@article{hill_miller_klaenhammer_1991, title={INVIVO GENETIC EXCHANGE OF A FUNCTIONAL DOMAIN FROM A TYPE-II A METHYLASE BETWEEN LACTOCOCCAL PLASMID PTR2030 AND A VIRULENT BACTERIOPHAGE}, volume={173}, ISSN={["0021-9193"]}, DOI={10.1128/jb.173.14.4363-4370.1991}, abstractNote={The conjugative plasmid pTR2030 confers bacteriophage resistance to lactococci by two independent mechanisms, an abortive infection mechanism (Hsp+) and a restriction and modification system (R+/M+). pTR2030 transconjugants of lactococcal strains are used in the dairy industry to prolong the usefulness of mesophilic starter cultures. One bacteriophage which has emerged against a pTR2030 transconjugant is not susceptible to either of the two defense systems encoded by the plasmid. Phage nck202.50 (phi 50) is completely resistant to restriction by pTR2030. A region of homology between pTR2030 and phi 50 was subcloned, physically mapped, and sequenced. A region of 1,273 bp was identical in both plasmid and phage, suggesting that the fragment had recently been transferred between the two genomes. Sequence analysis confirmed that the transferred region encoded greater than 55% of the amino domain of the structural gene for a type II methylase designated LlaI. The LlaI gene is 1,869 bp in length and shows organizational similarities to the type II A methylase FokI. In addition to the amino domain, upstream sequences, possibly containing the expression signals, were present on the phage genome. The phage phi 50 fragment containing the methylase amino domain, designated LlaPI, when cloned onto the shuttle vector pSA3 was capable of modifying another phage genome in trans. This is the first report of the genetic exchange between a bacterium and a phage which confers a selective advantage on the phage. Definition of the LlaI system on pTR2030 provides the first evidence that type II systems contribute to restriction and modification phenotypes during host-dependent replication of phages in lactococci.}, number={14}, journal={JOURNAL OF BACTERIOLOGY}, author={HILL, C and MILLER, LA and KLAENHAMMER, TR}, year={1991}, month={Jul}, pages={4363–4370} }
 @article{hill_massey_klaenhammer_1991, title={Rapid method to characterize lactococcal bacteriophage genomes}, volume={57}, number={1}, journal={Applied and Environmental Microbiology}, author={Hill, C. and Massey, I. J. and Klaenhammer, T. R.}, year={1991}, pages={283} }
 @article{hill_miller_klaenhammer_1991, title={THE BACTERIOPHAGE RESISTANCE PLASMID PTR2030 FORMS HIGH-MOLECULAR-WEIGHT MULTIMERS IN LACTOCOCCI}, volume={25}, ISSN={["0147-619X"]}, DOI={10.1016/0147-619X(91)90021-N}, abstractNote={Lactococcus lactis ME2 can transfer a 46-kb plasmid, pTR2030, which encodes abortive phage infection (Hsp) and restriction/modification (R/M) activities. pTR2030 can be detected as a monomeric plasmid in transconjugants at low copy number, but not in ME2. pTR2030-specific probes were cloned and used to determine the location of the element in ME2. No homology was observed between these pTR2030-specific probes and the CsCl-purified plasmid content of ME2. However, probes specific for pTR2030 hybridized strongly to a high-molecular-weight moiety, and not to chromosomal DNA, in total DNA isolated by a gentle lysis procedure. The absence of junction fragments indicates that pTR2030 forms high-molecular-weight multimers in lactococci. A phage-sensitive derivative of ME2, L. lactis N1, is cured of pTR2030 and no longer possesses the high-molecular-weight species. When pTR2030 was reintroduced to N1 via conjugation, an ME2-like phage-insensitive phenotype was restored. pTR2030 could remain as a detectable monomeric plasmid in the N1 transconjugants or could revert to the high-molecular-weight Structure.}, number={2}, journal={PLASMID}, author={HILL, C and MILLER, LA and KLAENHAMMER, TR}, year={1991}, month={Mar}, pages={105–112} }
 @article{hill_massey_klaenhammer_1990, title={A rapid method to identify lactococcal bacteriophages by restriction analysis}, volume={73}, journal={Journal of Dairy Science}, author={Hill, C. and Massey, I. J. and Klaenhammer, T. R.}, year={1990}, pages={73} }
 @article{hill_miller_klaenhammer_1990, title={CLONING, EXPRESSION, AND SEQUENCE DETERMINATION OF A BACTERIOPHAGE FRAGMENT ENCODING BACTERIOPHAGE RESISTANCE IN LACTOCOCCUS-LACTIS}, volume={172}, ISSN={["0021-9193"]}, DOI={10.1128/jb.172.11.6419-6426.1990}, abstractNote={A number of host-encoded phage resistance mechanisms have been described in lactococci. However, the phage genome has not been exploited as a source of additional resistance determinants. A 4.5-kb BamHI-HindIII fragment of phage nck202.50 (phi 50) was subcloned in streptococcus-Escherichia coli shuttle plasmid pSA3 and introduced into Lactococcus lactis NCK203 and MG1363 by protoplast transformation. This cloned phage fragment directed a bacteriophage resistance phenotype designated Per (phage-encoded resistance). Both phi 50 and a distantly related phage, nck202.48 (phi 48), formed small plaques on strain NCK213 at a slightly reduced efficiency of plaquing on the Per+ host. The per locus was further reduced to a 1.4-kb fragment through in vitro deletion analysis. The 1.4-kb fragment was sequenced, and the Per phenotype was found to be associated with a ca. 500-bp region rich in direct and inverted repeats. We present evidence that the Per region contains a phage origin of replication which, in trans, may interfere with phage replication by titration of DNA polymerase or other essential replication factors. It was demonstrated that the Per+ phenotype is not a result of reduced adsorption or action of a restriction and modification system. Per+ activity was not detected against six independent phages which were previously shown to be sensitive to the Hsp+ mechanism. The mutually exclusive resistance mechanisms could be combined to confer resistance to both types of phages (Hsp resistant and Per resistant) in a single host. This is the first description in lactococci of a phage resistance phenotype, other than superinfection immunity, originating from a lactococcal phage genome.}, number={11}, journal={JOURNAL OF BACTERIOLOGY}, author={HILL, C and MILLER, LA and KLAENHAMMER, TR}, year={1990}, month={Nov}, pages={6419–6426} }
 @article{hill_miller_klaenhammer_1990, title={Nucleotide sequence and distribution of the pTR2030 resistance determinant (hsp) which aborts bacteriophage infection in lactococci}, volume={56}, number={7}, journal={Applied and Environmental Microbiology}, author={Hill, C. and Miller, L. A. and Klaenhammer, T. R.}, year={1990}, pages={2255} }
 @article{hill_pierce_klaenhammer_1989, title={The conjugative plasmid pTR2030 encodes two bacteriophage defense mechanisms in lactococci, restriction modification (R+/M+) and abortive infection (Hsp+)}, volume={55}, number={9}, journal={Applied and Environmental Microbiology}, author={Hill, C. and Pierce, K. and Klaenhammer, T. R.}, year={1989}, pages={2416} }