released into the environment drive Vibrio resistance.

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The emergence of plasmid-encoded colistin resistance mechanisms, MCR-1, a phosphoethanolamine transferase, rendered colistin ineffective as last resort antibiotic against severe infections caused by clinical Gram-negative bacterial pathogens. Through screening FDA-approved drug library, we identified two structurally similar compounds, namely cetylpyridinium chloride (CET) and domiphen bromide (DOM), which potentiated colistin activity in both colistin-resistant and susceptible Enterobacterales. These compounds were found to insert their long carbon chain to a hydrophobic pocket of bacterial phosphoethanolamine transferases including MCR-1, competitively blocking the binding of lipid A tail for substrate recognition and modification, resulting in the increase of bacterial sensitivity to colistin.

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Article Synopsis
  • * Various experiments showed that AN2178 not only restored the effectiveness of the antibiotic meropenem against resistant strains but also improved survival rates in infected mice.
  • * Safety tests indicate that AN2178 is safe for clinical use, making it a promising treatment option for infections caused by multi-drug resistant bacteria, particularly those resistant to ceftazidime-avibactam.
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Acinetobacter baumannii (AB) infections have become a global public health concern due to the continued increase in the incidence of infection and the rate of resistance to carbapenems. This study aimed to investigate the genomic features of AB strains recovered from a tertiary hospital and assess the clinical implications of the findings. A total of 217 AB strains were collected between 2016 and 2018 at a tertiary hospital in Guangzhou, with 183 (84.

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Gut damage during carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-HvKP) infection is associated with a death risk. Understanding the mechanisms by which CR-HvKP causes intestinal damage and gut microbiota alteration, and the impact on immunity, is crucial for developing therapeutic strategies. This study investigated if gastrointestinal tract damage and disruption of gut microbiota induced by CR-HvKP infection undermined host immunity and facilitated multi-organ invasion of CR-HvKP; whether the therapeutic value of the rifampicin (RIF) and zidovudine (ZDV) combination was attributed to their ability to repair damages and restore host immunity was determined.

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The tigecycline resistance gene tet(X4) has been widely reported in animals and animal products in some Asian countries including China in recent years but only sporadically detected in human. In this study, we investigated the prevalence and genetic features of tet(X4)-positive clinical E. coli strains.

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Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a global threat due to its high mortality in clinical patients. However, the specific mechanisms underlying this increased mortality remain unclear. The objective of this study is to investigate how the development of a resistance phenotype contributes to the significantly higher mortality associated with this pathogen.

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Article Synopsis
  • - This study analyzed 21 non-O1/non-O139 V. cholerae strains from food samples in Guangdong, revealing high resistance rates to antibiotics like nalidixic acid and ampicillin, with the gene qnrVC found in most isolates.
  • - Important mutations linked to quinolone resistance were identified in 47.62% of the strains, highlighting the genetic mechanisms behind their antibiotic resistance.
  • - Although the strains lacked key toxigenic genes associated with severe cholera, they contained other toxin-related genes and showed genetic links to clinical strains, raising concerns about their potential to infect humans.
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4,[5],12:i:-, a monophasic variant of Typhimurium, has emerged as a global cause of multidrug-resistant salmonellosis and has become endemic in many developing and developed countries, especially in China. Here, we have sequenced 352 clinical isolates in Guangdong, China, during 2009-2019 and performed a large-scale collection of 4,[5],12:i:- with whole genome sequencing (WGS) data across the globe, to better understand the population structure, antimicrobial resistance (AMR) genomic characterization, and transmission routes of 4,[5],12:i:- across Guangdong. 4,[5],12:i:- strains showed broad genetic diversity; Guangdong isolates were found to be widely distributed among the global lineages.

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The escalating prevalence of multidrug-resistant (MDR) bacteria pose a significant public health threat. Understanding the genomic features and deciphering the antibiotic resistance profiles of these pathogens is crucial for development of effective surveillance and treatment strategies. In this study, we employed the R10.

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Antibiotic resistance is a global health issue, with Klebsiella pneumoniae (KP) posing a particular threat due to its ability to acquire resistance to multiple drug classes rapidly. OXA-232 is a carbapenemase that confers resistance to carbapenems, a class of antibiotics often used as a last resort for treating severe bacterial infections. The study reports the earliest known identification of six OXA-232-producing KP strains that were isolated in Zhejiang, China, in 2008 and 2009 within a hospital, two years prior to the first reported identification of OXA-232 in France.

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The erm(T) gene encodes the 23 s rRNA methyltransferase and confers erythromycin resistance in Gram-positive bacteria, while has rarely been identified in Gram-negative bacteria. In this study, we identified a small IncQ1 plasmid of 6135 bp harboring the erm(T) gene in a clinical K. pneumoniae strain and confirmed the role of the erm(T) gene in mediating azithromycin resistance.

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Background: The epidemiological features of the Klebsiella pneumoniae causing bloodstream infections in Hong Kong and their potential threats to human health remained unknown.

Methods: K. pneumoniae strains collected from four hospitals in Hong Kong during the period of 2009-2018 were subjected to molecular typing, string test, antimicrobial susceptibility testing, whole genome sequencing and analysis.

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The emergence of carbapenem-resistant hypervirulent (CR-hvKP) poses grave threats to human health. These strains increased dramatically in clinical settings in China in the past few years but not in other parts of the world. Four isogenic strains, including classical , carbapenem-resistant (CRKP), hypervirulent (hvKP) and CR-hvKP, were created and subjected to phenotypic characterization, competition assays, mouse sepsis model and rat colonization tests to investigate the mechanisms underlying the widespread nature of CR-hvKP in China.

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The global transmission of carbapenem-resistant Acinetobacter baumannii (CRAB) poses a significant and grave threat to human health. To investigate the potential relationship between hospital sewage and the transmission of CRAB within healthcare facilities, isolates of Acinetobacter spp. obtained from untreated hospital sewage samples were subjected to antimicrobial susceptibility tests, genome sequencing, and bioinformatic and phylogenetic tree analysis, and that data were matched with those of the clinical isolates.

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Klebsiella pneumoniae is an important clinical bacterial pathogen that has hypervirulent and multidrug-resistant variants. Uniform Manifold Approximation and Projection (UMAP) was used to cluster genomes of 16 797 K. pneumoniae strains collected, based on core genome distance, in over 100 countries during the period 1937 to 2021.

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