Genomic signature of multidrug-resistant Salmonella enterica serovar typhi isolates related to a massive outbreak in Zambia between 2010 and 2012.
Retrospectively, we investigated the epidemiology of a massive Salmonella enterica serovar Typhi outbreak in Zambia during 2010 to 2012. Ninety-four isolates were susceptibility tested by MIC determinations. Whole-genome sequence typing (WGST) of 33 isolates and bioinformatic analysis identified the multilocus sequence type (MLST), haplotype, plasmid replicon, antimicrobial resistance genes, and genetic relatedness by single nucleotide polymorphism (SNP) analysis and genomic deletions. The outbreak affected 2,040 patients, with a fatality rate of 0.5%. Most (83.0%) isolates were multidrug resistant (MDR). The isolates belonged to MLST ST1 and a new variant of the haplotype, H58B. Most isolates contained a chromosomally translocated region containing seven antimicrobial resistance genes, catA1, blaTEM-1, dfrA7, sul1, sul2, strA, and strB, and fragments of the incompatibility group Q1 (IncQ1) plasmid replicon, the class 1 integron, and the mer operon. The genomic analysis revealed 415 SNP differences overall and 35 deletions among 33 of the isolates subjected to whole-genome sequencing. In comparison with other genomes of H58, the Zambian isolates separated from genomes from Central Africa and India by 34 and 52 SNPs, respectively. The phylogenetic analysis indicates that 32 of the 33 isolates sequenced belonged to a tight clonal group distinct from other H58 genomes included in the study. The small numbers of SNPs identified within this group are consistent with the short-term transmission that can be expected over a period of 2 years. The phylogenetic analysis and deletions suggest that a single MDR clone was responsible for the outbreak, during which occasional other S. Typhi lineages, including sensitive ones, continued to cocirculate. The common view is that the emerging global S. Typhi haplotype, H58B, containing the MDR IncHI1 plasmid is responsible for the majority of typhoid infections in Asia and sub-Saharan Africa; we found that a new variant of the haplotype harboring a chromosomally translocated region containing the MDR islands of IncHI1 plasmid has emerged in Zambia. This could change the perception of the term "classical MDR typhoid" currently being solely associated with the IncHI1 plasmid. It might be more common than presently thought that S. Typhi haplotype H58B harbors the IncHI1 plasmid or a chromosomally translocated MDR region or both.
WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and European Union Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark rshe@food.dtu.dk.
Rene S
RS
Hendriksen
WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and European Union Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
Pimlapas
P
Leekitcharoenphon
WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and European Union Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
Oksana
O
Lukjancenko
Department of Pathology and Microbiology, University Teaching Hospital, Lusaka, Zambia.
Chileshe
C
Lukwesa-Musyani
Department of Public Health, Zambia Ministry of Health, Lusaka, Zambia.
Bushimbwa
B
Tambatamba
Department of Pathology and Microbiology, University Teaching Hospital, Lusaka, Zambia.
John
J
Mwaba
Department of Biomedical Sciences, School of Medicine, University of Zambia, Lusaka, Zambia.
Annie
A
Kalonda
Department of Pathology and Microbiology, University Teaching Hospital, Lusaka, Zambia.
Ruth
R
Nakazwe
Department of Biomedical Sciences, School of Medicine, University of Zambia, Lusaka, Zambia.
Geoffrey
G
Kwenda
WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and European Union Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
Jacob Dyring
JD
Jensen
WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and European Union Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
Christina A
CA
Svendsen
WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and European Union Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
Karen K
KK
Dittmann
WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and European Union Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
Rolf S
RS
Kaas
WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and European Union Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
Lina M
LM
Cavaco
WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and European Union Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
Frank M
FM
Aarestrup
WHO Collaborating Centre for Antimicrobial Resistance in Foodborne Pathogens and European Union Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
Henrik
H
Hasman
Department of Pathology and Microbiology, University Teaching Hospital, Lusaka, Zambia.
James C L
JC
Mwansa
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D002876:Chromosomes, Bacterial; D003227:Conjugation, Genetic; D004196:Disease Outbreaks; D024901:Drug Resistance, Multiple, Bacterial; D019143:Evolution, Molecular; D005260:Female; D023061:Gene Order; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D023281:Genomics; D006239:Haplotypes; D049674:History, 21st Century; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D058885:Multilocus Sequence Typing; D009154:Mutation; D010802:Phylogeny; D010957:Plasmids; D020641:Polymorphism, Single Nucleotide; D012485:Salmonella typhi / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D017384:Sequence Deletion; D014178:Translocation, Genetic; D014435:Typhoid Fever / Q000453:epidemiology* / Q000266:history / Q000382:microbiology*; D015024:Zambia / Q000453:epidemiology
D000900:Anti-Bacterial Agents