The reproduction of bacteriophages is quite different from that of animals or plants. If we were able to stop the process and see what is happening inside the cell, we would observe three different steps Figure 3.
At the end of the lytic cycle, the bacterium dies. Bacteriophages are, therefore, the natural enemies of bacteria. In nature, both bacteria and bacteriophages are necessary to keep microscopic ecosystems working properly. This is similar to what occurs with animals, when the predator fox and the prey hare live together in the same place, despite being enemies.
Yes, they are. We can use bacteriophages to kill bad bacteria in a way that is similar to the way we use antibiotics [ 2 ]. Moreover, bacteriophages have some advantages compared with antibiotics. For instance, antibiotics usually kill different types species of bacteria, while bacteriophages generally attack only one kind of bacteria.
Actually, a great number of scientists working on this research area have found other uses for bacteriophages. For example, bacteriophages can be used to clean hospitals or industrial surfaces, since they can destroy undesirable bacteria like disinfectants do.
It is also possible include bacteriophages in foods, which will work similar to chemical preservatives [ 3 ]. Bacteriophages will wait in the food until some bad bacteria contaminate it and, like playing hide-and-seek, when the bacteriophages find their bacterial targets, they will catch them!
Do you now believe that bacteriophages are good weapons to combat bad bacteria? The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Multidrug resistance in bacteria. Some phages produce proteins to mask the cell surface receptors, blocking new infections. This strategy also protects the newly formed phages from being inactivated as a consequence of binding to receptors coming from remains of lysed bacteria. This behavior is observed for example in phage T5, which produces lipoprotein Llp that conceals its own receptor, outer membrane protein FhuA Pedruzzi, Rosenbusch and Locher Other phages, mostly prophages Van Houte, Buckling and Westra , use membrane-anchored or membrane-associated proteins to target and block the entry of phage DNA into the bacterial cytoplasm Labrie, Samson and Moineau Such proteins act by inhibiting the formation of the channel through which DNA travels across the cell membrane, by inhibiting the phage lysozyme that degrades the peptidoglycan of the bacterial cell wall, or by changing the conformation of the proteins surrounding the ejection site to prevent translocation Bondy-Denomy et al.
Furthermore, prophages can mediate resistance through non-Sie-like mechanisms as well Fig. Another example is the phage Panchino of M. Genes encoding repressor proteins that bind phage DNA may also be found in prophages Pope et al.
They are thought to have a role in protecting the viability of the lysogenized bacteria, counteracting accidental prophage transcription events. Prophage-mediated phenotypic changes in bacteria are sometimes encoded in genetic elements called morons, which are flanked by a promoter and a transcriptional terminator and can be transcribed autonomously, independent of prophage activation Juhala et al. As with host defense systems, the discovery of phage-derived defense systems is ongoing.
Analysis of Enterobacteria P4- and P2-like prophages recently led to the discovery of genetic hotspots that encode a variety of bacterial immune mechanisms Rousset et al. The mechanisms of action of PARIS and the other systems identified in this study remain to be further uncovered. In summary, once inside the host, phages themselves can provide the bacteria with mechanisms of protection against further phage infection that favor both the bacteria and the phage.
While the mechanisms of phage resistance exhibited by bacteria seem overwhelmingly varied, phages have also developed a broad array of opposing strategies. Just as bacterial defenses target every step in the process of phage infection, every barrier imposed by bacteria has to withstand a phage counterattack Stern and Sorek In response to variations in the bacterial cell surface receptors, phages are able to change their tropism through mutations in their RBPs.
In fact, genes encoding RBPs and other proteins related to host recognition are reported to incorporate mutations at a very high frequency. This is often mediated by the activity of diversity-generating retroelements DGRs Guo et al.
These are regions that are subjected to targeted mutation by means of the exchange of two variable repeats by an error-prone reverse transcriptase Paul et al.
This type of directed mutagenesis is template dependent and affects determined adenine-specific sites, while a conserved scaffold sequence is retained to ensure stability.
This process was first described for the specificity switch of the major tropism determinant protein in Bordetella spp. Since then, more phages have been identified that benefit from these systems Benler et al.
To overcome the barrier imposed by capsules and extracellular layers, some phages became able to bind to these structures Bertozzi Silva, Storms and Sauvageau , and to degrade them using depolymerases.
These enzymes may be either expressed as part of tail spike or tail fiber proteins or released in a soluble form following lysis of infected bacteria Latka et al.
