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

甲型副伤寒肠沙门氏菌对氟喹诺酮类药物耐药的分子基础和生物学成本。

• 批准号: G0600805/2
• 负责人: John Wain
• 金额: $ 73.67万
• 依托单位: Public Health England
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600805%2F2
• 关键词: molecular; basis; biological; cost; fluoroquinolone

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.

预防伤寒的疫苗接种已经确立，目前正在实施，作为这一主要人类疾病的控制措施。副伤寒是一种难以区分的疾病，但这种疫苗不包括副伤寒，副伤寒有可能取代伤寒。这是特别令人关注的，因为细菌原因，甲型副伤寒沙门氏菌，已成为耐药的所有，但一种可用于治疗的抗生素，包括氟喹诺酮类，如环丙沙星。来自印度和远东的几份报告描述了副伤寒对主要治疗药物环丙沙星耐药的病例。我们建议详细研究环丙沙星耐药性的发展。甲型副伤寒出现时。这些信息将提高临床医生对耐药菌株的认识，从而使患者得到适当的治疗，并提高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现代医学的一个主要威胁，因为S。甲型副伤寒非常相似，测序的两个分离株之间只有5个基因不同。S.因此，甲型副伤寒为研究细菌耐药性的演变提供了一个理想的机会。通过在实验室的S.我们希望观察每种突变对适应性和耐药表型的影响。