Characterization of a Novel Bacteriophage Henu2 and Evaluation of the Synergistic Antibacterial Activity of Phage-Antibiotics

Li, Xianghui; Hu, Tongxin; Wei, Jiacun; He, Yuhua; Abdalla, Abualgasim Elgaili; Wang, Guoying; Li, Yanzhang; Teng, Tieshan

doi:10.3390/antibiotics10020174

Cited by 19 publications

(10 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was indicated that sublethal concentrations of linezolid, tetracycline and ketolide antibiotics can cause a 3-times increase in the plaque size of the S. aureus Myoviridae phage MR-5, whereas beta-lactam and quinolone antibiotics did not cause this effect [ 33 ]. An in vitro study demonstrated that a combination of a phage that infects S. aureus and antibiotics (clarithromycin, linezolid, cefotaxime, tetracycline and ciprofloxacin) increased the production of progeny phage [ 12 ].…”

Section: Possible Mechanisms Of Pasmentioning

confidence: 99%

“…The synergy of phages and antibiotics could also be due to a decrease in the MIC of antibiotics (e.g., amikacin, fosfomycin) [ 36 , 40 ]. Another study indicated the in vitro synergistic activity of the S. aureus Siphoviridae phage Henu2 with sub-lethal concentrations of antibiotics on the decrease of S. aureus more than three logs within 12 h [ 12 ]. Phage Henu 2 alone exhibited weak inhibitory activity on S. aureus growth.…”

Section: Possible Mechanisms Of Pasmentioning

confidence: 99%

“…Using fewer antibiotics in an era of rising multidrug-resistant bacteria in favor of new alternative treatments, such as phage therapy seems promising. Moreover, recent research suggested [ 10 – 12 ] that the combined use of antibiotics and phages may yield much better results in combating bacterial infections. Phage–antibiotic synergy (PAS) is described as the interaction between two factors when the combined effect in a bacterial reduction is greater than the sum of either substance alone [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far

et al. 2022

View full text Add to dashboard Cite

Bacteriophages (phages) may be used as an alternative to antibiotic therapy for combating infections caused by multidrug-resistant bacteria. In the last decades, there have been studies concerning the use of phages and antibiotics separately or in combination both in animal models as well as in humans. The phenomenon of phage–antibiotic synergy, in which antibiotics may induce the production of phages by bacterial hosts has been observed. The potential mechanisms of phage and antibiotic synergy was presented in this paper. Studies of a biofilm model showed that a combination of phages with antibiotics may increase removal of bacteria and sequential treatment, consisting of phage administration followed by an antibiotic, was most effective in eliminating biofilms. In vivo studies predominantly show the phenomenon of phage and antibiotic synergy. A few studies also describe antagonism or indifference between phages and antibiotics. Recent papers regarding the application of phages and antibiotics in patients with severe bacterial infections show the effectiveness of simultaneous treatment with both antimicrobials on the clinical outcome.

show abstract

Section: Possible Mechanisms Of Pasmentioning

confidence: 99%

Section: Possible Mechanisms Of Pasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In vitro studies performed on phage Henu2 showed that alone this phage exhibits unimpressive inhibitory action against S. aureus . However, in combination with oxides or antibiotics, the phage is capable of a 3-log reduction in bacterial load within 24 h ( Li et al, 2021 ). The ability of a phage to inhibit MRSA infection of skin wounds in a murine model was investigated by Ji et al (2020) .…”

Section: Phagesmentioning

confidence: 99%

Efficacy of Phage- and Bacteriocin-Based Therapies in Combatting Nosocomial MRSA Infections

Walsh

Johnson

Hill

et al. 2021

Front. Mol. Biosci.

View full text Add to dashboard Cite

Staphylococcus aureus is a pathogen commonly found in nosocomial environments where infections can easily spread - especially given the reduced immune response of patients and large overlap between personnel in charge of their care. Although antibiotics are available to treat nosocomial infections, the increased occurrence of antibiotic resistance has rendered many treatments ineffective. Such is the case for methicillin resistant S. aureus (MRSA), which has continued to be a threat to public health since its emergence. For this reason, alternative treatment technologies utilizing antimicrobials such as bacteriocins, bacteriophages (phages) and phage endolysins are being developed. These antimicrobials provide an advantage over antibiotics in that many have narrow inhibition spectra, enabling treatments to be selected based on the target (pathogenic) bacterium while allowing for survival of commensal bacteria and thus avoiding collateral damage to the microbiome. Bacterial resistance to these treatments occurs less frequently than with antibiotics, particularly in circumstances where combinatory antimicrobial therapies are used. Phage therapy has been well established in Eastern Europe as an effective treatment against bacterial infections. While there are no Randomized Clinical Trials (RCTs) to our knowledge examining phage treatment of S. aureus infections that have completed all trial phases, numerous clinical trials are underway, and several commercial phage preparations are currently available to treat S. aureus infections. Bacteriocins have primarily been used in the food industry for bio-preservation applications. However, the idea of repurposing bacteriocins for human health is an attractive one considering their efficacy against many bacterial pathogens. There are concerns about the ability of bacteriocins to survive the gastrointestinal tract given their proteinaceous nature, however, this obstacle may be overcome by altering the administration route of the therapy through encapsulation, or by bioengineering protease-resistant variants. Obstacles such as enzymatic digestion are less of an issue for topical/local administration, for example, application to the surface of the skin. Bacteriocins have also shown impressive synergistic effects when used in conjunction with other antimicrobials, including antibiotics, which may allow antibiotic-based therapies to be used more sparingly with less resistance development. This review provides an updated account of known bacteriocins, phages and phage endolysins which have demonstrated an impressive ability to kill S. aureus strains. In particular, examples of antimicrobials with the ability to target MRSA strains and their subsequent use in a clinical setting are outlined.