A recent review offers an overview of the diversity of phage depolymerases Knecht, Veljkovic and Fieseler Phages have also developed forms of escaping targeting by R-M systems. They can i mutate to remove restriction sites from their genome palindrome avoidance and therefore avoid recognition by REases Rocha, Danchin and Viari ; Rusinov et al. Phages can acquire point mutations or deletions in the PAM sequences or in positions of the protospacer region close to the PAM sequences i.
In general, Acrs work by either preventing recruitment of the crRNA-Cas complex to the target DNA by binding the complex or occluding the PAM sequence, or by inhibiting the endonuclease domain so that cleavage cannot take place Stanley and Maxwell Abi mechanisms can also be outsmarted by phages. Phages can avoid toxin—antitoxin mechanisms by inhibiting the protease that degrades the antitoxin, or by expressing their own antitoxin analogue Blower et al.
Furthermore, mutations in genes involved in the metabolism of nucleic acids also prove to be effective in avoiding toxin—antitoxin systems of some bacteria like Lactococcus spp. Mutations in phage genes encoding peptides that activate Abi-associated enzymes, such as the Lit activator Gol peptide in the major head protein of T4, can also result in hindering of the Abi mechanism Bingham et al.
Phages ICP1 that infect V. It is expected that phages possess countermeasures against the more newly described defense systems as well. The discovery of other new phage counterattack strategies is likely just a matter of time, as interest in bacterial defense mechanisms and phage anti-defenses continues to grow.
The number of phage therapy case studies and clinical trials performed in humans has significantly increased in these past years, as the problem of antibiotic resistance aggravates. The efficacy of phage therapy in these studies is quite variable, ranging from negative outcomes to the resolution of severe infections in human patients Table 1 ; Table S1, Supporting Information. Interestingly, while phage resistance has been shown to develop quickly in vitro , studies in humans have described both the presence Zhvania et al.
As a consequence of such variable results, there is a lack of consensus in the scientific and medical community about the potential of phages as therapeutic agents. Case studies and clinical trials of phage therapy in humans, with associated safety, and clinical and phage-resistance outcomes.
For a full list of clinical studies and case reports with phages, refer to Table S1 Supporting Information.
Successful: patient was healed. Not described: resistance was not addressed. Not identified: resistance was investigated but not found. The human immune response to bacterial infection and the specific phage-resistance mechanisms developed by the bacteria are likely behind the distinct outcomes. The development of an immune response, particularly involving neutrophils, has been shown essential for the success of phage therapy by preventing the outgrowth of phage-resistant mutants Roach et al.
Multiple studies have demonstrated that phage-resistant phenotypes often associate with decreased pathogenicity, with the strain becoming more susceptible to the human immune defenses Sumrall et al.
Receptor adaptations such as mutations in bacterial capsule, LPS and other surface components are examples of phage-resistance mechanisms that result in increased immune susceptibility Cai et al. Importantly, these surface modifications also often associate with increased antibiotic susceptibility.
This effect occurs, for example, in cases where the phage interacts with bacterial structures that function as drug efflux pumps Chan et al. By mutating the efflux pump to achieve phage resistance, bacteria lose the ability to pump out the antibiotics, thus gaining antibiotic susceptibility as a trade-off for a review of mechanisms of phage-antibiotic synergism, see e. Tagliaferri, Jansen and Horz However, phage-resistance mutations have also been shown to pleiotropically confer increased antibiotic resistance Burmeister et al.
CRISPR-Cas, R-M systems may lead to a phage-resistance phenotype that does not render the bacteria more susceptible to the immune system or to antibiotics. In such cases, resistance to phages may develop in vivo even in the presence of a strong immune response. Unfortunately, the mechanisms underlying phage resistance are seldom, if ever, investigated in human clinical studies and trials, and represent a clear knowledge gap. There are studies, however, that indicate that addressing and tackling phage resistance can lead to improved treatment outcomes.
One such study found phage-resistant clones in a patient suffering from a multidrug-resistant A. Phage-resistance was associated with loss of bacterial capsule and increased extracellular polysaccharide production, and was overcome via an iterative process of phage cocktail formulation that resulted in the resolution of the infection.
Of relevance, the phage-resistant phenotype was associated with increased antibiotic sensitivity, suggesting a fitness cost of phage-resistant mutations in vivo. In another study, the association between phage-resistance and increased antibiotic susceptibility was exploited to treat a patient with a chronic multidrug-resistant P.
