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

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Vaccination against typhoid fever is well established and is now being implemented as a control measure for this major human disease. Paratyphoid fever, an indistinguishable disease, however is not covered by this vaccine and there is a danger that paratyphoid may replace typhoid fever. This is of particular concern because the bacterial cause, Salmonella Paratyphi A, has become resistant to all but one of the antibiotics available for treatment, including fluoroquinolones such as ciprofloxacin. Several reports from India and the Far East describe cases of paratyphoid fever resistant to ciprofloxacin, the main drug for treatment. We propose to examine in detail the development of resistance to ciprofloxacin in S. Paratyphi A as it emerges. This information will increase awareness among clinical practitioners about resistant strains and so allow patients to be treated appropriately and enhance our understanding of the fundamental process of acquisition of antibiotic resistance in pathogenic bacteria. Resistance to antibiotics is a major threat to modern medicine, and because isolates of S. Paratyphi A are very similar; only five genes differ between the two isolates sequenced. The development of resistance in S. Paratyphi A therfore provides an ideal opportunity to study the evolution of resistance in bacteria. By recreating the natural mutations in laboratory strains of S. Paratyphi A we hope to observe the effects of each mutation on fitness as well on the resistance phenotype.