Isolation and characterization of lytic phage TUN1 specific for Klebsiella pneumoniae K64 clinical isolates from Tunisia.

Isolation and characterization of lytic phage TUN1 specific for Klebsiella pneumoniae K64 clinical isolates from Tunisia.
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DOI:
10.1186/s12866-021-02251-w
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发表时间:
2021-06-21
期刊:
影响因子:
4.2
通讯作者:
Bugert JJ
Bugert JJ
中科院分区:
生物学3区
文献类型:
--
作者:
Eckstein S;Stender J;Mzoughi S;Vogele K;Kühn J;Friese D;Bugert C;Handrick S;Ferjani M;Wölfel R;Millard A;Ben Moussa M;Bugert JJ

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多重耐药肺炎克雷伯菌(kp)是呼吸道、尿路和伤口严重感染的新兴病原体,可发展为致命败血症。噬菌体的使用目前被认为是抗生素治疗的有效替代或辅助。在这项研究中,我们通过Kp wzi基因的部分扩增和测序,报告了2014-2018年在突尼斯军事医院(MHT)分离的163例碳青霉烯类耐药Kp(CRKP)的胶囊(K)分型。总体上最常见的K型是K64,占50.3%,其次是K17和K27(分别为22.7%和11.0%)。K64 Kp菌株是最常见的,并且与增加的病例/死亡率相关,特别是在重症监护室(ICU)。使用K64 Kp菌株,我们从MHT的ICU废水样品中分离并表征了裂解性Kp噬菌体vB_KpP_TUN1(噬菌体TUN 1)。TUN 1属于Autographiviridae家族,并且最可能通过由gp 47编码的解聚酶特异性地破坏K64 Kp胶囊。此外,我们成功地在非复制型宿主(E. coli),提高了在没有活细菌宿主的情况下体外组装的可能性。我们认为噬菌体TU 1是一种很有前途的候选物,可用作CRKP感染中抗生素治疗的佐剂或替代品,促进噬菌体治疗的监管批准。K64、K17和K27是北方非洲这一地理位置上最常见的wzi胶囊类型。裂解噬菌体TU 1有效地裂解与体温下增加的病例/死亡率相关的K64 Kp菌株。连同其在非复制宿主中被拯救的能力,这些特征增强了该噬菌体作为抗菌剂的效用。在线版本包含补充材料,可通过10.1186/s12866-021-02251-w获得。
Multidrug-resistant Klebsiella pneumoniae spp. (kp) are emerging agents of severe infections of the respiratory, urinary tract and wounds that can progress to fatal septicemia. The use of bacteriophages is currently being considered as an effective alternative or adjuvant to antibiotic therapy. In this study, we report capsule (K)-typing of 163 carbapenem-resistant Kp (CRKP) isolated 2014–2018 at the Military Hospital of Instruction of Tunis (MHT), Tunisia, by partial amplification and sequencing of the Kp wzi gene. The most prevalent K-type overall was K64 with 50.3% followed by K17 and K27 (22.7 and 11.0%, respectively). K64 Kp strains were most common and associated with increased case/fatality rates, especially at the intensive care unit (ICU). Using a K64 Kp strain we isolated and characterized a lytic Kp phage, vB_KpP_TUN1 (phage TUN1), from wastewater samples of the ICU at the MHT. TUN1 belongs to the Autographiviridae family and specifically digests K64 Kp capsules most probably via a depolymerase encoded by gp47. Furthermore, we successfully assembled phage TUN1 in a non-replicative host (E. coli) raising the possibility of in vitro assembly in the absence of live bacterial hosts. We propose that phage TUN1 is a promising candidate to be used as an adjuvant or an alternative to antibiotic therapy in CRKP infections, facilitating regulatory approval of phage therapy. K64, K17 and K27 are the most common wzi capsule types in this geographical location in Northern Africa. The lytic phage TUN1 efficiently lyses K64 Kp strains associated with increased case/fatality rates at body temperature. Together with its ability to be rescued in a non-replicative host these features enhance the utility of this phage as an antibacterial agent. The online version contains supplementary material available at 10.1186/s12866-021-02251-w.
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