Bacteria can gain resistance to antimicrobials by acquiring and expressing genetic elements that encode resistance determinants such as efflux pumps and drug-modifying enzymes, thus hampering treatment of infection. Previously we showed that acquisition of spectinomycin resistance in a lactococcal strain was correlated with a reversible genomic inversion, but the precise location and the genes affected were unknown. Here we use long-read whole-genome sequencing to precisely define the genomic inversion and we use quantitative PCR to identify associated changes in gene expression levels. The boundaries of the inversion fall within two identical copies of a prophage-like sequence, located on the left and right replichores; this suggests possible mechanisms for inversion through homologous recombination or prophage activity. The inversion is asymmetrical in respect of the axis between the origin and terminus of the replication and modulates the expression of a SAM-dependent methyltransferase, whose heterologous expression confers resistance to spectinomycin in lactococci and that is up-regulated on exposure to spectinomycin. This study provides one of the first examples of phase variation via large-scale chromosomal inversions that confers a switch in antimicrobial resistance in bacteria and the first outside of Staphylococcus aureus.

细菌可以通过获取和表达编码抗性决定因子的遗传元件（例如外排泵和药物修饰酶）来获得对抗菌素的抗性，从而阻碍感染的治疗。以前，我们表明在乳球菌菌株中获得壮观霉素的耐药性与可逆的基因组倒置相关，但是确切的位置和受影响的基因尚不清楚。在这里，我们使用长时间阅读的全基因组测序来精确定义基因组倒置，并使用定量PCR来识别基因表达水平的相关变化。倒置的边界落在左右复制子中的一个类似噬菌体序列的两个相同副本内。这表明可能通过同源重组或原噬菌体转化的机制。反转在复制起点和终点之间的轴上是不对称的，并且调节SAM依赖性甲基转移酶的表达，其异源表达赋予乳球菌对壮观霉素的抗性，并且在暴露于壮观霉素时被上调。这项研究提供了通过大规模染色体倒置进行相变的第一个例子，它使细菌的抗药性和第一个外部细菌的耐药性发生了变化。金黄色葡萄球菌。