Potential of training of anti-Staphylococcus aureus therapeutic phages against Staphylococcus epidermidis multidrug-resistant isolates is restricted by inter- and intra-sequence type specificity.

IF 5 2区 生物学 Q1 MICROBIOLOGY mSystems Pub Date : 2024-10-22 Epub Date: 2024-09-09 DOI:10.1128/msystems.00850-24
Camille Kolenda, Mélanie Bonhomme, Mathieu Medina, Mateo Pouilly, Clara Rousseau, Emma Troesch, Patricia Martins-Simoes, Marc Stegger, Paul O Verhoeven, Floriane Laumay, Frédéric Laurent
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Abstract

Phage therapy appears to be a promising approach to tackle multidrug-resistant bacteria, including staphylococci. However, most anti-staphylococcal phages have been characterized in Staphylococcus aureus, while a limited number of studies investigated phage activity against S. epidermidis. We studied the potential of phage training to extend the host range of two types of anti-S. aureus phages against S. epidermidis isolates. The Appelmans protocol was applied to a mixture of Kayvirus and a mixture of Silviavirus phages repeatedly exposed to seven S. epidermidis strains representative of nosocomial-associated sequence types (ST), including the world-wide disseminated ST2. We observed increased activity only for the Kayvirus mixture against two of these strains (ST2 or ST35). Phage subpopulations isolated from the training mixture using these two strains (five/strain) exhibited different evolved phenotypes, active only against their isolation strain or strains of the same ST. Of note, 16/47 ST2 strains were susceptible to one of the groups of trained phages. A comparative genomic analysis of ancestral and trained phage genomes, conducted to identify potential bacterial determinants of such specific activity, found numerous recombination events between two of the three ancestors. However, a small number of trained phage genes had nucleotide sequence modifications impacting the corresponding protein compared to ancestral phages, two to four of them per phage genome being specific of each group of phage subpopulations exhibiting different host range. The results suggest that anti-S. aureus phages can be adapted to S. epidermidis isolates but with inter- and intra-ST specificity.ImportanceS. epidermidis is increasingly recognized as a threat for public health. Its clinical importance is notably related to multidrug resistance. Phage therapy is one of the most promising alternative therapeutic strategies to antibiotics. Nonetheless, only very few phages active against this bacterial species have been described. In the present study, we showed that phage training can be used to extend the host range of polyvalent Kayvirus phages within the Staphylococcus genera to include S. epidermidis species. In the context of rapid development of phage therapy, in vitro forced adaptation of previously characterized phages could be an appealing alternative to fastidious repeated isolation of new phages to improve the therapeutic potential of a phage collection.

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抗金黄色葡萄球菌治疗噬菌体对表皮葡萄球菌多重耐药分离物的治疗潜力受到序列间和序列内类型特异性的限制。
噬菌体疗法似乎是解决耐多药细菌(包括葡萄球菌)问题的一种很有前途的方法。然而,大多数抗金黄色葡萄球菌噬菌体都以金黄色葡萄球菌为特征,而针对表皮葡萄球菌的噬菌体活性的研究数量有限。我们研究了噬菌体训练的潜力,以扩大两种抗金黄色葡萄球菌噬菌体对表皮葡萄球菌分离物的宿主范围。我们采用阿佩尔曼斯方案,将 Kayvirus 和 Silviavirus 混合噬菌体反复暴露于七种具有代表性的鼻腔相关序列类型(ST)的表皮葡萄球菌菌株,其中包括在全球范围内传播的 ST2。我们只观察到 Kayvirus 混合物对其中两种菌株(ST2 或 ST35)的活性有所提高。从使用这两种菌株(5 株/株)的训练混合物中分离出的噬菌体亚群表现出不同的进化表型,仅对其分离菌株或相同 ST 的菌株具有活性。值得注意的是,16/47 株 ST2 菌株对其中一组训练有素的噬菌体易感。对祖先噬菌体基因组和训练有素的噬菌体基因组进行了比较基因组分析,以确定这种特异性活性的潜在细菌决定因素。然而,与祖先噬菌体相比,少数训练有素的噬菌体基因的核苷酸序列发生了改变,影响了相应的蛋白质,其中每个噬菌体基因组有 2 到 4 个基因发生了改变,这些改变是每组噬菌体亚群所特有的,表现出不同的宿主范围。结果表明,抗金黄色葡萄球菌噬菌体可以适应表皮葡萄球菌分离物,但具有ST间和ST内特异性。其临床重要性主要与多重耐药性有关。噬菌体疗法是最有希望替代抗生素的治疗策略之一。然而,目前只有极少数噬菌体对这种细菌具有活性。在本研究中,我们发现噬菌体训练可用于扩大葡萄球菌属中多价 Kayvirus 噬菌体的宿主范围,将表皮葡萄球菌也包括在内。在噬菌体疗法快速发展的背景下,体外强制适应先前表征的噬菌体可能是一种有吸引力的替代方法,可替代快速重复分离新噬菌体来提高噬菌体收集的治疗潜力。
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来源期刊
mSystems
mSystems Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
10.50
自引率
3.10%
发文量
308
审稿时长
13 weeks
期刊介绍: mSystems™ will publish preeminent work that stems from applying technologies for high-throughput analyses to achieve insights into the metabolic and regulatory systems at the scale of both the single cell and microbial communities. The scope of mSystems™ encompasses all important biological and biochemical findings drawn from analyses of large data sets, as well as new computational approaches for deriving these insights. mSystems™ will welcome submissions from researchers who focus on the microbiome, genomics, metagenomics, transcriptomics, metabolomics, proteomics, glycomics, bioinformatics, and computational microbiology. mSystems™ will provide streamlined decisions, while carrying on ASM''s tradition of rigorous peer review.
期刊最新文献
Effect of combined probiotics and doxycycline therapy on the gut-skin axis in rosacea. Stable, multigenerational transmission of the bean seed microbiome despite abiotic stress. Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections. Gut and oral microbial compositional differences in women with breast cancer, women with ductal carcinoma in situ, and healthy women. Metagenomic sequencing of CRISPRs as a new marker to aid in personal identification with low-biomass samples.
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