Effect of the Abortive Infection Mechanism and Type III Toxin/Antitoxin System AbiQ on the Lytic Cycle of Lactococcus lactis Phages

Abstract

To survive in phage-containing environments, bacteria have evolved an array of antiphage systems. Similarly, phages have overcome these hurdles through various means. Here, we investigated how phages are able to circumvent the Lactococcus lactis AbiQ system, a type III toxin-antitoxin with antiviral activities. Lactococcal phage escape mutants were obtained in the laboratory, and their genomes were sequenced. Three unrelated genes of unknown function were mutated in derivatives of three distinct lactococcal siphophages: orf38 of phage P008, m1 of phage bIL170, and e19 of phage c2. One-step growth curve experiments revealed that the phage mutations had a fitness cost while transcriptional analyses showed that AbiQ modified the early-expressed phage mRNA profiles. The L. lactis AbiQ system was also transferred into Escherichia coli MG1655 and tested against several coliphages. While AbiQ was efficient against phages T4 (Myoviridae) and T5 (Siphoviridae), escape mutants of only phage 2 (Myoviridae) could be isolated. Genome sequencing revealed a mutation in gene orf210, a putative DNA polymerase. Taking these observations together, different phage genes or gene products are targeted or involved in the AbiQ phenotype. Moreover, this antiviral system is active against various phage families infecting Gram-positive and Gram-negative bacteria. A model for the mode of action of AbiQ is proposed.

Evolutionary Ecology of Prokaryotic Immune Mechanisms

“…While intraspecific diversity may be neutralized by a sufficiently high diversity of host resistance alleles, interspecific diversity (i.e., many different viruses) is likely to select for broad-range innate immune mechanisms, such as RM, Abi, and Sie, which typically provide protection against a range of phages (124,163) (Fig. 6).…”

Functional and Structural Analysis of HicA3-HicB3, a Novel Toxin-Antitoxin System of Yersinia pestis

“…The type II antitoxin is usually also a DNA-binding protein that can block the promoter region of the TA operon (15). In type III TASs, the antitoxin is an RNA that directly binds to and neutralizes the toxin protein (16,17). Most recently, three-component modules have been described and included in the list of type II TASs (18,19).…”

AbpA and AbpB provide anti-phage activity in <i>Escherichia coli</i>

“…To combat this threat, bacteria have evolved a variety of resistance mechanisms (Sturino and Klaenhammer, 2006;Labrie et al, 2010;Bikard and Marraffini, 2012). On the other hand, phages have also evolved mechanisms to overcome these bacterial anti-phage mechanisms (Otsuka and Yonesaki, 2012;Samson et al, 2013). Accordingly, phages and bacteria co-evolve (Comeau and Krisch, 2005;Kashiwagi and Yomo, 2011;Stern and Sorek, 2011).…”

“…E-mail: otsukay@dokkyomed.ac.jp bacterial toxin-antitoxin (TA) systems also have been reported to play a role in phage defense (Pecota and Wood, 1996;Hazan and Engelberg-Kulka, 2004;Fineran et al, 2009;Samson et al, 2013;Sberro et al, 2013). TA systems are broadly conserved in plasmids and bacterial chromosomes (Gerdes et al, 2005), and are implicated in many physiological roles, such as plasmid maintenance (Ogura and Hiraga, 1983;Yarmolinsky, 1995), stress response (Gerdes et al, 2005;Wang et al, 2011), bacterial persistence against antibiotics (Maisonneuve et al, 2011(Maisonneuve et al, , 2013Amato et al, 2013;Germain et al, 2013) and biofilm formation Wang et al, 2011).…”