S6 CRISPR_target_results from Genome-wide correlation analysis suggests different roles of CRISPR-Cas systems in the acquisition of antibiotic resistance genes in diverse species.

CRISPR-Cas systems are widespread in bacterial and archaeal genomes, and in their canonical role in phage defence, they confer a fitness advantage. However, CRISPR-Cas may also hinder the uptake of potentially beneficial genes. This is particularly true under antibiotic selection, where preventing the uptake of antibiotic resistance genes could be detrimental. Newly discovered features within these evolutionary dynamics are anti-CRISPR genes, which inhibit specific CRISPR-Cas systems. We hypothesized that selection for antibiotic resistance might have resulted in an accumulation of anti-CRISPR genes in genomes that harbour CRISPR-Cas systems and horizontally acquired antibiotic resistance genes. To assess that question, we analysed correlations between the CRISPR-Cas, anti-CRISPR and antibiotic resistance gene content of 104 947 reference genomes, including 5677 different species. In most species, the presence of CRISPR-Cas systems did not correlate with the presence of antibiotic resistance genes. However, in some clinically important species, we observed either a positive or negative correlation of CRISPR-Cas with antibiotic resistance genes. Anti-CRISPR genes were common enough in four species to be analysed. In <i>Pseudomonas aeruginosa</i>, the presence of anti-CRISPRs was associated with antibiotic resistance genes. This analysis indicates that the role of CRISPR-Cas and anti-CRISPRs in the spread of antibiotic resistance, is likely to be very different in particular pathogenic species and clinical environments.This article is part of the theme issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.

CRISPR-Cas系统（CRISPR-Cas systems）广泛分布于细菌与古菌基因组中，其在噬菌体防御中的经典功能可赋予宿主进化适合度优势。然而，CRISPR-Cas系统也可能阻碍潜在有益基因的获取。这一点在抗生素选择压力下尤为突出：此时若阻止抗生素抗性基因的获取，反而会对宿主造成不利影响。抗CRISPR基因（anti-CRISPR genes）是近期在这类进化动态中被发现的新型特征，这类基因可特异性抑制CRISPR-Cas系统的功能。我们提出假说：抗生素抗性的选择压力，可能导致同时携带CRISPR-Cas系统与水平获得性抗生素抗性基因的基因组中，抗CRISPR基因的丰度显著积累。为验证这一假说，我们对涵盖5677个不同物种的104947个参考基因组进行了分析，探究CRISPR-Cas系统、抗CRISPR基因与抗生素抗性基因的含量相关性。在绝大多数物种中，CRISPR-Cas系统的存在与抗生素抗性基因的携带并无显著关联。但在部分临床重要物种中，我们观察到CRISPR-Cas系统与抗生素抗性基因的携带呈现正相关或负相关。抗CRISPR基因在四个物种中分布足够广泛，可用于开展针对性分析。在铜绿假单胞菌（*Pseudomonas aeruginosa*）中，抗CRISPR基因的存在与抗生素抗性基因的携带显著相关。本分析结果表明，CRISPR-Cas系统与抗CRISPR基因在抗生素抗性传播中的作用，在特定致病物种与临床环境中可能存在显著差异。本文属于“原核生物CRISPR-Cas适应性免疫系统的生态与进化”专题议题的组成部分。