Bactericidal activity of bacteriophage endolysin HY-133 against Staphylococcus aureus in comparison to other antibiotics as determined by minimum bactericidal concentrations and time-kill analysis

Knaack, Dennis; Idelevich, Evgeny A.; Schleimer, Nina; Molinaro, Sonja; Kriegeskorte, André; Peters, Georg; Becker, Karsten

doi:10.1016/j.diagmicrobio.2018.11.005

Cited by 20 publications

(16 citation statements)

References 36 publications

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“…Along the same lines, the data presented here indicates that all clinical MRSA isolates were susceptible to LysRODI, although to different degrees. Similarly, the recombinant endolysin HY-133 was highly active against all tested MSSA and MRSA isolates, including isolates resistant to mupirocin, ceftaroline/ceftobiprole and borderline oxacillin [46,47]. To further examine the impact of endolysin treatment, the strains were clustered into three susceptibility groups (low, average and high), the high susceptibility group being the least numerous.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Clinical MRSA Isolates from Northern Spain and Assessment of Their Susceptibility to Phage-Derived Antimicrobials

et al. 2020

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Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent nosocomial pathogen, causing a wide range of diseases. The increased frequency of MRSA isolates in hospitals and the emergence of vancomycin resistance have sparked the search for new control strategies. This study aimed to characterize sixty-seven MRSA isolates collected from both infected patients and asymptomatic carriers in a Spanish hospital. RAPD-PCR allowed the identification of six genetic patterns. We also investigated the presence of genes involved in producing adhesins, toxins and the capsule; the biofilm; and antimicrobial resistance. A notable percentage of the isolates carried virulence genes and showed medium-high ability to form biofilms. Next, we assessed the strains’ susceptibility to two phages (phiIPLA-C1C and phiIPLA-RODI) and one endolysin (LysRODI). All strains were resistant to phiIPLA-C1C, and most (70.2%) were susceptible to phiIPLA-RODI. Regarding LysRODI, all strains displayed susceptibility, although to varying degrees. There was a correlation between endolysin susceptibility and the random amplification of polymorphic DNA (RAPD) profile or the presence of some virulence genes (fnbA, eta, etb, PVL and czr), but that was not observed with biofilm-forming ability, strain origin or phage sensitivity. Taken together, these findings can help to explain the factors influencing endolysin effectiveness, which will contribute to the development of efficient therapies targeting MRSA infections.

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Section: Discussionmentioning

confidence: 99%

Characterization of Clinical MRSA Isolates from Northern Spain and Assessment of Their Susceptibility to Phage-Derived Antimicrobials

et al. 2020

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“…The minimum inhibitory concentration (MIC) test systems were created by diluting different drug solution in 96-well plates to a volume of 100 μL, and the enrofloxacin sodium, enrofloxacin hydrochloride and EM were double diluted 28 to final concentrations ranging from 25 to 0.0488 μg/mL, and then 100 μL bacterial suspensions was added to each drug-containing well. The MIC was determined visually as the first dilution step with a complete growth inhibition [30][31][32] and the minimum bactericidal concentration (MBC) was determined after the MIC. 10 μL mixtures were extracted from the wells in the 96-well plate that were visually free of bacterial growth, and then uniformly coated on the MHA medium after serial dilution, and incubated at 37°C for 18-24 h. The number of colonies on the plate was calculated, and the minimum concentration killing 99.9% of the bacteria was recorded as MBC.…”

Section: The Antibacterial Activity In Vitromentioning

confidence: 99%

“…10 μL mixtures were extracted from the wells in the 96-well plate that were visually free of bacterial growth, and then uniformly coated on the MHA medium after serial dilution, and incubated at 37°C for 18-24 h. The number of colonies on the plate was calculated, and the minimum concentration killing 99.9% of the bacteria was recorded as MBC. [30][31][32] The MIC and MBC of standard strains and clinical strains of Escherichia coli, Salmonella and Staphylococcus aureus were determined.…”

Section: The Antibacterial Activity In Vitromentioning

confidence: 99%

<p>Synthesis, Characterization, and Pharmacodynamics Study of Enrofloxacin Mesylate</p>

