Phages are credited with having been first described in what we now, officially, are commemorating as the 100th anniversary of their discovery. Those one-hundred years of phage history have not been lacking in excitement, controversy, and occasional convolution. One such complication is the concept of secondary infection, which can take on multiple forms with myriad consequences. The terms secondary infection and secondary adsorption, for example, can be used almost synonymously to describe virion interaction with already phage-infected bacteria, and which can result in what are described as superinfection exclusion or superinfection immunity. The phrase secondary infection also may be used equivalently to superinfection or coinfection, with each of these terms borrowed from medical microbiology, and can result in genetic exchange between phages, phage-on-phage parasitism, and various partial reductions in phage productivity that have been termed mutual exclusion, partial exclusion, or the depressor effect. Alternatively, and drawing from epidemiology, secondary infection has been used to describe phage population growth as that can occur during active phage therapy as well as upon phage contamination of industrial ferments. Here primary infections represent initial bacterial population exposure to phages while consequent phage replication can lead to additional, that is, secondary infections of what otherwise are not yet phage-infected bacteria. Here I explore the varying meanings and resultant ambiguity that has been associated with the term secondary infection. I suggest in particular that secondary infection, as distinctly different phenomena, can in multiple ways influence the success of phage-mediated biocontrol of bacteria, also known as, phage therapy.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Abedon S. 2011. Phage therapy pharmacology: calculating phage dosing. Adv Appl Microbiol. 77:10–40.
Abedon S T. 1990. Selection for lysis inhibition in bacteriophage. J Theor Biol. 146:501–511.
Abedon S T. 1992. Lysis of lysis inhibited bacteriophage T4-infected cells. J Bacteriol. 174:8073–8080.
Abedon S T. 1994. Lysis and the interaction between free phages and infected cells. In: The Molecular Biology of Bacteriophage T4. Karam J D, Kutter E, Carlson K, and Guttman B (eds). Washington DC: ASM Press, pp397–405.
Abedon S T. 1999. Bacteriophage T4 resistance to lysis-inhibition collapse. Genet Res, 74:1–11.
Abedon S T. 2008. Phage population growth: constraints, games, adaptation. In: Bacteriophage Ecology. Abedon ST (ed). Cambridge: Cambridge University Press, pp64–93.
Abedon S T. 2009a. Bacteriophage intraspecific cooperation and defection. In: Contemporary Trends in Bacteriophage Research. Adams H T (ed). Hauppauge: Nova Science Publishers, pp191–215.
Abedon S T. 2009b. Disambiguating bacteriophage pseudolysogeny: an historical analysis of lysogeny, pseudolysogeny, and the phage carrier state. In: Contemporary Trends in Bacteriophage Research. Adams H T (ed). Hauppauge: Nova Science Publishers, pp285–307.
Abedon S T. 2009c. Kinetics of phage-mediated biocontrol of bacteria. Foodborne Pathog Dis, 6:807–815.
Abedon S T. 2011a. Bacteriophages and Biofilms: Ecology, Phage Therapy, Plaques. Hauppauge: Nova Science Publishers.
Abedon S T. 2011b. Lysis from without. Bacteriophage. 1:46–49.
Abedon S T. 2012a. Phage therapy best practices. In: Bacteriophages in Health and Disease. Hyman P, Abedon S T (eds). Wallingford: CABI Press, pp256–272.
Abedon ST. 2012b. Spatial vulnerability: bacterial arrangements, microcolonies, and biofilms as responses to low rather than high phage densities. Viruses. 4:663–687.
Abedon ST. 2012c. Thinking about microcolonies as phage targets. Bacteriophage. 2:200–204.
Abedon ST. 2014. Bacteriophages as drugs: the pharmacology of phage therapy. In: Phage Therapy: Current Research and Applications. Borysowski J, Miedzybrodzki R, and Górski A (eds). Norfolk: Caister Academic Press, pp69–100.
Abedon S T, Kuhl S J, Blasdel B G, Kutter E M. 2011. Phage treatment of human infections. Bacteriophage. 1:66–85.
Abedon S T, Thomas-Abedon C. 2010. Phage therapy pharmacology. Curr Pharm Biotechnol. 11:28–47.
