PDF(Pubmed)
Abstract：
The two species that account for most cases of Acinetobacter-associated bacteremia in the United Kingdom are Acinetobacter lwoffii, often a commensal but also an emerging pathogen, and Acinetobacter baumannii, a well-known antibiotic-resistant species. While these species both cause similar types of human infection and occupy the same niche, A. lwoffii (unlike A. baumannii) has thus far remained susceptible to antibiotics. Comparatively little is known about the biology of A. lwoffii, and this is the largest study on it conducted to date, providing valuable insights into its behaviour and potential threat to human health. This study aimed to explain the antibiotic susceptibility, virulence, and fundamental biological differences between these two species. The relative susceptibility of A. lwoffii was explained as it encoded fewer antibiotic resistance and efflux pump genes than A. baumannii (9 and 30, respectively). While both species had markers of horizontal gene transfer, A. lwoffii encoded more DNA defense systems and harbored a far more restricted range of plasmids. Furthermore, A. lwoffii displayed a reduced ability to select for antibiotic resistance mutations, form biofilm, and infect both in vivo and in in vitro models of infection. This study suggests that the emerging pathogen A. lwoffii has remained susceptible to antibiotics because mechanisms exist to make it highly selective about the DNA it acquires, and we hypothesize that the fact that it only harbors a single RND system restricts the ability to select for resistance mutations. This provides valuable insights into how development of resistance can be constrained in Gram-negative bacteria.
OBJECTIVE: Acinetobacter lwoffii is often a harmless commensal but is also an emerging pathogen and is the most common cause of Acinetobacter-derived bloodstream infections in England and Wales. In contrast to the well-studied and often highly drug-resistant A. baumannii, A. lwoffii has remained susceptible to antibiotics. This study explains why this organism has not evolved resistance to antibiotics. These new insights are important to understand why and how some species develop antibiotic resistance, while others do not, and could inform future novel treatment strategies.
OBJECTIVE: Acinetobacter lwoffii is often a harmless commensal but is also an emerging pathogen and is the most common cause of Acinetobacter-derived bloodstream infections in England and Wales. In contrast to the well-studied and often highly drug-resistant A. baumannii, A. lwoffii has remained susceptible to antibiotics. This study explains why this organism has not evolved resistance to antibiotics. These new insights are important to understand why and how some species develop antibiotic resistance, while others do not, and could inform future novel treatment strategies.
摘要：
在英国，占不动杆菌相关菌血症大多数病例的两个物种是不动杆菌，通常是共生的，但也是新兴的病原体，鲍曼不动杆菌,一种众所周知的抗生素抗性物种。虽然这些物种都引起相似类型的人类感染并占据相同的生态位，Lwoffii(不同于鲍曼不动杆菌)迄今仍然对抗生素敏感。相对而言，对A.lwoffii的生物学知之甚少，这是迄今为止对它进行的最大的研究，为其行为和对人类健康的潜在威胁提供有价值的见解。这项研究旨在解释抗生素的敏感性，毒力,以及这两个物种之间的基本生物学差异。lwoffii的相对易感性被解释为它比鲍曼不动杆菌编码更少的抗生素抗性和外排泵基因(分别为9和30)。虽然这两个物种都有水平基因转移的标记，A.lwoffii编码更多的DNA防御系统，并拥有更多有限范围的质粒。此外，A.lwoffii显示选择抗生素抗性突变的能力降低，形成生物膜，并感染体内和体外感染模型。这项研究表明，新兴的病原体A.lwoffii仍然对抗生素敏感，因为存在使其对其获得的DNA具有高度选择性的机制，我们假设它仅包含单个RND系统的事实限制了选择抗性突变的能力。这提供了有关如何在革兰氏阴性细菌中限制抗性发展的有价值的见解。
目的：不动杆菌通常是一种无害的共生菌，但也是一种新兴的病原体，是英格兰和威尔士不动杆菌血流感染的最常见原因。与经过充分研究且通常具有高度耐药性的鲍曼不动杆菌相反，A.lwoffii仍然对抗生素敏感。这项研究解释了为什么这种生物没有对抗生素产生耐药性。这些新见解对于理解某些物种为什么以及如何产生抗生素抗性非常重要，而其他人没有，并可以为未来的新治疗策略提供信息。
目的：不动杆菌通常是一种无害的共生菌，但也是一种新兴的病原体，是英格兰和威尔士不动杆菌血流感染的最常见原因。与经过充分研究且通常具有高度耐药性的鲍曼不动杆菌相反，A.lwoffii仍然对抗生素敏感。这项研究解释了为什么这种生物没有对抗生素产生耐药性。这些新见解对于理解某些物种为什么以及如何产生抗生素抗性非常重要，而其他人没有，并可以为未来的新治疗策略提供信息。
