Dataset Information

Bacteriophage ZCSE2 is a Potent Antimicrobial Against Salmonella enterica Serovars: Ultrastructure, Genomics and Efficacy.

ABSTRACT: Developing novel antimicrobials capable of controlling multidrug-resistant bacterial pathogens is essential to restrict the use of antibiotics. Bacteriophages (phages) constitute a major resource that can be harnessed as an alternative to traditional antimicrobial therapies. Phage ZCSE2 was isolated among several others from raw sewage but was distinguished by broad-spectrum activity against Salmonella serovars considered pathogenic to humans and animals. Lytic profiles of ZCSE2 against a panel of Salmonella were determined together with low temperature activity and pH stability. The morphological features of the phage and host infection processes were characterized using a combination of transmission electron and atomic force microscopies. Whole genome sequencing of ZCSE2 produced a complete DNA sequence of 53,965 bp. No known virulence genes were identified in the sequence data, making ZCSE2 a good candidate for phage-mediated biological control purposes. ZCSE2 was further tested against S. Enteritidis in liquid culture and was observed to reduce the target bacterium to below the limits of detection from initial concentrations of 107-108 Colony Forming Units (CFU)/mL. With a broad host-range against pathogenic Salmonella serovars, phage ZCSE2 constitutes a potential tool against a major cause of human and animal disease.

SUBMITTER: Mohamed A

PROVIDER: S-EPMC7232530 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

Bacteriophage ZCSE2 is a Potent Antimicrobial Against <i>Salmonella enterica</i> Serovars: Ultrastructure, Genomics and Efficacy.

Mohamed Ahmed A Taha Omar O El-Sherif Hesham M HM Connerton Phillippa L PL Hooton Steven P T SPT Bassim Nabil D ND Connerton Ian F IF El-Shibiny Ayman A El-Shibiny Ayman A

Viruses 20200409 4

Developing novel antimicrobials capable of controlling multidrug-resistant bacterial pathogens is essential to restrict the use of antibiotics. Bacteriophages (phages) constitute a major resource that can be harnessed as an alternative to traditional antimicrobial therapies. Phage ZCSE2 was isolated among several others from raw sewage but was distinguished by broad-spectrum activity against <i>Salmonella</i> serovars considered pathogenic to humans and animals. Lytic profiles of ZCSE2 against a ...[more]

PMID: 32283768

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Project description:Nontyphoidal Salmonella (NTS) is a leading global cause of bacterial foodborne morbidity and mortality. Our ability to treat severe NTS infections has been impaired by increasing antimicrobial resistance (AMR). To understand and mitigate the global health crisis AMR represents, we need to link the observed resistance phenotypes with their underlying genomic mechanisms. Broiler chickens represent a key reservoir and vector for NTS infections, but isolates from this setting have been characterized in only very low numbers relative to clinical isolates. In this study, we sequenced and assembled 97 genomes encompassing 7 serotypes isolated from broiler chicken in farms in British Columbia between 2005 and 2008. Through application of machine learning (ML) models to predict the observed AMR phenotype from this genomic data, we were able to generate highly (0.92 to 0.99) precise logistic regression models using known AMR gene annotations as features for 7 antibiotics (amoxicillin-clavulanic acid, ampicillin, cefoxitin, ceftiofur, ceftriaxone, streptomycin, and tetracycline). Similarly, we also trained "reference-free" k-mer-based set-covering machine phenotypic prediction models (0.91 to 1.0 precision) for these antibiotics. By combining the inferred k-mers and logistic regression weights, we identified the primary drivers of AMR for the 7 studied antibiotics in these isolates. With our research representing one of the largest studies of a diverse set of NTS isolates from broiler chicken, we can thus confirm that the AmpC-like CMY-2 β-lactamase is a primary driver of β-lactam resistance and that the phosphotransferases APH(6)-Id and APH(3″-Ib) are the principal drivers of streptomycin resistance in this important ecosystem.IMPORTANCE Antimicrobial resistance (AMR) represents an existential threat to the function of modern medicine. Genomics and machine learning methods are being increasingly used to analyze and predict AMR. This type of surveillance is very important to try to reduce the impact of AMR. Machine learning models are typically trained using genomic data, but the aspects of the genomes that they use to make predictions are rarely analyzed. In this work, we showed how, by using different types of machine learning models and performing this analysis, it is possible to identify the key genes underlying AMR in nontyphoidal Salmonella (NTS). NTS is among the leading cause of foodborne illness globally; however, AMR in NTS has not been heavily studied within the food chain itself. Therefore, in this work we performed a broad-scale analysis of the AMR in NTS isolates from commercial chicken farms and identified some priority AMR genes for surveillance.

Dataset Information

Bacteriophage ZCSE2 is a Potent Antimicrobial Against Salmonella enterica Serovars: Ultrastructure, Genomics and Efficacy.

Publications

Bacteriophage ZCSE2 is a Potent Antimicrobial Against <i>Salmonella enterica</i> Serovars: Ultrastructure, Genomics and Efficacy.

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