Adams M H. 1959. Bacteriophages. New York: InterScience.
Barron B A, Fischetti V A, Zabriskie J B. 1970. Studies of the bacteriophage kinetics of multicellular systems: a statistical model for the estimation of burst size per cell in streptococci. J Appl Bacteriol. 33:436–442.
Benzer S, Hudson W, Weidel W, Delbruck M, Stent G S, Weigle J J, Dulbecco R, Watson J D, Wollman E L. 1950. A syllabus on procedures, facts, and interpretations in phage. Viruses 1950. Delbruck M (ed). Pasadena: California Institute of Technology, pp100–147.
Berngruber T W, Weissing F J, Gandon S. 2010. Superinfection inhibition and the evolution of viral latency. J Virol, 84:10200–10208.
Bigwood T, Hudson J A, Billington C. 2009. Influence of host and bacteriophage concentrations on the inactivation of foodborne pathogenic bacteria by two phages. FEMS Microbiol Lett, 291:59–64.
Bull J J, Regoes R R. 2006. Pharmacodynamics of non-replicating viruses, bacteriocins and lysins. Proc R Soc Lond B Biol Sci, 273:2703–2712.
Chan B K, Abedon S T. 2012. Phage therapy pharmacology: phage cocktails. Adv Appl Microbiol, 78:1–23.
Chan B K, Abedon S T, Loc-Carrillo C. 2013. Phage cocktails and the future of phage therapy. Future Microbiol, 8:769–783.
Davis B M, Kimsey H H, Chang W, Waldor M K. 1999. The Vibrio cholerae O139 Calcutta bacteriophage CTXϕ is infectious and encodes a novel repressor. J Bacteriol, 181:6779–6787.
Doermann A H. 1948. Lysis and lysis inhibition with Escherichia coli bacteriophage. J Bacteriol, 55:257–275.
Espeland E M, Lipp E K, Huq A, Colwell R R. 2004. Polylysogeny and prophage induction by secondary infection in Vibrio cholerae. Environ Microbiol, 6:760–763.
Fogg P C, Allison H E, Saunders J R, McCarthy A J. 2010. Bacteriophage lambda: a paradigm revisited. J Virol, 84:6876–6879.
Fogg P C M, Gossage S M, Smith D L, Saunders J R, McCarthy A J, Allison H E. 2007. Identification of multiple integration sites for Stx-phage Φ24B in the Escherichia coli genome, description of a novel integrase and evidence for a functional anti-repressor. Microbiology. 153:4098–4110.
French R C, Graham A F, Lesley S M, van Rooyen C E. 1952. The contribution of phosphorus from T2r+ bacteriophage to progeny. J Bacteriol. 64:597–607.
Fukuda E, Kaminska K H, Bujnicki J M, Kobayashi I. 2008. Cell death upon epigenetic genome methylation: a novel function of methyl-specific deoxyribonucleases. Genome Biol. 9:R163.
Golshahi L, Seed K D, Dennis J J, Finlay W H. 2008. Toward modern inhalational bacteriophage therapy: nebulization of bacteriophages of Burkholderia cepacia complex. J Aerosol Med Pulm Drug Deliv, 21:351–360.
Hatfull G F, Hendrix R W. 2011. Bacteriophages and their genomes. Curr Opin Virol, 1:298–303.
Hendrix R W. 2008. Phage evolution. In: Bacteriophage Ecology. Abedon ST (ed). Cambridge: Cambridge University Press, pp177–194.
Hendrix R W, Smith M C M, Burns R N, Ford M E, Hatfull G F. 1999. Evolutionary relationships among diverse bacteriophages and prophages: All the world’s a phage. Proc Natl Acad Sci USA. 96:2192–2197.
Hudson J A, Billington C, Carey-Smith G, Greening G. 2005. Bacteriophages as biocontrol agents in food. J Food Prot, 68:426–437.
Hughes K A, Sutherland I W, Jones M V. 1998. Biofilm susceptibility to bacteriophage attack: the role of phage-borne polysac charide depolymerase. Microbiology. 144:3039–3047.
Hyman P, Abedon S T. 2010. Bacteriophage host range and bacterial resistance. Adv Appl Microbiol, 70:217–248.