show abstract

“…It was thought at first that PAS effect is primarily dependent on the SOS response induced by these antibiotics (Comeau et al, 2007), but later investigations suggested the SOS response plays a minor role and that PAS is a result of alteration in cell morphology in response to the action of these antibiotics (Kim et al, 2018). PAS appears to be broadly applicable, spanning phages across the myoviridae (Chan et al, 2016;Comeau et al, 2007;Jansen et al, 2018;Kebriaei et al, 2020;Kirby, 2012;Liu et al, 2021;Malik et al, 2021;Ryan et al, 2012;Simon et al, 2021;Styles et al, 2020;Wang et al, 2020) siphoviridae (Knezevic et al, 2013;Li et al, 2021), and podoviridae families (Manohar et al, 2022;Save et al, 2022;Styles et al, 2020;Torres-Barceló et al, 2014Verma et al, 2009). In addition to phages, PAS has been demonstrated in many hosts: Klebsiella pneumoniae (Bedi et al, 2009;Pacios et al, 2021;, Pseudomonas aeruginosa (Chan et al, 2016;Chaudhry et al, 2017;Coulter et al, 2014;Duplessis et al, 2021;Engeman et al, 2021;Hagens et al, 2006;Oechslin et al, 2017), Actinobacter baumannii (Styles et al, 2020), Staphylococcus aureus (Chhibber et al, 2013;Dickey et al, 2019;Iqbal et al, 2020;Kaur and Chhibber, 2021;Kebriaei et al, 2020;Van Nieuwenhuyse et al, 2021;…”

Section: Introductionmentioning

confidence: 99%

Temperate phage-antibiotic synergy across antibiotic classes reveals new mechanism for preventing lysogeny

Al-Anany

Hynes

2022

Preprint

View full text Add to dashboard Cite

A recent demonstration of potent synergy between a temperate phage and the antibiotic ciprofloxacin suggested a scalable approach to exploiting temperate phages in therapy, termed temperate phage-antibiotic synergy (tPAS), which specifically interacted with the lysis-lysogeny decision. To determine whether this would hold true more broadly across antibiotics, we challenged Escherichia coli K12 with the well-studied model λ-like phage HK97 and a set of 13 antibiotics spanning seven classes. As expected, given the conserved induction pathway targeted, we observed synergy with classes of drugs known to induce an SOS response; a sulfa drug, other quinolones, Mitomycin C, and some β-lactams. Curiously, we observed an equally potent synergy with antibiotics not known to induce the SOS response: protein synthesis inhibitors gentamicin, kanamycin, tetracycline, and azithromycin. The synergy results in an 8-fold reduction in the effective MIC of gentamicin, complete eradication of the bacteria, and, when deliberately administered at sub-optimal doses, drastically decreases the frequency of lysogens emerging from the combined challenge – more so even than was previously described for ciprofloxacin. However, unlike ciprofloxacin, lysogens exhibit no increased sensitivity to the antibiotic, synergy was maintained in the absence of RecA, and, when quantified over time, the antibiotic reduced the initial frequency of lysogeny rather than result in selection against formed lysogens. Not only do our results confirm that SOS-inducing antibiotics broadly result in temperate-phage specific synergy, but we other antibiotics can interact with temperate phages specifically and result in potent synergy. This is the first report of a means of chemically blocking entry into lysogeny, providing a new means for manipulating the key lysis-lysogeny decision point in temperate phages.

show abstract

Characterization of a Novel Bacteriophage Henu2 and Evaluation of the Synergistic Antibacterial Activity of Phage-Antibiotics

Cited by 19 publications

References 76 publications

Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far

Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far

Efficacy of Phage- and Bacteriocin-Based Therapies in Combatting Nosocomial MRSA Infections

Temperate phage-antibiotic synergy across antibiotic classes reveals new mechanism for preventing lysogeny

Contact Info

Product

Resources

About