@article{madsen_mills_djordjevic_israelsen_klaenhammer_2001, title={Analysis of the genetic switch and replication region of a P335-type bacteriophage with an obligate lytic lifestyle on Lactococcus lactis}, volume={67}, ISSN={["1098-5336"]}, DOI={10.1128/AEM.67.3.1128-1139.2001}, abstractNote={The DNA sequence of the replication module, part of the lysis module, and remnants of a lysogenic module from the lytic P335 species lactococcal bacteriophage phi31 was determined, and its regulatory elements were investigated. The identification of a characteristic genetic switch including two divergent promoters and two cognate repressor genes strongly indicates that phi31 was derived from a temperate bacteriophage. Regulation of the two early promoters was analyzed by primer extension and transcriptional promoter fusions to a lacLM reporter. The regulatory behavior of the promoter region differed significantly from the genetic responses of temperate Lactococcus lactis phages. The cro gene homologue regulates its own production and is an efficient repressor of cI gene expression. No detectable cI gene expression could be measured in the presence of cro. cI gene expression in the absence of cro exerted minor influences on the regulation of the two promoters within the genetic switch. Homology comparisons revealed a replication module which is most likely expressed from the promoter located upstream of the cro gene homologue. The replication module encoded genes with strong homology to helicases and primases found in several Streptococcus thermophilus phages. Downstream of the primase homologue, an AT-rich noncoding origin region was identified. The characteristics and location of this region and its ability to reduce the efficiency of plaquing of phi31 10(6)-fold when present at high copy number in trans provide evidence for identification of the phage origin of replication. Phage phi31 is an obligately lytic phage that was isolated from commercial dairy fermentation environments. Neither a phage attachment site nor an integrase gene, required to establish lysogeny, was identified, explaining its lytic lifestyle and suggesting its origin from a temperate phage ancestor. Several regions showing extensive DNA and protein homologies to different temperate phages of Lactococcus, Lactobacillus, and Streptococcus were also discovered, indicating the likely exchange of DNA cassettes through horizontal gene transfer in the dynamic ecological environment of dairy fermentations.}, number={3}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Madsen, SM and Mills, D and Djordjevic, G and Israelsen, H and Klaenhammer, TR}, year={2001}, month={Mar}, pages={1128–1139} }
 @misc{klaenhammer_conkling_o'sullivan_djordjevic_walker_taylor_1998, title={Bacteriophage-triggered cell suicide systems and fermentation methods employing the same}, volume={5,792,625}, number={1998 Aug. 11}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Klaenhammer, T. R. and Conkling, M. A. and O'Sullivan, D. and Djordjevic, G. and Walker, S. A. and Taylor, C. G.}, year={1998} }
 @misc{djordjevic_klaenhammer_1998, title={Inducible gene expression systems in Lactococcus lactis}, volume={9}, ISSN={["1073-6085"]}, DOI={10.1007/BF02760814}, number={2}, journal={MOLECULAR BIOTECHNOLOGY}, author={Djordjevic, GM and Klaenhammer, TR}, year={1998}, month={Apr}, pages={127–139} }
 @article{djordjevic_osullivan_walker_conkling_klaenhammer_1997, title={A triggered-suicide system designed as a defense against bacteriophages}, volume={179}, ISSN={["0021-9193"]}, DOI={10.1128/jb.179.21.6741-6748.1997}, abstractNote={A novel bacteriophage protection system for Lactococcus lactis based on a genetic trap, in which a strictly phage-inducible promoter isolated from the lytic phage phi31 is used to activate a bacterial suicide system after infection, was developed. The lethal gene of the suicide system consists of the three-gene restriction cassette LlaIR+, which is lethal across a wide range of gram-positive bacteria. The phage-inducible trigger promoter (phi31P) and the LlaIR+ restriction cassette were cloned in Escherichia coli on a high-copy-number replicon to generate pTRK414H. Restriction activity was not apparent in E. coli or L. lactis prior to phage infection. In phage challenges of L. lactis(pTRK414H) with phi31, the efficiency of plaquing was lowered to 10(-4) and accompanied by a fourfold reduction in burst size. Center-of-infection assays revealed that only 15% of infected cells released progeny phage. In addition to phage phi31, the phi31P/LlaIR+ suicide cassette also inhibited four phi31-derived recombinant phages at levels at least 10-fold greater than that of phi31. The phi31P/LlaIR+-based suicide system is a genetically engineered form of abortive infection that traps and eliminates phages potentially evolving in fermentation environments by destroying the phage genome and killing the propagation host. This type of phage-triggered suicide system could be designed for any bacterium-phage combination, given a universal lethal gene and an inducible promoter which is triggered by the infecting bacteriophage.}, number={21}, journal={JOURNAL OF BACTERIOLOGY}, author={Djordjevic, GM and OSullivan, DJ and Walker, SA and Conkling, MA and Klaenhammer, TR}, year={1997}, month={Nov}, pages={6741–6748} }
 @article{djordjevic_klaenhammer_1997, title={Bacteriophage-triggered defense systems: Phage adaptation and design improvements}, volume={63}, number={11}, journal={Applied and Environmental Microbiology}, author={Djordjevic, G. M. and Klaenhammer, T. R.}, year={1997}, pages={4370–4376} }
 @misc{djordjevic_klaenhammer_1997, title={Genes and gene expression in Lactococcus bacteriophages}, volume={7}, ISSN={["0958-6946"]}, DOI={10.1016/S0958-6946(97)00060-5}, abstractNote={Lactococcus lactis is extensively used in the production of cheese and cultured dairy products in industrial fermentations worldwide. Bacteriophage infection of L. lactis imposes a constant threat to the fermentation industry and represents the major cause of fermentation failure. Numerous phage defense strategies have been developed over the years to protect industrial starter cultures, particularly L. lactis. Numerous genes from lactococcal bacteriophages have been cloned and characterized and mechanisms that regulate their expression elucidated. Complete genome sequences of several L. lactis bacteriophages have also been determined. This accumulation of genetic information on lactococcal bacteriophages has led to a better understanding of the phage life cycle, host interactions, relationships between lactococcal phages, and possible patterns of phage evolution. These advances in molecular biology of lactococcal bacteriophages will be discussed with a view towards the development of novel and more effective phage defenses.}, number={8-9}, journal={INTERNATIONAL DAIRY JOURNAL}, author={Djordjevic, GM and Klaenhammer, TR}, year={1997}, pages={489–508} }