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

针对伤寒的疫苗接种已经确立，现在正在实施，作为对这一重大人类疾病的控制措施。然而，副伤寒是一种难以区分的疾病，不在该疫苗的覆盖范围内，存在副伤寒可能取代伤寒的危险。这一点特别令人担忧，因为细菌原因甲型副伤寒沙门氏菌已经对除一种外的所有可治疗抗生素产生抗药性，包括环丙沙星等氟喹诺酮类药物。来自印度和远东的几份报告描述了对环丙沙星耐药的副伤寒病例，环丙沙星是治疗的主要药物。我们建议详细研究甲型副伤寒沙门氏菌对环丙沙星的耐药性。这些信息将提高临床医生对耐药菌株的认识，从而使患者能够得到适当的治疗，并增强我们对病原菌获得抗生素耐药性的基本过程的了解。对抗生素的抗药性是现代医学的一个主要威胁，因为甲型副伤寒沙门氏菌的分离株非常相似；测序的两个分离株中只有五个基因不同。因此，甲型副伤寒沙门氏菌耐药性的发展为研究细菌耐药性的进化提供了一个理想的机会。通过重建甲型副伤寒沙门氏菌实验室菌株的自然突变，我们希望观察每个突变对适应度的影响以及对耐药性表型的影响。

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.