Variation in Salmonella enterica Serovar Typhi IncHI1 Plasmids during the Global Spread of Resistant Typhoid Fever

Abstract

A global collection of plasmids of the IncHI1 incompatibility group from Salmonella enterica serovar Typhi were analyzed by using a combination of DNA sequencing, DNA sequence analysis, PCR, and microarrays. The IncHI1 resistance plasmids of serovar Typhi display a backbone of conserved gene content and arrangement, within which are embedded preferred acquisition sites for horizontal DNA transfer events. The variable regions appear to be preferred acquisition sites for DNA, most likely through composite transposition, which is presumably driven by the acquisition of resistance genes. Plasmid multilocus sequence typing, a molecular typing method for IncHI1 plasmids, was developed using variation in six conserved loci to trace the spread of these plasmids and to elucidate their evolutionary relationships. The application of this method to a collection of 36 IncHI1 plasmids revealed a chronological clustering of plasmids despite their difference in geographical origins. Our findings suggest that the predominant plasmid types present after 1993 have not evolved directly from the earlier predominant plasmid type but have displaced them. We propose that antibiotic selection acts to maintain resistance genes on the plasmid, but there is also competition between plasmids encoding the same resistance phenotype.

Genomic Signature of Multidrug-Resistant Salmonella enterica Serovar Typhi Isolates Related to a Massive Outbreak in Zambia between 2010 and 2012

“…However, it might be more commonly the case than anticipated that S. Typhi haplotype H58B harbors the IncHI1 plasmid or chromosomally translocated antimicrobial resistance islands or both. It has been hypothesized that a milestone of IncHI1 plasmid evolution had been reached around 1996 by the acquisition of increased fitness, with the result that the IncHI1 plasmid has outcompeted all other plasmid types in S. Typhi (44). However, it has also been argued that plasmid fitness cost must play a role in maintaining IncHI1 plasmids in S. Typhi.…”

Typhoid in Kenya Is Associated with a Dominant Multidrug-Resistant Salmonella enterica Serovar Typhi Haplotype That Is Also Widespread in Southeast Asia

“…The chromosomal haplotypes of S. Typhi isolates were determined based on the SNPs present at 1,485 chromosomal loci identified previously (11,27; see also Table S1 and the methods in the supplemental material). These and eight IncHI1 plasmid loci identified previously (25) were investigated using a GoldenGate custom panel according to the manufacturer's standard protocols (Illumina) (see the methods in the supplemental material). A maximum-likelihood phylogenetic tree based on chromosomal SNPs was constructed using RAxML software (29).…”

“…However, this monophyletic (clonal) pathogen presents particular challenges in this regard. Studies on the population structure of S. Typhi have shown that this human-adapted pathogen exhibits extremely limited genetic variation, challenging our ability to develop discriminatory tools of value in the field (3,11,25,27). However, the application of novel deep-sequencing and bioinformatics approaches has succeeded in stratifying the S. Typhi population into distinct phylogenetic lineages based on over 1,000 single-nucleotide polymorphisms (SNPs) distributed throughout the chromosome.…”

“…For many years, the antibiotics chloramphenicol, ampicillin, and cotrimoxazole formed the mainstays of typhoid treatment. However, outbreaks of multidrug-resistant (MDR) S. Typhi (20,24,25) prompted the widespread use of fluoroquinolones, such as ciprofloxacin and ofloxacin. Fluoroquinolone usage was followed by the emergence of nalidixic acid-resistant S. Typhi exhibiting reduced susceptibility to fluoroquinolones in the early 1990s (18,22), and it has since become widespread (1,12,16,19,25).…”

Scientific Opinion on the public health risks of bacterial strains producing extended-spectrum β-lactamases and/or AmpC β-lactamases in food and food-producing animals

“…(Garcia-Fernandez et al, 2009;Literak et al, 2009;Moodley and Guardabassi, 2009) 2. (Garcia-Fernandez et al, 2008;Phan et al, 2009;Villa et al, 2010) …”