Evolutionary Rationale for Phages as Complements of Antibiotics.

Antibiotic-resistant bacterial infections are a major concern to public health. Phage therapy has been proposed as a promising alternative to antibiotics, but an increasing number of studies suggest that both of these antimicrobial agents in combination are more effective in controlling pathogenic bacteria than either alone. We advocate the use of phages in combination with antibiotics and present the evolutionary basis for our claim. In addition, we identify compelling challenges for the realistic application of phage-antibiotic combined therapy.

[1]  Katie Kingwell Bacteriophage therapies re-enter clinical trials , 2015, Nature Reviews Drug Discovery.

[2]  M. Hochberg,et al.  Back to the future: evolving bacteriophages to increase their effectiveness against the pathogen Pseudomonas aeruginosa PAO1 , 2013, Evolutionary applications.

[3]  J. Laakso,et al.  Phage-Driven Loss of Virulence in a Fish Pathogenic Bacterium , 2012, PloS one.

[4]  J. Usall,et al.  Biopreservative methods to control the growth of foodborne pathogens on fresh-cut lettuce. , 2015, International journal of food microbiology.

[5]  R. Müller,et al.  Cystobactamids: myxobacterial topoisomerase inhibitors exhibiting potent antibacterial activity. , 2014, Angewandte Chemie.

[6]  Franklin L. Nobrega,et al.  Revisiting phage therapy: new applications for old resources. , 2015, Trends in microbiology.

[7]  C. Townsend,et al.  Reconceptualizing synergism and antagonism among multiple stressors , 2015, Ecology and evolution.

[8]  B. Shapiro,et al.  Evolutionary consequences of intra-patient phage predation on microbial populations , 2014, eLife.

[9]  W. Hardt,et al.  Antibiotic Treatment Selects for Cooperative Virulence of Salmonella Typhimurium , 2014, Current Biology.

[10]  David Laehnemann,et al.  When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load: The Smile-Frown Transition , 2013, PLoS biology.

[11]  S. Lory,et al.  Fitness cost of antibiotic susceptibility during bacterial infection , 2015, Science Translational Medicine.

[12]  B. Grenfell,et al.  The potential impact of coinfection on antimicrobial chemotherapy and drug resistance. , 2015, Trends in microbiology.

[13]  C. Ubeda,et al.  Staphylococcal pathogenicity island interference with helper phage reproduction is a paradigm of molecular parasitism , 2012, Proceedings of the National Academy of Sciences.

[14]  Mahmoud Y. Alkawareek,et al.  Synergistic phage-antibiotic combinations for the control of Escherichia coli biofilms in vitro. , 2012, FEMS immunology and medical microbiology.

[15]  R. Donlan,et al.  Bacteriophage-Mediated Control of a Two-Species Biofilm Formed by Microorganisms Causing Catheter-Associated Urinary Tract Infections in an In Vitro Urinary Catheter Model , 2014, Antimicrobial Agents and Chemotherapy.

[16]  S. Chhibber,et al.  Co-Therapy Using Lytic Bacteriophage and Linezolid: Effective Treatment in Eliminating Methicillin Resistant Staphylococcus aureus (MRSA) from Diabetic Foot Infections , 2013, PloS one.

[17]  J. Dennis,et al.  Burkholderia cepacia Complex Phage-Antibiotic Synergy (PAS): Antibiotics Stimulate Lytic Phage Activity , 2014, Applied and Environmental Microbiology.

[18]  A. P. Krueger,et al.  OBSERVATIONS ON THE EFFECT OF PENICILLIN ON THE REACTION BETWEEN PHAGE AND STAPHYLOCOCCI , 1948, The Journal of General Physiology.

[19]  V. Aleksić,et al.  Phage-antibiotic synergism: a possible approach to combatting Pseudomonas aeruginosa. , 2013, Research in microbiology.

[20]  Alexander G. Fletcher,et al.  Steering Evolution with Sequential Therapy to Prevent the Emergence of Bacterial Antibiotic Resistance , 2015, PLoS Comput. Biol..

[21]  A. Donoghue,et al.  Therapeutic efficacy of bacteriophage and Baytril (enrofloxacin) individually and in combination to treat colibacillosis in broilers. , 2004, Poultry science.

[22]  Z. Baharoglu,et al.  Vibrio cholerae Triggers SOS and Mutagenesis in Response to a Wide Range of Antibiotics: a Route towards Multiresistance , 2011, Antimicrobial Agents and Chemotherapy.

[23]  Benjamin S Halpern,et al.  Interactive and cumulative effects of multiple human stressors in marine systems. , 2008, Ecology letters.

[24]  H. Goossens,et al.  Antibiotic resistance—the need for global solutions , 2013, BDJ.

[25]  S. Foster,et al.  Clonal Expansion during Staphylococcus aureus Infection Dynamics Reveals the Effect of Antibiotic Intervention , 2014, PLoS pathogens.

[26]  S. Chhibber,et al.  Restricting ciprofloxacin-induced resistant variant formation in biofilm of Klebsiella pneumoniae B5055 by complementary bacteriophage treatment. , 2009, The Journal of antimicrobial chemotherapy.