The treatment consisted of a combination of the antibiotic ceftazidime and phage OMKO1, which binds to an outer membrane protein that is part of multidrug efflux systems of P. This combination explored the capacity of the phage to kill the original strain and the ability of ceftazidime to kill any emerging phage-resistant variants with mutations in the multidrug efflux system, to achieve resolution of the infection.
Characterizing the mechanisms of resistance to phages that target pathogens of interest will inform about the relevance that each phage defense system has in a clinical context, in terms of frequency with which they occur in pathogens and their association with virulence and antibiotic susceptibility of the pathogen. Furthermore, certain natively present defense systems like R-M may affect and reduce the choice of phages available to use in a therapeutic setting.
Another issue to consider is that the development of resistance as well as treatment efficacy may significantly differ when using single- or multi-phage treatment approaches, and may also vary with the timing and order of phage administration Wright et al. The more widespread use of bacteriophages for therapeutic purposes could lead to selection for phage-resistant phenotypes that arise through horizontal gene transfer of phage defense systems.
Understanding the complexity of interactions and mechanisms leading to phage resistance will aid the development of phage-based treatments with better clinical outcomes and to engineered phages that may overcome host defense systems. In this review, we have provided an overview of the current knowledge of mechanisms behind existing and developing phage resistance, and highlighted the potential knowledge gaps and clinical importance of phage resistance for phage therapeutic strategies.
While our understanding of the mechanisms behind phage resistance has expanded in recent years, many defense systems remain uncharacterized or yet undiscovered. As such, the complete picture of phage resistance development remains elusive, especially in the context of the human body. For phage therapy to move forward, it is imperative that clinical studies and trials also assess the development of resistance in a systematic manner, in which both the emergence of phage resistance and the mechanisms behind it are included in the investigation.
Sequencing technologies and genome analysis of both bacterial strains and phages may allow for the identification of defense and anti-defense systems in clinical isolates. Such data will prove invaluable for isolating and selecting candidate phages, as well as for predicting the outcome of the therapeutic intervention. Improved understanding of how defense systems affect phage therapy, combined with an increased knowledge of the anti-defense strategies employed by phages to counteract bacterial defenses, will greatly contribute to the development of more effective phage-based therapeutic approaches.
An invertible element of DNA controls phase variation of type 1 fimbriae of Escherichia coli. Google Scholar. Clustered regularly interspaced short palindromic repeats CRISPRs : the hallmark of an ingenious antiviral defense mechanism in prokaryotes. Biol Chem. Early clinical experience of bacteriophage therapy in 3 lung transplant recipients. Am J Transplant. Lessons learned from the first 10 consecutive cases of intravenous bacteriophage therapy to treat multidrug-resistant bacterial infections at a single center in the United States.
Open Forum Infect Dis. Interaction of the ocr gene 0. Nucleic Acids Res. Non-active antibiotic and bacteriophage synergism to successfully treat recurrent urinary tract infection caused by extensively drug-resistant Klebsiella pneumoniae.
Emerg Microbes Infect. Genome replication dynamics of a bacteriophage and its satellite reveal strategies for parasitism and viral restriction. A diversity-generating retroelement encoded by a globally ubiquitous Bacteroides phage. Prokaryotic viperins produce diverse antiviral molecules. Host receptors for bacteriophage adsorption.
The major head protein of bacteriophage T4 binds specifically to elongation factor Tu. J Biol Chem. Viral evasion of a bacterial suicide system by RNA-based molecular mimicry enables infectious altruism.
PLoS Genet. Prophages mediate defense against phage infection through diverse mechanisms. ISME J. Phage T5 straight tail fiber is a multifunctional protein acting as a tape measure and carrying fusogenic and muralytic activities. The effect of phage genetic diversity on bacterial resistance evolution. Pleiotropy complicates a trade-off between phage resistance and antibiotic resistance.
Three capsular polysaccharide synthesis-related glucosyltransferases, GT-1, GT-2 and WcaJ, are associated with virulence and phage sensitivity of Klebsiella pneumoniae. Front Microbiol. DOI: Epigenetic gene regulation in the bacterial world. Microbiol Mol Biol Rev. Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa. Sci Rep. Phage treatment of an aortic graft infected with Pseudomonas aeruginosa.
Evol Med Public Health. Chanishvili N. Phage therapy—history from Twort and d'Herelle through Soviet experience to current approaches. Adv Virus Res. Stochastic receptor expression allows sensitive bacteria to evade phage attack.