Hyman P, Abedon S T. 2012. Smaller fleas: viruses of microorganisms. Scientifica. 2012:734023.
Iyer V N, James A P. 1978. Single-cell studies on the carrier state of bacteriophage IKe, a virus specific for conjugative plasmids of the N incompatibility and conjugative group. Can J Microbiol, 24:1595–1601.
Mann N H. 2003. Phages of the marine cyanobacterial picophytoplankton. FEMS Microbiol Rev, 27:17–34.
May R M, Anderson R M. 1983. Parasite-host coevolution. In: Coevolution. Futuyma D J, Slatkin M (eds). Sunderland: Sinauer Associates, pp186–206.
Moussa S H, Kuznetsov V, Tran T A, Sacchettini J C, Young R. 2012. Protein determinants of phage T4 lysis inhibition. Protein Sci, 21:571–582.
Moussa S H, Lawler J L, Young R. 2014. Genetic dissection of T4 lysis. J Bacteriol, 196:2201–2209.
Payne R J H, Jansen V A A. 2001. Understanding bacteriophage therapy as a density-dependent kinetic process. J Theor Biol, 208:37–48.
Payne R J H, Jansen V A A. 2003. Pharmacokinetic principles of bacteriophage therapy. Clin Pharmacokinet, 42:315–325.
Payne R J H, Phil D, Jansen V A A. 2000. Phage therapy: The peculiar kinetics of self-replicating pharmaceuticals. Clin Pharmacol Ther, 68:225–230.
Pratt J H. 1899. Secondary infection of the skin and subcutaneous tissues by the bacillus typhosus. J Boston Soc Med Sci, 3:170–173.
Ryan E M, Gorman S P, Donnelly R F, Gilmore B F. 2011. Recent advances in bacteriophage therapy: how delivery routes, formulation, concentration and timing influence the success of phage therapy. J Pharm Pharamcol, 63:1253–1264.
Sanders M E. 1987. Bacteriophages of industrial importance. In: Phage Ecology. Goyal S M, Gerba G P, Bitton G (eds). New York: John Wiley & Sons, pp211–244.
Slavcev R A, Hayes S. 2002. Rex-centric mutualism. J Bacteriol, 184:857–858.
Smith D L, Rooks D J, Fogg P C, Darby A C, Thomson N R, Mc-Carthy A J, Allison H E. 2012. Comparative genomics of Shiga toxin encoding bacteriophages. BMC Genomics, 13:311.
Stent G S. 1963. Molecular biology of bacterial viruses. San Francisco: WH Freeman and Co.
Sturino J M, Klaenhammer T R. 2006. Engineered bacteriophage-defence systems in bioprocessing. Nat Rev Microbiol, 4:395–404.
Tran T A, Struck D K, Young R. 2005. Periplasmic domains define holin-antiholin interactions in T4 lysis inhibition. J Bacteriol, 187:6631–6640.
Tran T A, Struck D K, Young R. 2007. The T4 RI antiholin has an N-terminal signal anchor release domain that targets it for degradation by DegP. J Bacteriol, 189:7618–7625.
Turner P E, Duffy S. 2008. Evolutionary ecology of multi-phage infections. In: Bacteriophage Ecology. Abedon ST (ed). Cambridge: Cambridge University Press, pp195–216.
Wei W, Krone S M. 2005. Spatial invasion by a mutant pathogen. J Theor Biol, 236:335–348.
Weinfeld H, Paigen K. 1964. Evidence for a new intermediate state of the viral chromosome during cooperative infection by host-modified lambda phage. Virology, 24:71–83.
Werner E R, Christensen J R. 1969. Infection by bacteriophage P1 and development of host-controlled restriction and modification and of lysogenic immunity. J Virol, 3:363–368.
Yamada T, Kawasaki T, Nagata S, Fujiwara A, Usami S, Fujie M. 2007. New bacteriophages that infect the phytopathogen Ralstonia solanacearum. Microbiology. 153:2630–2639.
About this article
Cite this article
Abedon, S.T. Bacteriophage secondary infection. Virol. Sin. 30, 3–10 (2015). https://doi.org/10.1007/s12250-014-3547-2