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Open AccessArticle

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

1
Institute of Medical Microbiology, University Hospital Münster (UKM), 48149 Münster, Germany
2
HYpharm GmbH, 82347 Bernried, Germany
*
Author to whom correspondence should be addressed.
Present address: Ursula Kaspar, Landeszentrum Gesundheit Nordrhein-Westfalen, 44801 Bochum, Germany.
Present address: Dennis Knaack, St. Franziskus-Hospital GmbH, 48145 Münster, Germany.
§
Present address: Christof von Eiff, Pfizer Pharma GmbH, 10785 Berlin, Germany.
Int. J. Mol. Sci. 2019, 20(3), 716; https://doi.org/10.3390/ijms20030716
Received: 20 December 2018 / Revised: 1 February 2019 / Accepted: 2 February 2019 / Published: 7 February 2019
(This article belongs to the Special Issue Drug Resistance: Mechanisms and New Strategies)
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. View Full-Text
Keywords: Staphylococcus aureus; small-colony variants; oxacillin; endolysin; HY-133; susceptibility; nasal decolonization; functional resistance Staphylococcus aureus; small-colony variants; oxacillin; endolysin; HY-133; susceptibility; nasal decolonization; functional resistance
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Schleimer, N.; Kaspar, U.; Knaack, D.; von Eiff, C.; Molinaro, S.; Grallert, H.; Idelevich, E.A.; Becker, K. In Vitro Activity of the Bacteriophage Endolysin HY-133 against Staphylococcus aureus Small-Colony Variants and Their Corresponding Wild Types. Int. J. Mol. Sci. 2019, 20, 716.

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