[27]  R. Süssmuth,et al.  The gyrase inhibitor albicidin consists of p-aminobenzoic acids and cyanoalanine. , 2015, Nature chemical biology.

[28]  J. Pachón,et al.  Attenuated virulence of a slow-growing pandrug-resistant Acinetobacter baumannii is associated with decreased expression of genes encoding the porins CarO and OprD-like. , 2011, International journal of antimicrobial agents.

[29]  M. Loessner,et al.  Bacteriophage P100 for control of Listeria monocytogenes in foods: genome sequence, bioinformatic analyses, oral toxicity study, and application. , 2005, Regulatory toxicology and pharmacology : RTP.

[30]  G. Salmond,et al.  Exploitation of a new flagellatropic phage of Erwinia for positive selection of bacterial mutants attenuated in plant virulence: towards phage therapy , 2010, Journal of applied microbiology.

[31]  M. Hochberg,et al.  A Window of Opportunity to Control the Bacterial Pathogen Pseudomonas aeruginosa Combining Antibiotics and Phages , 2014, PloS one.

[32]  Puey Ounjai,et al.  Phage–host interplay: examples from tailed phages and Gram-negative bacterial pathogens , 2014, Front. Microbiol..

[33]  S. Chhibber,et al.  Methicillin-Resistant Staphylococcus aureus Phage Plaque Size Enhancement Using Sublethal Concentrations of Antibiotics , 2012, Applied and Environmental Microbiology.

[34]  R. P. Ross,et al.  Phage therapy in the food industry. , 2014, Annual review of food science and technology.

[35]  Troy Day,et al.  The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy , 2011, Proceedings of the National Academy of Sciences.

[36]  S. Scheu,et al.  Predators promote defence of rhizosphere bacterial populations by selective feeding on non-toxic cheaters , 2009, The ISME Journal.

[37]  Christian Melander,et al.  Combination approaches to combat multidrug-resistant bacteria. , 2013, Trends in biotechnology.

[38]  Troy Day,et al.  The path of least resistance: aggressive or moderate treatment? , 2014, Proceedings of the Royal Society B: Biological Sciences.

[39]  I. Okeke Poverty and Root Causes of Resistance in Developing Countries , 2010 .

[40]  P. Volberding,et al.  Antiretroviral therapy and management of HIV infection , 2010, The Lancet.

[41]  E. Änggård,et al.  A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic‐resistant Pseudomonas aeruginosa; a preliminary report of efficacy , 2009, Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery.

[42]  M. Kutateladze,et al.  Bacteriophages as potential new therapeutics to replace or supplement antibiotics. , 2010, Trends in biotechnology.

[43]  J. Duval,et al.  Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium. , 1988, The New England journal of medicine.

[44]  N. Chanishvili Phage therapy--history from Twort and d'Herelle through Soviet experience to current approaches. , 2012, Advances in virus research.

[45]  Timothy K Lu,et al.  Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy , 2009, Proceedings of the National Academy of Sciences.

[46]  S. Reardon Antibiotic resistance sweeping developing world , 2014, Nature.

[47]  Daniel Kalman,et al.  Aligning antimicrobial drug discovery with complex and redundant host-pathogen interactions. , 2009, Cell host & microbe.

[48]  Paul S Mischel,et al.  A tale of two approaches: complementary mechanisms of cytotoxic and targeted therapy resistance may inform next-generation cancer treatments. , 2013, Carcinogenesis.

[49]  A. Kirby Synergistic Action of Gentamicin and Bacteriophage in a Continuous Culture Population of Staphylococcus aureus , 2012, PloS one.

[50]  B. Brunelle,et al.  Fluoroquinolone induction of phage-mediated gene transfer in multidrug-resistant Salmonella. , 2015, International journal of antimicrobial agents.

[51]  M. Winterhalter,et al.  The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria , 2008, Nature Reviews Microbiology.

[52]  K. Lewis,et al.  A new antibiotic kills pathogens without detectable resistance , 2015, Nature.

[53]  S. West,et al.  Cooperation, Quorum Sensing, and Evolution of Virulence in Staphylococcus aureus , 2013, Infection and Immunity.

[54]  A. Buckling,et al.  Phages limit the evolution of bacterial antibiotic resistance in experimental microcosms , 2012, Evolutionary applications.

[55]  G. Bou,et al.  Antimicrobial Resistance and Virulence: a Successful or Deleterious Association in the Bacterial World? , 2013, Clinical Microbiology Reviews.

[56]  J. Bull,et al.  Population and evolutionary dynamics of phage therapy , 2004, Nature Reviews Microbiology.

[57]  H. Krisch,et al.  Phage-Antibiotic Synergy (PAS): β-Lactam and Quinolone Antibiotics Stimulate Virulent Phage Growth , 2007, PloS one.

[58]  J. Gill,et al.  Phage therapy redux—What is to be done? , 2015, Science.

[59]  M. Santamaría,et al.  Main features on tailed phage, host recognition and DNA uptake. , 2004, Frontiers in bioscience : a journal and virtual library.