Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA
Department of Large Animal Medicine, University of Georgia, Athens, Georgia, USA.
Appl Environ Microbiol. 2019 Mar 22;85(7). doi: 10.1128/AEM.02665-18. Print 2019 Apr 1.
is a leading cause of severe pneumonia in foals. Standard treatment is dual antimicrobial therapy with a macrolide and rifampin, but the emergence of macrolide- and rifampin-resistant isolates is an increasing problem. The objective of this study was to determine the effect of macrolide and/or rifampin resistance on fitness of Three unique isogenic sets were created, each consisting of four strains, as follows: a susceptible parent isolate, strains resistant to macrolides or rifampin, and a dual macrolide- and rifampin-resistant strain. Each isogenic set's bacterial growth curve was generated in enriched medium, minimal medium (MM), and minimal medium without iron (MM-I). Bacterial survival in soil was analyzed over 12 months at -20°C, 4°C, 25°C, and 37°C, and the ability of these strains to retain antimicrobial resistance during sequential subculturing was determined. Insertion of the mobile element conferring macrolide resistance had minimal effect on growth. However, two of three mutations conferring rifampin resistance resulted in a decreased growth rate in MM. In soil, macrolide- or rifampin-resistant strains exhibited limited growth compared to that of the susceptible isolate at all temperatures except -20°C. During subculturing, macrolide resistance was lost over time, and two of three mutations reverted to the wild-type form. The growth of rifampin-resistant colonies is delayed under nutrient restriction. In soil, possession of rifampin or macrolide resistance results in decreased fitness. Both macrolide and rifampin resistance can be lost after repeated subculturing. This work advances our understanding of the opportunistic environmental pathogen , a disease agent affecting horses and immunocompromised people. is one of the most common causes of severe pneumonia in young horses. For decades, the standard treatment for pneumonia in horses has been dual antimicrobial therapy with a macrolide and rifampin; effective alternatives to this combination are lacking. The World Health Organization classifies these antimicrobial agents as critically important for human medicine. Widespread macrolide and rifampin resistance in isolates is a major emerging problem for the horse-breeding industry and might also adversely impact human health if resistant strains infect people or transfer resistance mechanisms to other pathogens. This study details the impact of antimicrobial resistance on fitness, a vital step for understanding the ecology and epidemiology of resistant isolates, and will support development of novel strategies to combat antimicrobial resistance.
是幼驹严重肺炎的主要病因。标准治疗是大环内酯类和利福平的双重抗菌疗法，但大环内酯类和利福平耐药分离株的出现是一个日益严重的问题。本研究的目的是确定大环内酯类和/或利福平耐药性对三种独特的同基因系的影响，每个同基因系由以下四个菌株组成：敏感亲本分离株、对大环内酯类或利福平耐药的菌株以及对大环内酯类和利福平耐药的双重菌株。在富集培养基、最低培养基 (MM) 和不含铁的最低培养基 (MM-I) 中生成每个同基因系的细菌生长曲线。在-20°C、4°C、25°C 和 37°C 下分析土壤中细菌 12 个月的存活情况，并确定这些菌株在连续传代过程中保留抗菌耐药性的能力。携带赋予大环内酯类耐药性的可移动元件的插入对生长的影响最小。然而，三种赋予利福平耐药性的突变中的两种导致 MM 中的生长速度降低。在土壤中，与敏感分离株相比，除-20°C 外，所有温度下大环内酯类或利福平耐药的 菌株的生长均受到限制。在传代过程中，大环内酯类耐药性随时间丧失，三种突变中的两种恢复为野生型。在营养限制下，利福平耐药菌的生长会延迟。在土壤中，携带利福平或大环内酯类耐药性会降低适应性。重复传代后，大环内酯类和利福平耐药性都可能丧失。这项工作增进了我们对机会性病原体 的理解，该病原体是一种影响马和免疫功能低下人群的疾病因子。是幼驹严重肺炎的最常见原因之一。几十年来，马肺炎的标准治疗方法是大环内酯类和利福平的双重抗菌疗法；这种组合的有效替代品缺乏。世界卫生组织将这些抗菌剂列为对人类医学至关重要的药物。广泛存在的大环内酯类和利福平耐药性是马养殖业的一个主要新兴问题，如果耐药菌株感染人类或向其他病原体转移耐药机制，也可能对人类健康产生不利影响。本研究详细说明了抗菌耐药性对 适应性的影响，这是了解耐药分离株的生态学和流行病学的重要一步，并将支持制定新的策略来对抗抗菌耐药性。
