Leinweber Helena, Sieber Raphael N, Bojer Martin S, Larsen Jesper, Ingmer Hanne
Department of Veterinary and Animal Sciences, University of Copenhagen, Stigbøjlen 4, 1870 Copenhagen, Denmark.
Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen, Denmark.
Access Microbiol. 2023 Jun 9;5(6). doi: 10.1099/acmi.0.000583.v4. eCollection 2023.
Prophages of the ΦSa3int family are commonly found in human-associated strains of where they encode factors for evading the human innate immune system. In contrast, they are usually absent in livestock-associated methicillin-resistant (LA-MRSA) strains where the phage attachment site is mutated compared to the human strains. However, ΦSa3int phages have been found in a subset of LA-MRSA strains belonging to clonal complex 398 (CC398), including a lineage that is widespread in pig farms in Northern Jutland, Denmark. This lineage contains amino acid changes in the DNA topoisomerase IV and the DNA gyrase encoded by and , respectively, which have been associated with fluoroquinolone (FQ) resistance. As both of these enzymes are involved in DNA supercoiling, we speculated that the mutations might impact recombination between the ΦSa3int phage and the bacterial chromosome. To examine this, we introduced the FQ resistance mutations into 8325-4 that carry the mutated CC398-like bacterial attachment site for ΦSa3int phages. When monitoring phage integration and release of Φ13, a well-described representative of the ΦSa3int phage family, we did not observe any significant differences between the FQ-resistant mutant and the wild-type strain. Thus our results suggest that mutations in and do not contribute to the presence of the ΦSa3int phages in LA-MRSA CC398.
ΦSa3int家族的原噬菌体常见于与人类相关的菌株中，它们编码逃避人类先天免疫系统的因子。相比之下，它们通常不存在于与家畜相关的耐甲氧西林金黄色葡萄球菌（LA-MRSA）菌株中，与人类菌株相比，这些菌株中的噬菌体附着位点发生了突变。然而，在属于克隆复合体398（CC398）的一部分LA-MRSA菌株中发现了ΦSa3int噬菌体，包括在丹麦日德兰半岛北部猪场广泛存在的一个谱系。该谱系在分别由parC和gyrA编码的DNA拓扑异构酶IV和DNA促旋酶中含有氨基酸变化，这与氟喹诺酮（FQ）耐药性有关。由于这两种酶都参与DNA超螺旋，我们推测这些突变可能会影响ΦSa3int噬菌体与细菌染色体之间的重组。为了研究这一点，我们将FQ耐药性突变引入携带针对ΦSa3int噬菌体的突变CC398样细菌附着位点的8325-4菌株中。当监测Φ13（ΦSa3int噬菌体家族一个广为人知的代表）的噬菌体整合和释放时，我们没有观察到FQ耐药突变体与野生型菌株之间有任何显著差异。因此，我们的结果表明，parC和gyrA中的突变对LA-MRSA CC398中ΦSa3int噬菌体的存在没有影响。
