Molecular Analysis of incHI1 Antimicrobial Resistance Plasmids from Salmonella Serovar Typhi Strains Associated with Typhoid Fever

Abstract

The first outbreak of multidrug-resistant (MDR) typhoid fever in Vietnam was in 1993, and by 1995 nearly 90% of cases were MDR. Plasmid HCM1, sequenced in full, is an incHI1 plasmid from Salmonella enterica serovar Typhi strain CT18, isolated in Vietnam in 1993. Restriction analysis shows that pHCM1 shares a restriction fragment length polymorphism (RFLP) pattern with plasmids isolated from the first outbreak and 10 of 17 MDR plasmids isolated from sporadic cases occurring at the same time in Vietnam. A core region of pHCM1 has significant DNA sequence similarity to plasmid R27, isolated in 1961 from S. enterica in the United Kingdom. There are five regions of DNA in pHCM1 which are not present in R27. Two of these are putative acquisition regions; the largest is 34.955 kbp in length and includes sequences of several antibiotic resistance genes and several insertion sequences. The borders of this region are defined by two identical IS10 left elements, associated with an inversion of DNA or with a truncated Tn10 element. The second, smaller region is 14.751 kbp and carries a trimethoprim resistance gene dfr14A cassette associated with a class 1 integrase. In 1993 to 1994, restriction analysis revealed some variations in the structures of Salmonella serovar Typhi MDR plasmids which were mapped to the two putative acquisition regions and three smaller variable regions. In 1996 a single RFLP type, RFLP7, was found to carry the dfrA7 and sul-1 genes, which were not present on R27 or pHCM1. This plasmid type appears to have a selective advantage over other plasmids with the same resistance phenotype.

Multidrug-ResistantSalmonella entericaSerovar Paratyphi A Harbors IncHI1 Plasmids Similar to Those Found in Serovar Typhi

“…1a and 3, J). Results from PCR assays designed to detect genes in the intI1 variable gene cassette were previously reported by Wain et al (43) (Fig. 3, E and F).…”

“…1. PCR amplicons E and F are PCR results for the detection of dfrA7 and sul1, reported in Wain et al (43), which are present in the variable integron gene cassette (Fig. 2c) in pAKU_1 but not in pHCM1; G targets one end of the insertion of bla/sul/str into Tn21; H and I target the boundaries of the insertion of Tn21 into Tn9, and J targets the insertion site of Tn9 into the IncHI1 backbone.…”

Characterization of Multidrug-Resistant Typhoid Outbreaks in Kenya

“…In addition, there will be a need to ensure that cheaper generic drugs available in the market for the treatment of typhoid are of good quality and are used rationally. As in MDR serovar Typhi outbreaks reported from many parts of the world (16,17,30), multidrug resistance in Kenyan serovar Typhi (which is resistant to five commonly available antimicrobial agents) was encoded on large self-transferable IncHI1 plasmids of ϳ110 kb. It is likely that resistance was acquired through the horizontal transfer of plasmids to previously sensitive strains irrespective of susceptibility to the quinolones commonly in use in Kenya: nalidixic acid, norfloxacin, and ciprofloxacin.…”

A Second Large Plasmid Encodes Conjugative Transfer and Antimicrobial Resistance in O119:H2 and Some Typical O111 Enteropathogenic Escherichia coli Strains

“…If the latter is the case, the question of how the resistance plasmid spread rapidly and apparently selectively within the O111: H2/NM and O119:H2 EPEC lineages arises. Epidemic spread of resistance plasmids within a pathotype has been documented for successful incH plasmids among Salmonella serovar Typhi isolates in Asia (40). The ability of the resistance plasmid to occasionally mobilize the EAF plasmid means that it can, at least in theory, play some role in pathogen evolution.…”