Investigation of Virulence Genes Detected in Antimicrobial-Resistance Pathogens Isolates for Five Countries across the World

Cui, Kevin; Gong, Iris; Dong, Alvin; Yan, Jacob; Wang, Max; Huang, Zuyi

doi:10.3390/pr8121589

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…Enhancements in any of these areas can yield favorable effects in the treatment of L. monocytogenes . For instance, anti-virulence medications targeting specific virulence factors could serve as viable alternatives to traditional antibiotic therapies [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Druggability Analysis of Protein Targets for Drug Discovery to Combat Listeria monocytogenes

Hanes,

Liu,

Huang

2024

Microorganisms

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Extensive research has been conducted to identify key proteins governing stress responses, virulence, and antimicrobial resistance, as well as to elucidate their interactions within Listeria monocytogenes. While these proteins hold promise as potential targets for novel strategies to control L. monocytogenes, given their critical roles in regulating the pathogen’s metabolism, additional analysis is needed to further assess their druggability—the chance of being effectively bound by small-molecule inhibitors. In this work, 535 binding pockets of 46 protein targets for known drugs (mainly antimicrobials) were first analyzed to extract 13 structural features (e.g., hydrophobicity) in a ligand–protein docking platform called Molsoft ICM Pro. The extracted features were used as inputs to develop a logistic regression model to assess the druggability of protein binding pockets, with a value of one if ligands can bind to the protein pocket. The developed druggability model was then used to evaluate 23 key proteins from L. monocytogenes that have been identified in the literature. The following proteins are predicted to be high-potential druggable targets: GroEL, FliH/FliI complex, FliG, FlhB, FlgL, FlgK, InlA, MogR, and PrfA. These findings serve as an initial point for future research to identify specific compounds that can inhibit druggable target proteins and to design experimental work to confirm their effectiveness as drug targets.

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Section: Introductionmentioning

confidence: 99%

Druggability Analysis of Protein Targets for Drug Discovery to Combat Listeria monocytogenes

Hanes,

Liu,

Huang

2024

Microorganisms

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“…Obtaining AMR gene and resistance data over time in different locations is essential to provide a comprehensive view of AMR status in U.S. cattle. Fortunately, the NCBI Pathogen Detection Isolates Browser (NPDIB) provides the genotype data of pathogen isolates [22][23][24]. Additional information on pathogen isolates, such as the sampling location, the sampling date, and isolation sources, is also included.…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Study of Historical Detection Data for Pathogen Isolates from U.S. Cattle

Gu,

Pei,

Zhou

et al. 2023

Antibiotics

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Foodborne pathogens pose substantial health hazards and result in considerable economic losses in the U.S. Fortunately, the National Center for Biotechnology Information Pathogen Detection Isolates Browser (NPDIB) provides valuable access to antimicrobial resistance (AMR) genes and antimicrobial assay data. This study aimed to conduct the first comprehensive investigation of AMR genes in pathogens isolated from U.S. cattle over the past decade, driven by the urgent need to address the dangers of AMR specifically originating in pathogens isolated from U.S. cattle. In this study, around 28,000 pathogen isolate samples were extracted from the NPDIB and then analyzed using multivariate statistical methods, mainly principal component analysis (PCA) and hierarchical clustering (H-clustering). These approaches were necessary due to the high dimensions of the raw data. Specifically, PCA was utilized to reduce the dimensions of the data, converting it to a two-dimensional space, and H-clustering was used to better identify the differences among data points. The findings from this work highlighted Salmonella enterica and Escherichia coli as the predominant pathogens among the isolates, with E. coli being the more concerning pathogen due to its increasing prevalence in recent years. Moreover, tetracycline was observed as the most commonly resistant antimicrobial, with the resistance genes mdsA, mdsB, mdtM, blaEC, and acrF being the most prevalent in pathogen isolates from U.S. cattle. The occurrence of mdtM, blaEC, acrF, and glpT_E448k showed an increase in pathogens isolated from U.S. cattle in recent years. Furthermore, based on the data collected for the locations of AMR cases, Texas, California, and Nebraska were the major areas carrying major AMR genes or antimicrobials with detected resistance. The results from this study provide potential directions for targeted interventions to mitigate pathogens’ antimicrobial resistance in U.S. cattle.

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“…The National Centre for Biotechnology Information Pathogens Isolates Browser (NPIB) database offers sensitive and rapid surveillance with enhanced methods of laboratory identification and subtyping for foodborne pathogens. In addition, it identifies antimicrobial resistance genes, stress response genes, and virulence genes for each isolate sample [32,33]. Research for each type of gene for microorganisms from the NPIB has been conducted to some extent.…”

Section: Introductionmentioning

confidence: 99%

“…As for antimicrobial resistance, genes are mainly involved in antimicrobialdegradation, antimicrobial efflux pumps, and modification of antimicrobial binding targets [32]. It was reported by Cui et al, 2021 that virulence factors facilitate pathogens to infect host cells with adhesin-like proteins, increased iron reception and uptake, and toxin synthesis for host inhibition [33]. As for stress response genes, the following operons/genes are reported as important: the mer operon (responsible for the regulation of mercury binding and resistance), the ars operon (which mediates arsenic resistance), and asr (which regulates an acid shock protein that allows for survival in acidic conditions) [34].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Genes Involved in the Outbreaks of Escherichia coli and Salmonella spp. in the United States

Wang

Tang

et al. 2021

Antibiotics

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Salmonella spp. and Escherichiacoli (E. coli) are two of the deadliest foodborne pathogens in the US. Genes involved in antimicrobial resistance, virulence, and stress response, enable these pathogens to increase their pathogenicity. This study aims to examine the genes detected in both outbreak and non-outbreak Salmonella spp. and E. coli by analyzing the data from the National Centre for Biotechnology Information (NCBI) Pathogen Detection Isolates Browser database. A multivariate statistical analysis was conducted on the genes detected in isolates of outbreak Salmonella spp., non-outbreak Salmonella spp., outbreak E. coli, and non-outbreak E. coli. The genes from the data were projected onto a two-dimensional space through principal component analysis. Hierarchical clustering was then used to quantify the relationship between the genes in the dataset. Most of the outlier genes identified in E. coli isolates are virulence genes, while outlier genes identified in Salmonella spp. are mainly involved in stress response. Gene epeA, which encodes a high-molecular-weight serine protease autotransporter of Enterobacteriaceae (SPATE) protein, along with subA and subB that encode cytotoxic activity, may contribute to the pathogenesis of outbreak E. coli. The iro operon and ars operon may play a role in the ecological success of the epidemic clones of Salmonella spp. Concurrent relationships between esp and ter operons in E. coli and pco and sil operons in Salmonella spp. are found. Stress-response genes (asr, golT, golS), virulence gene (sinH), and antimicrobial resistance genes (mdsA and mdsB) in Salmonella spp. also show a concurrent relationship. All these findings provide helpful information for experiment design to combat outbreaks of E. coli and Salmonella spp.

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Investigation of Virulence Genes Detected in Antimicrobial-Resistance Pathogens Isolates for Five Countries across the World

Cited by 6 publications

References 35 publications

Druggability Analysis of Protein Targets for Drug Discovery to Combat Listeria monocytogenes

Druggability Analysis of Protein Targets for Drug Discovery to Combat Listeria monocytogenes

A Comprehensive Study of Historical Detection Data for Pathogen Isolates from U.S. Cattle

Investigation of the Genes Involved in the Outbreaks of Escherichia coli and Salmonella spp. in the United States

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