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Updated: Oct 18, 2025
High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
The molecular basis of extensively drug-resistant Salmonella Typhi isolates from pediatric septicemia patients
Chanmi Kim1, Iqra Latif2, Durga P Neupane1
1Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Insights
Extensively drug-resistant Salmonella Typhi is a growing threat in pediatric sepsis. This study reveals key antibiotic resistance genes in XDR S. Typhi isolates from children, informing new detection and treatment strategies.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Sepsis, a life-threatening response to infection, poses a significant public health challenge, especially in developing nations.
- Salmonella Typhi (S. Typhi) is a major cause of pediatric sepsis in typhoid-endemic regions, with extensively drug-resistant (XDR) strains increasingly prevalent in children.
- Existing antibiotic resistance studies often focus on adult S. Typhi isolates, leaving a gap in understanding pediatric resistance patterns.
Purpose of the Study:
- To characterize the antibiotic resistance profiles of XDR S. Typhi isolates from a cohort of pediatric typhoid patients.
- To identify antibiotic resistance-related gene signatures associated with common treatment options for S. Typhi infections in children.
- To elucidate the molecular basis of antibiotic resistance in pediatric XDR S. Typhi.
Main Methods:
- Antibiotic resistance profiles of 45 XDR S. Typhi isolates from pediatric patients (ages 1-13) were characterized.
- Specific genes associated with multidrug resistance (blaTEM1, dhfR7, sul1, catA1), fluoroquinolone resistance (qnrS, gyrA, gyrB, parC, parE), XDR (blaCTX-M-15), and efflux pumps (macAB, acrAB) were analyzed in 18 representative isolates.
- Genotypic analysis was correlated with phenotypic antibiotic resistance.
Main Results:
- The study identified specific genetic markers, including blaTEM1, dhfR7, sul1, catA1, qnrS, blaCTX-M-15, and a gyrA point mutation, correlating with the observed multidrug and extensively drug-resistant phenotypes in pediatric S. Typhi isolates.
- The genotypic findings confirmed the molecular basis for the antibiotic resistance observed in the clinical isolates.
- A significant prevalence of XDR S. Typhi was noted among the pediatric cohort.
Conclusions:
- This research provides critical insights into the molecular mechanisms underlying antibiotic resistance in S. Typhi strains affecting pediatric populations.
- The findings can aid in the development of targeted molecular detection methods for XDR S. Typhi in children.
- Understanding these resistance patterns is crucial for informing effective treatment strategies and combating the rise of XDR typhoid fever in pediatric patients.
Abstract:
Sepsis is a syndromic response to infections and is becoming an emerging threat to the public health sector, particularly in developing countries. Salmonella Typhi (S. Typhi), the cause of typhoid fever, is one primary cause of pediatric sepsis in typhoid endemic areas. Extensively drug-resistant (XDR) S. Typhi is more common among pediatric patients, which is responsible for over 90% of the reported XDR typhoid cases, but the majority of antibiotic resistance studies available have been carried out using S. Typhi isolates from adult patients. Here, we characterized antibiotic-resistance profiles of XDR S. Typhi isolates from a medium size cohort of pediatric typhoid patients (n = 45, 68.89% male and 31.11% female) and determined antibiotic-resistance-related gene signatures associated with common treatment options to typhoid fever patients of 18 XDR S. Typhi representing all 45 isolates. Their ages were 1-13 years old: toddlers aging 1-2 years old (n = 9, 20%), pre-schoolers aging 3-5 years old (n = 17, 37.78%), school-age children aging 6-12 years old (n = 17, 37.78%), and adolescents aging 13-18 years old (n = 2, 4.44%). Through analyzing blaTEM1, dhfR7, sul1, and catA1genes for multidrug-resistance, qnrS, gyrA, gyrB, parC, and parE for fluoroquinolone-resistance, blaCTX-M-15 for XDR, and macAB and acrAB efflux pump system-associated genes, we showed the phenotype of the XDR S. Typhi isolates matches with their genotypes featured by the acquisitions of the genes blaTEM1, dhfR7, sul1, catA1, qnrS, and blaCTX-M-15 and a point mutation on gyrA. This study informs the molecular basis of antibiotic-resistance among recent S. Typhi isolates from pediatric septicemia patients, therefore providing insights into the development of molecular detection methods and treatment strategies for XDR S. Typhi.
