MOA Key Laboratory of Food Safety Evaluation, National Reference Laboratory of Veterinary Drug Residue (HZAU), Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
Microb Pathog. 2011 Jun;50(6):336-42. doi: 10.1016/j.micpath.2011.02.009. Epub 2011 Mar 4.
Epidemiological studies of macrolide resistance in Campylobacter jejuni demonstrated that infections with macrolide-resistant C. jejuni could be associated with an increased risk of adverse events, development of invasive illness or death compared to macrolide-susceptible isolates. In this study, an in vitro induction experiment was conducted using susceptible C. jejuni strain and erythromycin as a selecting agent to obtain Ery-resistant mutant with 23S rRNA gene mutation (A2074C). Changes in the virulence characteristics and fitness between the susceptible parent strain and Ery-resistant mutant were examined. Ery-resistant mutant demonstrated slightly more resistance to bile in the bile tolerance assay compared to the susceptible strain but with no statistical significant difference. However Ery-resistant mutant apparently demonstrated reduced adhesion and invasion characteristics to intestinal epithelial cells, murine macrophage and short time intracellular survivability within macrophage compared to the susceptible strain. Co-inoculation of the two strains in the mice resulted in low colonization level of the resistant strain compared to the susceptible strain. Competition experiments resulted in mutant that grew significantly slower than the susceptible parent strain and the mutation imposed a fitness cost in Ery-resistant mutant. Taken together these findings demonstrated the increment of the virulence characteristics of Ery-susceptible strain rather than Ery-resistant strain. The adverse events previously observed in the epidemiological studies for macrolide-resistant strains infection, we suggested this maybe attributed to the resistivity of the resistant strains to the treatment and consequently prolonged the symptoms and compromised the disease in patients.
对空肠弯曲菌大环内酯类耐药性的流行病学研究表明，与大环内酯类敏感分离株相比，感染大环内酯类耐药性空肠弯曲菌与不良事件风险增加、侵袭性疾病或死亡相关。在这项研究中，使用敏感的空肠弯曲菌菌株和红霉素作为选择剂进行体外诱导实验，获得具有 23S rRNA 基因突变（A2074C）的红霉素耐药突变体。研究了敏感亲本菌株和红霉素耐药突变体之间的毒力特征和适应性变化。与敏感株相比，胆汁耐受试验中红霉素耐药突变体对胆汁的耐药性略有增加，但无统计学差异。然而，与敏感株相比，红霉素耐药突变体明显表现出对肠上皮细胞、鼠巨噬细胞的黏附和侵袭特性降低，以及在巨噬细胞内的短时间内生存能力降低。两种菌株在小鼠中的共同接种导致耐药菌株的定植水平低于敏感菌株。竞争实验导致突变体的生长速度明显低于敏感亲本菌株，并且突变给红霉素耐药突变体带来了适应性成本。总之，这些发现表明，红霉素敏感株的毒力特征增加，而不是红霉素耐药株。以前在流行病学研究中观察到的大环内酯类耐药株感染的不良事件，我们认为这可能归因于耐药株对治疗的抵抗力，从而延长了症状并使患者的病情恶化。
