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

Autor:	Kolenda C; Service de bactériologie, Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.; Equipe StaPath, CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France., Bonhomme M; Service de bactériologie, Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.; Equipe StaPath, CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France., Medina M; Service de bactériologie, Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.; Equipe StaPath, CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France., Pouilly M; Service de bactériologie, Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France., Rousseau C; Service de bactériologie, Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France., Troesch E; Service de bactériologie, Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France., Martins-Simoes P; Service de bactériologie, Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.; Equipe StaPath, CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France., Stegger M; Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.; Antimicrobial Resistance and Infectious Diseases Laboratory, Harry Butler Institute, Murdoch University, Perth, Australia., Verhoeven PO; GIMAP Team, CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France.; Faculty of Medicine, Université Jean Monnet St-Etienne, St-Etienne, France.; Department of Infectious Agents and Hygiene, University Hospital of St-Etienne, St-Etienne, France., Laumay F; Service de bactériologie, Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.; Equipe StaPath, CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France.; Faculté de Pharmacie, Université Claude Bernard Lyon 1, Lyon, France., Laurent F; Service de bactériologie, Centre National de Référence des Staphylocoques, Institut des Agents Infectieux, Hospices Civils de Lyon, Lyon, France.; Equipe StaPath, CIRI, Centre International de Recherche en Infectiologie, Inserm U1111, Université Claude Bernard Lyon 1, CNRS UMR5308, ENS de Lyon, Lyon, France.; Faculté de Pharmacie, Université Claude Bernard Lyon 1, Lyon, France.
Jazyk:	angličtina
Zdroj:	MSystems [mSystems] 2024 Oct 22; Vol. 9 (10), pp. e0085024. Date of Electronic Publication: 2024 Sep 09.
DOI:	10.1128/msystems.00850-24
Abstrakt:	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.Importance S. 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. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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