Loci for prediction of penicillin and tetracycline susceptibility in Neisseria gonorrhoeae: a genome-wide association study

Mortimer, Tatum D; Zhang, Jessica J; Kévin, C; Grad, Yonatan H.

doi:10.1016/s2666-5247(22)00034-9

Cited by 14 publications

(18 citation statements)

References 31 publications

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“…Furthermore, this approach allows the discovery of new AMR genes, or alleles of known AMR genes, as reported in various pathogenic bacteria [ 12 , 25 , 26 ]. Comparative genomics and genome-wide association studies (GWAS) have identified these potential causal variants associated with virulence and with AMR in multiple organisms [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

WGS-Based Lineage and Antimicrobial Resistance Pattern of Salmonella Typhimurium Isolated during 2000–2017 in Peru

et al. 2022

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Salmonella Typhimurium is associated with foodborne diseases worldwide, including in Peru, and its emerging antibiotic resistance (AMR) is now a global public health problem. Therefore, country-specific monitoring of the AMR emergence is vital to control this pathogen, and in these aspects, whole genome sequence (WGS)—based approaches are better than gene-based analyses. Here, we performed the antimicrobial susceptibility test for ten widely used antibiotics and WGS-based various analyses of 90 S. Typhimurium isolates (human, animal, and environment) from 14 cities of Peru isolated from 2000 to 2017 to understand the lineage and antimicrobial resistance pattern of this pathogen in Peru. Our results suggest that the Peruvian isolates are of Typhimurium serovar and predominantly belong to sequence type ST19. Genomic diversity analyses indicate an open pan-genome, and at least ten lineages are circulating in Peru. A total of 48.8% and 31.0% of isolates are phenotypically and genotypically resistant to at least one antibiotic, while 12.0% are multi-drug resistant (MDR). Genotype–phenotype correlations for ten tested drugs show >80% accuracy, and >90% specificity. Sensitivity above 90% was only achieved for ciprofloxacin and ceftazidime. Two lineages exhibit the majority of the MDR isolates. A total of 63 different AMR genes are detected, of which 30 are found in 17 different plasmids. Transmissible plasmids such as lncI-gamma/k, IncI1-I(Alpha), Col(pHAD28), IncFIB, IncHI2, and lncI2 that carry AMR genes associated with third-generation antibiotics are also identified. Finally, three new non-synonymous single nucleotide variations (SNVs) for nalidixic acid and eight new SNVs for nitrofurantoin resistance are predicted using genome-wide association studies, comparative genomics, and functional annotation. Our analysis provides for the first time the WGS-based details of the circulating S. Typhimurium lineages and their antimicrobial resistance pattern in Peru.

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Section: Introductionmentioning

confidence: 99%

WGS-Based Lineage and Antimicrobial Resistance Pattern of Salmonella Typhimurium Isolated during 2000–2017 in Peru

et al. 2022

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“…Mismatched methylation has been demonstrated to kill Neisseria which have recently integrated novel DNA into their chromosomes through restriction enzyme(s) cleavage and the formation of double-strand breaks ( 83 , 84 ). However, despite the aforementioned barriers, observable genome-wide recombination ( 14 , 22 , 85 ) and reports of specific alleles acquired across species’ borders ( 86 , 87 ) directly support the importance of commensals as reservoirs of readily available adaptive genetic variation for the pathogens within the genus.…”

Section: Dna Promiscuity: the Prevalence Of Allelic Exchangementioning

confidence: 99%

Canary in the Coal Mine: How Resistance Surveillance in Commensals Could Help Curb the Spread of AMR in Pathogenic Neisseria

Goytia

Wadsworth

2022

mBio

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“…Such diagnostics have been developed and deployed for a number of pathogens, including the detection of rifampin resistance-conferring mutations in rpoB in M. tuberculosis, 86 detection of mecA to identify methicillin-resistant Staphylococcus aureus, 87 and, recently, the development of a test for N. gonorrhoeae that reports on ciprofloxacin susceptibility by examining gyrA codon 91. 88 The vast amount of pathogen genome sequencing being performed and the links to phenotypic antibiotic susceptibility testing have prompted a surge of interest in using statistical methods to predict AST from nucleotide sequencing 52,72,80,[89][90][91][92][93][94] (Table 1). While the applications of machine learning tools are being explored in many bacterial pathogens, [95][96][97] diagnostics?…”

Section: Rapid Diagnostics That Predict Antimicrobial Susceptibilitymentioning

confidence: 99%

Machine learning models for Neisseria gonorrhoeae antimicrobial susceptibility tests

Martin

Mortimer

Grad

2022

Annals of the New York Academy of Sciences

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Neisseria gonorrhoeae is an urgent public health threat due to the emergence of antibiotic resistance. As most isolates in the United States are susceptible to at least one antibiotic, rapid molecular antimicrobial susceptibility tests (ASTs) would offer the opportunity to tailor antibiotic therapy, thereby expanding treatment options. With genome sequence and antibiotic resistance phenotype data for nearly 20,000 clinical N. gonorrhoeae isolates now available, there is an opportunity to use statistical methods to develop sequence-based diagnostics that predict antibiotic susceptibility from genotype. N. gonorrhoeae, therefore, provides a useful example illustrating how to apply machine learning models to aid in the design of sequence-based ASTs. We present an overview of this framework, which begins with establishing the assay technology, the performance criteria, the population in which the diagnostic will be used, and the clinical goals, and extends to the choices that must be made to arrive at a set of features with the desired properties for predicting susceptibility phenotype from genotype. While we focus on the example of N. gonorrhoeae, the framework generalizes to other organisms for which large-scale genotype and antibiotic resistance data can be combined to aid in diagnostics development.

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Loci for prediction of penicillin and tetracycline susceptibility in Neisseria gonorrhoeae: a genome-wide association study

Cited by 14 publications

References 31 publications

WGS-Based Lineage and Antimicrobial Resistance Pattern of Salmonella Typhimurium Isolated during 2000–2017 in Peru

WGS-Based Lineage and Antimicrobial Resistance Pattern of Salmonella Typhimurium Isolated during 2000–2017 in Peru

Canary in the Coal Mine: How Resistance Surveillance in Commensals Could Help Curb the Spread of AMR in Pathogenic Neisseria

Machine learning models for Neisseria gonorrhoeae antimicrobial susceptibility tests

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