The molecular basis, and biological cost, of fluoroquinolone resistance in Salmonella enterica serovar Paratyphi A.

Lead Research Organisation: Public Health England
Department Name: Microbiology Services (MS) Colindale

Abstract

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Technical Summary

Specific control measures for enteric fever; vaccination and antibiotic treatment, are designed to limit the spread of Salmonella Typhi (typhoid fever). An increasing number of cases of enteric fever however are being caused by S. Paratyphi A (paratyphoid fever). There is no evidence that typhoid fever protects against paratyphoid fever and so the currently available S. Typhi specific vaccines are not expected to protect against S. Paratyphi A. As well as a lack of a vaccine there has been an increase in antibiotic resistance. In particular a decrease in susceptibility to fluoroquinolones has been associated with an increase in cases of paratyphoid across Asia. Full fluoroquinolone resistance in S. Paratyphi A, has now emerged and is spreading. The two sequenced isolates of S. Paratyphi A, are very closely related at the nucleotide level and so a detailed analysis of antibiotic resistant and susceptible strains will allow us to investigate all of the genetic events involved in the emergence of fluoroquinolone resistance in this important human pathogen. Identification of genetic markers has allowed the early detection of resistant S. Paratyphi A strains and collaborative laboratories in China, Pakistan and India are collecting resistant strains as they are isolated. By phenotypic and genetic analysis of these isolates we will identify genetic factors which will be introduced into isogenic mutants using technology developed in the laboratory of principal applicant. This will allow a detailed study of the contribution of different mutations (or gene acquisition) to fluoroquinolone resistance in the S. Paratyphi A background. The co-applicants expertise in the biology of efflux mechanisms of resistance, and the quality of the two postdoctoral scientists is key to the success of this project which is of fundamental importance to understanding how resistance to the fluoroquinolones, a very important group of antibacterial agents, evolves in Salmonella enterica, an important human and animal pathogen.

Publications

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Paglietti B (2013) Diversity among human non-typhoidal salmonellae isolates from Zimbabwe. in Transactions of the Royal Society of Tropical Medicine and Hygiene

 
Description Wellcome Trust Frontiers meeting
Geographic Reach Africa 
Policy Influence Type Participation in advisory committee
Impact The Wellcome Trust is planning to launch an initiative to fund the use of technology to investigate antibiotic resistance in sub-Saharan Africa. The data generated from this project was presented at an Information gathering meeting in Cape Town.
 
Title Luminex assay for detecting resistance mutations in Salmonella Typhi and Paratyphi A 
Description A SNP detection assay using Luminex technology , published in: PMID: 20511368 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact The technique was the result of collaborative research with the University of Cork and represents a method which could be used for SNP detection in several pathogens. As a result of our experience we are currently developing assays for sub-typing of Salmonella enterica. 
URL http://europepmc.org/abstract/MED/20511368
 
Title Wt Strains CipR 
Description Isogenic bacterial cultures containg defined mutations in topoisomerase genes encoding resistancec to fluoroquinolones 
Type Of Material Cell line 
Year Produced 2012 
Provided To Others? Yes  
Impact Publication - PMID:16895934 
URL http://europepmc.org/abstract/MED/16895934
 
Description Developing MLST as an alternative to serotyping for Salmonella 
Organisation University College Cork
Department Environmental Research Institute
Country Ireland 
Sector Academic/University 
PI Contribution Selection od strains for MLST, performing MLSt and selection of SNPs invovled in fluoroquinolones resistance.
Collaborator Contribution Database curation for the MLST database, design and performance of assays for detection of bacterial SNPs involved in fluoroquinolones resistance
Impact Publication on SNP typing assay PMID 20511368 MLST database for Salonella at www.mlst.net
 
Description Hong-Xia visit 
Organisation South China Agricultural University
Country China 
Sector Academic/University 
PI Contribution Host for visiting scientist/ anlaysis of data
Collaborator Contribution Data anlaysis
Impact Manuscript submitted and visit of Chinese scientist to UK
Start Year 2009
 
Description Salmonella Paratyphi A in southern China 
Organisation Guangxi Centre for Disease Control and Prevention
Department Department of Bacteriology
Country China 
Sector Public 
PI Contribution Advice to Chinese collaborators on research direction, analysis of isolates for phenotypic and genotypic characteristics involved in antibiotic resistance
Collaborator Contribution Provision of strains and intellectual input
Impact Poster: Nair, S., Yang, J., Ochiai, RL., Wang, ML., Hasan, R., Bhutta, Z., Dong, BQ,. Wain,J. Drug resistance patterns of S. ParatyphiA and S. Typhi in Southern China and Karachi,Pakistan. British Society for Antimicrobial Chemotheraphy. Antibiotic Resistance Mechanisms. Workshop for Researchers. 9-10 Nov 2006.
Start Year 2008