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一剂烈性噬菌体能拯救感染多重耐药铜绿假单胞菌的菌血症小鼠。

A single dose of a virulent bacteriophage vB PaeP-SaPL, rescues bacteremic mice infected with multi drug resistant Pseudomonas aeruginosa.

机构信息

Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore 54590, Pakistan; Department of Microbiology, Hazara University, Mansehra 21300, Pakistan.

Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore 54590, Pakistan.

出版信息

Virus Res. 2021 Jan 15;292:198250. doi: 10.1016/j.virusres.2020.198250. Epub 2020 Nov 28.

Abstract

Multidrug resistant bacterial infections are difficult to treat and contribute to high morbidity and mortality. The phage vB PaeP-SaPL was isolated from a sewage drain (Lahore, Pakistan) against Pseudomonas aeruginosa PA-1 (NCBI Accession number MG763232). SaPL produced circular, transparent plaques, 4-5 mm in diameter and showed broad host range infecting 57 % of tested MDR P. aeruginosa clinical isolates (N = 38), while no infectivity was observed against any tested strains of other genera. SaPL inhibited PA-1 growth until 24 h post infection at MOI of 1. The SaPL showed stability at varying temperature and pH, with optimum stability at pH 7 and 45 °C. The latent period of SaPL was 20 min with burst size of 155 virions. The genome of SaPL was double stranded DNA of 45,796 bps having 63 CDS (13 for known proteins and 50 for hypothetical proteins) with a GC content of 52 %. The termini analysis revealed that SaPL genome ends are redundant and permuted. The packaging strategy used by SaPL was a headful (pac) strategy like P1 phage. Survivability of PA-1 challenged mice, treated with SaPL (100 %) was statistically significant (P < 0.05) than in untreated challenged mice (0%). Based on its efficacy in reducing bacterial growth, selective infectivity against majority of P. aeruginosa strains and its ability to increase survivability in PA-1 challenged mice, SaPL is proposed to be a potential candidate for bacteriophage therapy against difficult to treat MDR P. aeruginosa infections.

摘要

耐多药细菌感染难以治疗,导致高发病率和死亡率。噬菌体 vB PaeP-SaPL 是从污水渠(巴基斯坦拉合尔)中分离出来的,针对的是铜绿假单胞菌 PA-1(NCBI 注册号 MG763232)。SaPL 产生圆形、透明的噬菌斑,直径 4-5 毫米,表现出广泛的宿主范围,感染了 57%的测试的耐多药铜绿假单胞菌临床分离株(N = 38),而对任何测试的其他属的菌株都没有观察到感染性。SaPL 在感染复数为 1 时,在 24 小时内抑制 PA-1 的生长。SaPL 在不同的温度和 pH 值下表现出稳定性,在 pH 7 和 45°C 时稳定性最佳。SaPL 的潜伏期为 20 分钟,爆发量为 155 个病毒粒子。SaPL 的基因组是 45796 bps 的双链 DNA,有 63 个 CDS(13 个为已知蛋白,50 个为假设蛋白),GC 含量为 52%。末端分析表明,SaPL 基因组的末端是冗余和易位的。SaPL 使用的包装策略是类似于 P1 噬菌体的从头(pac)策略。用 SaPL(100%)治疗的 PA-1 感染小鼠的存活率在统计学上显著(P < 0.05)高于未治疗的感染小鼠(0%)。基于其减少细菌生长的功效、对大多数铜绿假单胞菌菌株的选择性感染性以及在 PA-1 感染小鼠中提高存活率的能力,SaPL 被提议作为治疗难以治疗的耐多药铜绿假单胞菌感染的噬菌体治疗的潜在候选物。

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