Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia.
The Department of Surgery - Otolaryngology Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide, South Australia, Australia.
Microb Genom. 2021 Dec;7(12). doi: 10.1099/mgen.0.000726.
Prophages affect bacterial fitness on multiple levels. These include bacterial infectivity, toxin secretion, virulence regulation, surface modification, immune stimulation and evasion and microbiome competition. Lysogenic conversion arms bacteria with novel accessory functions thereby increasing bacterial fitness, host adaptation and persistence, and antibiotic resistance. These properties allow the bacteria to occupy a niche long term and can contribute to chronic infections and inflammation such as chronic rhinosinusitis (CRS). In this study, we aimed to identify and characterize prophages present in from patients suffering from CRS in relation to CRS disease phenotype and severity. Prophage regions were identified using PHASTER. Various tools like ResFinder and VF Analyzer were used to detect virulence genes and antibiotic resistance genes respectively. Progressive MAUVE and maximum likelihood were used for multiple sequence alignment and phylogenetics of prophages respectively. Disease severity of CRS patients was measured using computed tomography Lund-Mackay scores. Fifty-eight clinical isolates (CIs) were obtained from 28 CRS patients without nasal polyp (CRSsNP) and 30 CRS patients with nasal polyp (CRSwNP). All CIs carried at least one prophage (average=3.6) and prophages contributed up to 7.7 % of the bacterial genome. Phage integrase genes were found in 55/58 (95 %) strains and 97/211 (46 %) prophages. Prophages belonging to Sa3int integrase group (phiNM3, JS01, phiN315) (39/97, 40%) and Sa2int (phi2958PVL) (14/97, 14%) were the most prevalent prophages and harboured multiple virulence genes such as E/D, . Intact prophages were more frequently identified in CRSwNP than in CRSsNP (=0.0021). Intact prophages belonging to the Sa3int group were more frequent in CRSwNP than in CRSsNP (=0.0008) and intact phiNM3 were exclusively found in CRSwNP patients (=0.007). Our results expand the knowledge of prophages in isolated from CRS patients and their possible role in disease development. These findings provide a platform for future investigations into potential tripartite associations between bacteria-prophage-human immune system, evolution and CRS disease pathophysiology.
噬菌体在多个层面上影响细菌的适应性。这些功能包括细菌的感染力、毒素分泌、毒力调控、表面修饰、免疫刺激和逃避以及微生物组竞争。溶原性转换为细菌提供了新的辅助功能，从而提高了细菌的适应性、宿主适应性和持久性，以及抗生素耐药性。这些特性使细菌能够长期占据特定生态位，并可能导致慢性感染和炎症，如慢性鼻-鼻窦炎（CRS）。在这项研究中，我们旨在鉴定和描述来自患有 CRS 的患者的 中存在的噬菌体，并将其与 CRS 疾病表型和严重程度相关联。使用 PHASTER 识别噬菌体区域。使用各种 工具，如 ResFinder 和 VF Analyzer，分别检测毒力基因和抗生素耐药基因。使用渐进式 MAUVE 和最大似然法分别进行噬菌体的多序列比对和系统发育分析。使用计算机断层扫描 Lund-Mackay 评分来衡量 CRS 患者的疾病严重程度。从 28 名无鼻息肉（CRSsNP）和 30 名鼻息肉（CRSwNP）的 CRS 患者中获得了 58 株 临床分离株（CIs）。所有的 CIs 都携带至少一个噬菌体（平均=3.6），噬菌体占细菌基因组的比例高达 7.7%。在 55/58（95%）株和 97/211（46%）噬菌体中发现了噬菌体整合酶基因。属于 Sa3int 整合酶组（phiNM3、JS01、phiN315）（39/97，40%）和 Sa2int（phi2958PVL）（14/97，14%）的噬菌体是最常见的噬菌体，并且携带多种毒力基因，如 E/D、。完整的噬菌体在 CRSwNP 中比在 CRSsNP 中更常被发现（=0.0021）。属于 Sa3int 组的完整噬菌体在 CRSwNP 中比在 CRSsNP 中更为常见（=0.0008），而完整的 phiNM3 仅在 CRSwNP 患者中发现（=0.007）。我们的结果扩展了从 CRS 患者中分离的 噬菌体的知识，及其在疾病发展中的潜在作用。这些发现为进一步研究细菌-噬菌体-人类免疫系统之间的潜在三方关联、细菌进化和 CRS 疾病病理生理学提供了一个平台。
