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

Nina Schleimer1, Ursula Kaspar2, Dennis Knaack3

  • 1Institute of Medical Microbiology, University Hospital Münster (UKM), 48149 Münster, Germany. nina.schleimer@ukmuenster.de.

International Journal of Molecular Sciences
|February 10, 2019
PubMed

Insights

Recombinant bacteriophage endolysin HY-133 shows rapid bactericidal activity against methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), including small-colony variants. This endolysin offers a promising, fast-acting alternative for Staphylococcus aureus decolonization strategies.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Nasal carriage of Staphylococcus aureus (MSSA and MRSA) is a significant risk factor for infections.
  • Current decolonization and antibiotic treatments face challenges due to administration duration and emerging resistance, including functional resistance via small-colony variants (SCVs).

Purpose of the Study:

  • To evaluate the in vitro efficacy of the recombinant bacteriophage endolysin HY-133 against the small-colony variant (SCV) phenotype of Staphylococcus aureus.
  • To assess HY-133's activity against both methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains, including those with functional resistance.

Main Methods:

  • Minimal inhibitory (MIC) and minimal bactericidal concentrations (MBC) of HY-133 were determined for clinical SCVs, their isogenic wild types, and gentamicin-selected SCVs.
  • Time-kill studies were conducted to compare the bactericidal activity of HY-133 with oxacillin.

Main Results:

  • HY-133 demonstrated rapid bactericidal activity against all tested Staphylococcus aureus strains and phenotypes, with MIC and MBC values ranging from 0.12 to 1 mg/L.
  • HY-133 achieved a ≥3-log10 decrease in CFU/mL within 1 hour, significantly faster than oxacillin (4-24 hours).
  • The efficacy of HY-133 was independent of growth phase, resistance pattern, and SCV phenotype.

Conclusions:

  • Recombinant bacteriophage endolysin HY-133 exhibits potent and rapid in vitro bactericidal activity against Staphylococcus aureus, including SCV phenotypes.
  • HY-133's efficacy and independence from traditional resistance mechanisms make it a promising candidate for novel decolonization strategies against Staphylococcus aureus.
Keywords:
HY-133Staphylococcus aureusendolysinfunctional resistancenasal decolonizationoxacillinsmall-colony variantssusceptibility

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