Department of Pediatrics, Division of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Emory University School of Medicine, Atlanta, Georgia, USA.
Emory+Children's Center for Cystic Fibrosis and Airway Disease Research, Emory University School of Medicine, Atlanta, Georgia, USA.
mSphere. 2024 Jul 30;9(7):e0033524. doi: 10.1128/msphere.00335-24. Epub 2024 Jul 9.
Over 160,000 people worldwide suffer from cystic fibrosis (CF), a genetic condition that causes mucus to accumulate in internal organs. Lung decline is a significant health burden for people with CF (pwCF), and chronic bacterial pulmonary infections are a major cause of death. complex (Smc) is an emerging, multidrug-resistant CF pathogen that can cause pulmonary exacerbations and result in higher mortality. However, little is known about the antagonistic interactions that occur between Smc isolates from pwCF and competitor bacteria. We obtained 13 Smc isolates from adult and pediatric pwCF located in the United States or Australia. We co-cultured these isolates with , and . We also performed whole-genome sequencing of these Smc isolates and compared their genomes using average nucleotide identity analyses. We observed that some Smc CF isolates can engage in antagonistic interactions with and but recovered a substantial number of and cells following co-cultures with all tested Smc isolates. By contrast, we discovered that most Smc CF isolates display strong antibacterial properties against cells and reduce recovery below detectable limits. Finally, we demonstrate that Smc CF strains from this study belong to diverse phylogenetic lineages.
Antagonism toward competitor bacteria may be important for the survival of complex (Smc) in external environments, for the elimination of commensal species and colonization of upper respiratory tracts to enable early infections, and for competition against other pathogens after establishing chronic infections. These intermicrobial interactions could facilitate the acquisition of Smc by people with cystic fibrosis from environmental or nosocomial sources. Elucidating the mechanisms used by Smc to eliminate other bacteria could lead to new insights into the development of novel treatments.
全球有超过 16 万人患有囊性纤维化(CF),这是一种导致粘液在内部器官中积聚的遗传疾病。肺部衰退是 CF 患者(pwCF)的一个重大健康负担,慢性细菌性肺部感染是导致死亡的主要原因。复杂(Smc)是一种新兴的、多药耐药的 CF 病原体,可引起肺部恶化,并导致更高的死亡率。然而,对于 Smc 分离株与竞争细菌之间发生的拮抗相互作用知之甚少。我们从位于美国或澳大利亚的成年和儿科 CF 患者中获得了 13 个 Smc 分离株。我们将这些分离株与 、 和 共培养。我们还对这些 Smc 分离株进行了全基因组测序,并使用平均核苷酸同一性分析比较了它们的基因组。我们观察到一些 Smc CF 分离株可以与 和 发生拮抗相互作用,但在与所有测试的 Smc 分离株共培养后,回收了大量的 和 细胞。相比之下,我们发现大多数 Smc CF 分离株对 细胞表现出强烈的抗菌特性,并将其回收量降低到检测限以下。最后,我们证明了来自本研究的 Smc CF 菌株属于不同的系统发育谱系。
对竞争细菌的拮抗作用可能对 Smc 在外环境中的生存、对共生物种的消除和上呼吸道定植以促进早期感染、以及在建立慢性感染后对抗其他病原体的竞争都很重要。这些微生物间的相互作用可以促进 CF 患者从环境或医院源获得 Smc。阐明 Smc 用于消除其他细菌的机制可以为新的治疗方法的开发提供新的见解。