Environmental Pseudomonads Inhibit Cystic Fibrosis Patient-Derived Pseudomonas aeruginosa

Environmental Pseudomonads Inhibit Cystic Fibrosis Patient-Derived Pseudomonas aeruginosa
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DOI:
10.1128/aem.02701-16
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发表时间:
2017-01-01
影响因子:
4.4
通讯作者:
Wildschutte, Hans
Wildschutte, Hans
中科院分区:
生物学2区
文献类型:
--
作者:
Chatterjee, Payel;Davis, Elizabeth;Wildschutte, Hans

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铜绿假单胞菌是一种机会致病菌,它对目前使用的许多抗生素都产生了耐药性。虽然许多研究致力于致病性铜绿假单胞菌在囊性纤维化(CF)患者中的作用,但对其生态特性了解较少。在慢性感染的CF患者中,铜绿假单胞菌占主导地位,但在某些环境中,其丰度低于其他不同的假单胞菌群。在这里,我们试图确定临床分离的铜绿假单胞菌是否容易受到环境假单胞菌的影响,这些假单胞菌在一对一的竞争中主导着土壤和水的栖息地,这可能提供了抑制因子的来源。我们从土壤和淡水生态系统的不同生境中分离出330株假单胞菌,并对这些菌株进行相互竞争,以确定它们的拮抗活性。观察到900多个单独的抑制事件。将分析扩展到铜绿假单胞菌分离株,发现临床分离株,包括藻酸盐产量增加的临床分离株,容易受到多种环境菌株的竞争。我们对一个菌株进行了转座子诱变,发现了一个与14.8kb相似的参与拮抗活性的基因座。只观察到另外两个环境分离株携带该基因,这表明存在其他独特的化合物或参与竞争的其他铜绿假单胞菌之间的相互作用。这一菌株集合代表了对多种致病菌株具有活性的化合物的来源。随着铜绿假单胞菌对当前常用抗生素耐药性的演变,这些环境菌株为临床耐药菌株提供了新的化合物发现的机会。我们观察到许多不同的环境菌株对一组临床分离的铜绿假单胞菌表现出不同的拮抗特性,表明这些生态菌株之间存在不同的抑制机制。了解这些拮抗事件的性质为发现抗菌化合物或代谢途径提供了可能性,这些化合物或代谢途径对于开发治疗铜绿假单胞菌感染的新方法至关重要。
Pseudomonas aeruginosa is an opportunistic pathogen which is evolving resistance to many currently used antibiotics. While much research has been devoted to the roles of pathogenic P. aeruginosa in cystic fibrosis (CF) patients, less is known of its ecological properties. P. aeruginosa dominates the lungs during chronic infection in CF patients, yet its abundance in some environments is less than that of other diverse groups of pseudomonads. Here, we sought to determine if clinical isolates of P. aeruginosa are vulnerable to environmental pseudomonads that dominate soil and water habitats in one-to-one competitions which may provide a source of inhibitory factors. We isolated a total of 330 pseudomonads from diverse habitats of soil and freshwater ecosystems and competed these strains against one another to determine their capacity for antagonistic activity. Over 900 individual inhibitory events were observed. Extending the analysis to P. aeruginosa isolates revealed that clinical isolates, including ones with increased alginate production, were susceptible to competition by multiple environmental strains. We performed transposon mutagenesis on one isolate and identified an similar to 14.8-kb locus involved in antagonistic activity. Only two other environmental isolates were observed to carry the locus, suggesting the presence of additional unique compounds or interactions among other isolates involved in outcompeting P. aeruginosa. This collection of strains represents a source of compounds that are active against multiple pathogenic strains. With the evolution of resistance of P. aeruginosa to currently used antibiotics, these environmental strains provide opportunities for novel compound discovery against drug-resistant clinical strains.IMPORTANCE We demonstrate that clinical CF-derived isolates of P. aeruginosa are susceptible to competition in the presence of environmental pseudomonads. We observed that many diverse environmental strains exhibited varied antagonistic profiles against a panel of clinical P. aeruginosa isolates, suggesting the presence of distinct mechanisms of inhibition among these ecological strains. Understanding the properties of these antagonistic events offers the potential for discoveries of antimicrobial compounds or metabolic pathways important to the development of novel treatments for P. aeruginosa infections.