Pei

Yang

et al. 2020

DDDT

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Introduction: Enrofloxacin is used in the treatment of a wide variety of bacterial infections in mammals. However, its poor solubility limits the clinical use. Methods: In order to improve the solubility of enrofloxacin, the enrofloxacin mesylate (EM) were obtained by a chemical synthesis method. The characterization of EM was carried out using ultraviolet scan (UV), synchronous thermal analysis (SDT), fourier transform infrared spectrometer (FTIR) and mass spectrometry (MS), nuclear magnetic resonance (NMR) and X-ray powder diffraction analysis (XRPD). Acute toxicity of EM in Kunming mice was studied. Besides, pharmacokinetic studies were performed in New Zealand rabbits at a single oral dose of 10 mg/kg, and the antibacterial activity of EM was also evaluated. Results: EM was successfully synthesized and purified. The stoichiometric ratio of mesylate to enrofloxacin was 1:1 and the aqueous solubility of EM was 483.01±4.06 mg/mL, the solubility of EM was about 2000 times higher than enrofloxacin. The oral lethal dose (LD 50 ) of EM was 1168.364 mg/kg, and the pharmacokinetics indicated that the oral relative bioavailability of EM was about 1.79 times and 1.48 times higher than that of enrofloxacin and enrofloxacin hydrochloride, respectively. In addition, the in vitro antibacterial activity of EM was not significantly changed compared with enrofloxacin and enrofloxacin hydrochloride. Conclusion: EM has higher solubility, low toxicity for oral use, and increases the oral bioavailability in rabbit. This study may be of benefit for the development of new enrofloxacin drugs.

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“…[52,53,54,55], and Staphylococcus spp. [56,57,58,59,60,61,62]. Moreover, phage endolysins were shown to be active against difficult-to-treat bacterial infections caused by phenotypically resistant bacterial populations, e.g., by being embedded in biofilms [63,64,65].…”

Section: Introductionmentioning

confidence: 99%

“…Within the peptidoglycan of S. aureus , this CHAP domain cleaves between d -alanine at the termini of the tetrapeptide and glycine of the pentaglycine crossbridge, and is thereby responsible for the lytic mode of action [67]. HY-133 was previously shown to be highly active against methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA isolates [59,60,61,62]. However, the efficacy of Hy-133 against SCVs has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Activity of the Bacteriophage Endolysin HY-133 against Staphylococcus aureus Small-Colony Variants and Their Corresponding Wild Types

Schleimer

Kaspar

Knaack

et al. 2019

IJMS

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Nasal carriage of methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) represents both a source and a risk factor for subsequent infections. However, existing MRSA decolonization strategies and antibiotic treatment options are hampered by the duration of administration and particularly by the emergence of resistance. Moreover, beyond classical resistance mechanisms, functional resistance as the formation of the small-colony variant (SCV) phenotype may also impair the course and treatment of S. aureus infections. For the recombinant bacteriophage endolysin HY-133, rapid bactericidal and highly selective in vitro activities against MSSA and MRSA has been shown. In order to assess the in vitro efficacy of HY-133 against the SCV phenotype, minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) were evaluated on clinical SCVs, their isogenic wild types, as well as on genetically derived and gentamicin-selected SCVs. For all strains and growth phases, HY-133 MIC and MBC ranged between 0.12 and 1 mg/L. Time-kill studies revealed a fast-acting bactericidal activity of HY-133 resulting in a ≥3 − log10 decrease in CFU/mL within 1 h compared to oxacillin, which required 4–24 h. Since the mode of action of HY-133 was independent of growth phase, resistance pattern, and phenotype, it is a promising candidate for future S. aureus decolonization strategies comprising rapid activity against phenotypic variants exhibiting functional resistance.

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Bactericidal activity of bacteriophage endolysin HY-133 against Staphylococcus aureus in comparison to other antibiotics as determined by minimum bactericidal concentrations and time-kill analysis

Cited by 20 publications

References 36 publications

Characterization of Clinical MRSA Isolates from Northern Spain and Assessment of Their Susceptibility to Phage-Derived Antimicrobials

Characterization of Clinical MRSA Isolates from Northern Spain and Assessment of Their Susceptibility to Phage-Derived Antimicrobials

<p>Synthesis, Characterization, and Pharmacodynamics Study of Enrofloxacin Mesylate</p>

In Vitro Activity of the Bacteriophage Endolysin HY-133 against Staphylococcus aureus Small-Colony Variants and Their Corresponding Wild Types

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