Part I: experiments. Biophys J. Part II: theoretical analyses. Synergy and order effects of antibiotics and phages in killing Pseudomonas aeruginosa biofilms. PLoS One. F exclusion of bacteriophage T7 occurs at the cell membrane. J Mol Biol. Identification and characterization of a novel flagellum-dependent Salmonella-infecting bacteriophage, iEPS5. Appl Environ Microbiol. Phage abortive infection in lactococci: variations on a theme. Curr Opin Microbiol. Epigenetic control of Salmonella enterica O-antigen chain length: a tradeoff between virulence and bacteriophage resistance.
The phage tail tape measure protein, an inner membrane protein and a periplasmic chaperone play connected roles in the genome injection process of E. Mol Microbiol. Comptes rendus Acad Sci Paris. Davies J. Specialized microbial metabolites: functions and origins. J Antibiot Tokyo. Molecular and evolutionary determinants of bacteriophage host range.
Trends Microbiol. Pseudomonas predators: understanding and exploiting phage—host interactions. Nat Rev Microbiol. Lytic conversion of Escherichia coli by bacteriophage T5: blocking of the FhuA receptor protein by a lipoprotein expressed early during infection. Potent antibody-mediated neutralization limits bacteriophage treatment of a pulmonary Mycobacterium abscessus infection.
Nat Med. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Prophage-mediated defence against viral attack and viral counter-defence. Nat Microbiol. Systematic discovery of antiphage defense systems in the microbial pangenome. Doudna JA , Charpentier E. Structure and function of virion RNA polymerase of a crAss-like phage. Learning from bacteriophages: advantages and limitations of phage and phage-encoded protein applications.
Curr Protein Pept Sci. Molecular basis for lytic bacteriophage resistance in Enterococci. A widespread bacteriophage abortive infection system functions through a type IV toxin—antitoxin mechanism. Dybvig K. DNA rearrangements and phenotypic switching in prokaryotes.
Communication between viruses guides lysis—lysogeny decisions. Bacteriophage predation promotes serovar diversification in Listeria monocytogenes. Lippincott-Raven Publishers , Google Preview. Forde A , Fitzgerald GF. Molecular organization of exopolysaccharide EPS encoding genes on the lactococcal bacteriophage adsorption blocking plasmid, pCI Diverse enzymatic activities mediate antiviral immunity in prokaryotes. Phase variable expression of a single phage receptor in Campylobacter jejuni NCTC influences sensitivity toward several diverse CPS-dependent phages.
RNA Biol. BREX is a novel phage resistance system widespread in microbial genomes. EMBO J. Conformational changes leading to T7 DNA delivery upon interaction with the bacterial receptor. Bacteriophage-resistant Acinetobacter baumannii are resensitized to antimicrobials. Diversity-generating retroelements in phage and bacterial genomes. Microbiol Spectr. Restriction endonucleases: natural and directed evolution. Appl Microbiol Biotechnol.
Phage steering of antibiotic-resistance evolution in the bacterial pathogen, Pseudomonas aeruginosa. The arms race between bacteria and their phage foes. Reduction in exopolysaccharide viscosity as an aid to bacteriophage penetration through Pseudomonas aeruginosa biofilms. Dominant vibrio cholerae phage exhibits lysis inhibition sensitive to disruption by a defensive phage satellite. The Hin invertasome: protein-mediated joining of distant recombination sites at the enhancer.
The role of viperin in the innate antiviral response. In vivo genetic exchange of a functional domain from a type II A methylase between lactococcal plasmid pTR and a virulent bacteriophage. J Bacteriol. Hinton DM. Transcriptional control in the prereplicative phase of T4 development. Virol J. Hobbs Z , Abedon ST. Lancet Infect Dis. Genomic sequences of bacteriophages HK97 and HK pervasive genetic mosaicism in the lambdoid bacteriophages. Nat Commun. Only patients with P.
BPs or placebo was instilled in the ear canal and each patient was re-examined at days 7, 21, and 42 after treatment. Relative to baseline, clinical improvement was more common among treated patients. Moreover, the deterioration seen in some placebo-receiving subjects was not evidenced in patients given BP. The reduction in P. The mean recovery of BP in treated patients at the three study visits exceeded times the input dose.
