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

伤寒疫苗接种已经确立，目前正在作为这一主要人类疾病的控制措施加以实施。副伤寒是一种难以区分的疾病，但这种疫苗不包括副伤寒，副伤寒有取代伤寒的危险。这是特别令人担忧的，因为细菌引起的甲型副伤寒沙门氏菌已经对除一种可用的治疗抗生素外的所有抗生素都具有耐药性，包括氟喹诺酮类药物，如环丙沙星。来自印度和远东的几份报告描述了对主要治疗药物环丙沙星有耐药性的副伤寒病例。我们建议详细检查在s副伤寒A耐环丙沙星的发展，因为它出现。这一信息将提高临床从业人员对耐药菌株的认识，从而使患者得到适当治疗，并加强我们对病原菌获得抗生素耐药性的基本过程的理解。对抗生素的耐药性是对现代医学的主要威胁，而且由于甲型副伤寒沙门氏菌的分离株非常相似；在测序的两个分离株中，只有5个基因不同。因此，副伤寒沙门氏菌耐药性的发展为研究细菌耐药性的演变提供了一个理想的机会。通过在实验室菌株中重建自然突变，我们希望观察每种突变对适应度和抗性表型的影响。

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.