Wottrich Stephanie, Mendonca Stacee, Safarpour Cameron, Nguyen Christine, Marinelli Laura J, Hancock Stephen P, Modlin Robert L, Parker Jordan Moberg
Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90024, USA.
Department of Neurology, Dell Seton Medical Center at the University of Texas at Austin, Austin, TX 78701, USA.
Microbiome Res Rep. 2024 Apr 18;3(3):27. doi: 10.20517/mrr.2023.42. eCollection 2024.
, formerly , is a bacterial species characterized by tenacious acne-contributing pathogenic strains. Therefore, bacteriophage therapy has become an attractive treatment route to circumvent issues such as evolved bacterial antibiotic resistance. However, medical and commercial use of phage therapy for has been elusive, necessitating ongoing exploration of phage characteristics that confer bactericidal capacity. A novel phage (Aquarius) was isolated and analyzed. Testing included genomic sequencing and annotation, electron microscopy, patch testing, reinfection assays, and qPCR to confirm pseudolysogeny and putative superinfection exclusion (SIE) protein expression. Given a superinfection-resistant phenotype was observed, reinfection assays and patch tests were performed, which confirmed the re-cultured bacteria were resistant to superinfection. Subsequent qPCR indicated pseudolysogeny was a concomitantly present phenomenon. Phage genomic analysis identified the presence of a conserved gene () with a product containing Ltp family-like protein signatures which may contribute to phage-mediated bacterial superinfection resistance (SIR) in a pseudolysogeny-dependent manner. qPCR was performed to analyze and roughly quantify gp41 activity, and mRNA expression was high during infection, implicating a role for the protein during the phage life cycle. This study confirms that bacteria are capable of harboring phage pseudolysogens and suggests that this phenomenon plays a role in bacterial SIR. This mechanism may be conferred by the expression of phage proteins while the phage persists within the host in the pseudolysogenic state. This parameter must be considered in future endeavors for efficacious application of phage-based therapeutics.
以前称为 ，是一种具有顽固的导致痤疮的致病菌株的细菌物种。因此，噬菌体疗法已成为一种有吸引力的治疗途径，以规避诸如细菌抗生素耐药性进化等问题。然而，噬菌体疗法在医学和商业上对 的应用一直难以实现，因此有必要持续探索赋予杀菌能力的噬菌体特性。分离并分析了一种新型噬菌体（水瓶座）。测试包括基因组测序和注释、电子显微镜、斑贴试验、再感染试验以及定量聚合酶链反应（qPCR），以确认假溶原性和假定的超感染排除（SIE）蛋白表达。鉴于观察到超感染抗性表型，进行了再感染试验和斑贴试验，证实重新培养的细菌对超感染具有抗性。随后的qPCR表明假溶原性是一种伴随出现的现象。噬菌体基因组分析确定存在一个保守基因（），其产物含有类似Ltp家族的蛋白特征，这可能以假溶原性依赖的方式促进噬菌体介导的细菌超感染抗性（SIR）。进行qPCR以分析并大致定量gp41活性，并且在感染期间mRNA表达很高，这表明该蛋白在噬菌体生命周期中起作用。本研究证实 细菌能够携带噬菌体假溶原菌，并表明这种现象在细菌SIR中起作用。这种机制可能是由噬菌体蛋白的表达赋予的，而噬菌体以假溶原状态存在于宿主内。在未来有效应用基于 的噬菌体疗法的努力中必须考虑这个参数。