No treatment-related adverse event was reported. A number of in vitro studies have suggested that BPs could be effective in treating cystic fibrosis CF patients. Essoh et al. It was shown that 33 out of 47 P. Saussereau et al. In both these studies, BP therapy overcame the obstacles of the CF environment, mainly the mucus characteristics and the biofilm inhibition European Commission, However, studies in humans are few and limited to case reports.
No randomized, placebo-controlled trial is presently available. Single cases of CF patients with chronic, otherwise untreatable, lung infection due to P. Moreover, aerosolized BPs were administered to 8 CF patients together with the conventional antibiotic treatment for 6—10 days.
Both P. However, definitive conclusions on the relevance of BP treatment in patients with CF cannot be drawn. Data regarding the use of BPs to treat bacterial disease in humans are few, sometimes conflicting or negative and almost always collected in trials that are not randomized and placebo controlled.
Moreover, the preparation of BPs for clinical use is difficult, and not all the problems strictly related with BP biology have been solved. Table 4 describes the main limitations associated with BP use. Identification of a therapeutic BP is very complicated. Isolation of BPs, generally from wastewater and sewage, is the first step and is per se relatively easy, although with differences between the various bacterial pathogens.
For example, it is significantly easier if P. However, before a BP is identified as a potential therapeutic agent, it has to be demonstrated that it is specific for a given bacterial strain. This is a relatively complicated problem, as evidence of lytic capacity of a BP can vary according to the interrelationships between the BP and bacterium and their modification with time together with the dose of virus used for the test.
Moreover, the BP genome must be sequenced and not contain integrase genes, as in the lysogenic type, antibiotic resistant genes ARG , genes for phage-encoded toxins or genes for other bacterial virulence factors. Finally, problems related to the formulation and stabilization of pharmaceutical preparations for clinical use are far from solved Vandenheuvel et al. In this regard, it has to be highlighted that studies seem to indicate that stability of preparations for clinical use is strictly BP dependent and stabilization strategies should be optimized for each BP separately Clark, ; Merabishvili et al.
This can lead to costly and time-consuming clinical trials that could discourage the pharmaceutical industry from starting research and production of preparations for human use. Emergence of bacterial resistance against BPs is potentially possible, as bacteria possess or can develop several mechanisms to prevent viral infections. Among these are hiding, change or loss of receptor, secretion of substances that prevent phage adhesion to the bacterial pathogen, activation of measures for blocking phage DNA injection into the cell and inhibition of phage replication and release Seed, Alteration or loss of receptor for membrane protein modifications has been demonstrated for E.
Secretion of extracellular polymeric substances and glycoconjugates has been described for Pseudomonas spp. Development of bacterial resistance to BPs can be reduced with the use of BP cocktails, with the administration of a higher initial BP inoculum or the association with antibiotics.
If BPs kill pathogens faster than they can replicate, a high inoculum is associated with a lower risk of development of BP-resistant bacteria. Lysogenic phages incorporate their DNA into the bacterial genome.
Consequently, they might be vehicles for horizontal exchange of genetic material and play a role in the diffusion of antibiotic resistance genes ARGs. However, the real contribution of phages to the diffusion of ARGs is not precisely defined. Most of the studies specifically planned to measure how often phages encode ARGs have suggested that these viruses are reservoirs of ARGs.
Moreover, diffusion of ARGs can be significantly favored by the presence in the environment of phage inducers, i. Treatment of wastewater samples with EDTA or sodium citrate activates the lytic cycle of lysogenic phages and leads to the generation of new phage particles, bacterial lyses, phage release outside the cell, and infection of a greater number of bacteria Colomer-Lluch et al.
Finally, great numbers of phages carrying genes associated with antibiotic resistance have been detected in secretions and tissues of patients who suffer from recurrent infections due to antibiotic resistant pathogens and had been previously repeatedly treated with antimicrobial drugs. One of the best examples in this regard is CF, as evidenced by the study conducted by Fancello et al.
This and similar findings led to the supposition that BPs might be vehicles for the adaptation of bacteria to the CF lung environment and for the emergence and selection of multidrug-resistant pathogens with chimeric repertoires Rolain et al.
However, a recent reevaluation of previously collected data has suggested that AGR abundance in phages was vastly overestimated and that the risk of transduction, although possible, is lower than previously thought. In several studies, conclusions were misled by the excessive bacterial DNA content of the studied samples.
Moreover, inadequate approaches to detect ARGs in phage genomes have been used Enault et al. Partially in agreement with these findings were Lekunberri et al.
