Landscape of New Nuclease-Containing Antiphage Systems in Escherichia coli and the Counterdefense Roles of Bacteriophage T4 Genome Modifications

• DOI: 10.1128/jvi.00599-23
• Publication Date: 2023-06-12T14:00:25Z
• Authors: Shuangshuang Wang; Erchao Sun; Yuepeng Liu; Baoqi Yin; Xueqi Zhang; Mengling Li; Qi Huang; Chen Tan; Ping Qian; Venigalla B. Rao; Pan Tao
• Keywords: Nuclease

Many phages, such as T4, protect their genomes against the nucleases of bacterial restriction-modification (R-M) and CRISPR-Cas systems through covalent modification genomes. Recent studies have revealed many novel nuclease-containing antiphage systems, raising question role phage genome modifications in countering these systems. Here, by focusing on T4 its host Escherichia coli, we depicted landscape new E. coli demonstrated roles Our analysis identified at least 17 defense with type III Druantia being most abundant system, followed Zorya, Septu, Gabija, AVAST 4, qatABCD. Of these, 8 were found to be active infection. During replication 5-hydroxymethyl dCTP is incorporated into newly synthesized DNA instead dCTP. The 5-hydroxymethylcytosines (hmCs) are further modified glycosylation form glucosyl-5-hydroxymethylcytosine (ghmC). data showed that ghmC abolished activities Shedu, Restriction-like, Druantia, qatABCD anti-phage last two can also counteracted hmC modification. Interestingly, Restriction-like system specifically restricts containing an hmC-modified genome. cannot abolish SspBCDE, mzaABCDE, although it reduces efficiency. study reveals multidimensional strategies complex genomic IMPORTANCE Cleavage foreign a well-known mechanism used bacteria themselves from infections. Two R-M CRISPR-Cas, both contain cleave specific mechanisms. However, phages evolved different modify prevent cleavage. various archaea. no systematically investigated species. In addition, remains unknown. using all 2,289 available NCBI. reveal