The human-associated viromes did not carry or rarely carried ARGs, while those deriving from non-human sources harbored a significantly higher prevalence of ARGs. Bacteriophages and their products are non-self-antigens, and it is not surprising that they can be recognized by the immune system and induce responses that can theoretically reduce the benefit of BP administration.
Immune response to BPs has been demonstrated in both experimental animals and humans, although with differences according to the phage strain, the route of administration and the prior exposure. As phage titres remained stable in the B-cell-deficient mouse, the greatest part of phage clearance from blood seemed to be due to specific antibody production Srivastava et al.
However, even if not fully demonstrated, it seems likely that the immune response evoked by phages has a marginal or no impact on the potential bacterial killing of phage administration. Bacterial lysis occurs before a specific antibody is evoked. Moreover, with some exceptions, phage administration was generally not associated with tissue damage, an increase in pro-inflammatory cytokines or increased reactive oxygen species ROS production Park et al.
Miernikiewicz et al. Similar findings were reported by Hwang et al. Carmody et al. On the other hand, data collected in humans that seem to indicate that BP administration is safe seem to support that, even if present, the immune response to BPs is not clinically important. Use of BPs to overcome the problem of increasing microbial resistance to antibiotics is attractive, and some research data seem to indicate that it might be a rational measure.
To date, properly designed clinical trials specifically planned to evaluate BP efficacy are very few and partially negative. Moreover, the problem of how to prepare the formulations for standardized and clinical use in bacterial control, how to avoid or limit the risk of emergence of bacterial resistance and the transmission of genetic material are not completely solved problems.
In addition, the mechanisms concerning coevolution between BP and bacteria are unknown. NP and SE contributed to writing the manuscript. ES performed the literature review. All authors approved the final submitted version of the manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Abedon, S. Phage treatment of human infections. Bacteriophage 1, 66— Abul-Hassan, H. Bacteriophage therapy of Pseudomonas burn wound sepsis. Mediterr Burn Club 3, — Google Scholar. Alemayehu, D. Bogovazova, G. The efficacy of Klebsiella pneumoniae bacteriophage in the therapy of experimental Klebsiella infection. Immunobiological properties and therapeutic effectiveness of preparations from Klebsiella bacteriophages. PubMed Abstract Google Scholar. Bourdin, G.
Amplification and purification of T4-like Escherichia coli phages for phage therapy: from laboratory to pilot scale. Brabban, A. Evolution of foodborne pathogens via temperate bacteriophage-mediated gene transfer.
Foodborne Pathog. Carmody, L. Efficacy of bacteriophage therapy in a model of Burkholderia cenocepacia pulmonary infection.
Carvalho, C. The in vivo efficacy of two administration routes of a phage cocktail to reduce numbers of Campylobacter coli and Campylobacter jejuni in chickens.
BMC Microbiol. Chanishvili, N. Virus Res. Bacteriophages as therapeutic and prophylactic means: summary of the Soviet and Post Soviet experiences. Drug Deliv. Chibani-Chennoufi, S.
In vitro and in vivo bacteriolytic activities of Escherichia coli phages: implications for phage therapy. Agents Chemother. Clark, W. Comparison of several methods for preserving bacteriophages. Clokie, M. Phages in nature. Bacteriophage 1, 31— Colomer-Lluch, M. Quinolone resistance genes qnrA and qnrS in bacteriophage particles from wastewater samples and the effect of inducing agents on packaged antibiotic resistance genes.
Immunogenicity studies of proteins forming the T4 phage head surface. Bacteriophage as a treatment in acute medical and surgical infections. Domingo-Calap, P. Bacteriophages: protagonists of a post-antibiotic era. Antibiotics 7:E Drulis-Kawa, Z. Learning from bacteriophages - advantages and limitations of phage and phage-encoded protein applications.
Protein Pept. Edgar, R. Reversing bacterial resistance to antibiotics by phage-mediated delivery of dominant sensitive genes. Enault, F. Phages rarely encode antibiotic resistance genes: a cautionary tale for virome analyses. ISME J. Essoh, C.
The susceptibility of Pseudomonas aeruginosa strains from cystic fibrosis patients to bacteriophages. PLoS One 8:e European Commission Community Research and Development Information Service.
Phagoburn Report Summary. Fancello, L. Bacteriophages and diffusion of genes encoding antimicrobial resistance in cystic fibrosis sputum microbiota. Fauquet, C. Abbreviations for bacterial and fungal virus species names. Fish, R.
0コメント