The Novel Phage-Derived Antimicrobial Agent HY-133 Is Active against Livestock-Associated Methicillin-Resistant Staphylococcus aureus

Kaspar, Ursula; Sautto, Jorge A. de Haro; Molinaro, Sonja; Peters, Georg; Idelevich, Evgeny A.; Becker, Karsten

doi:10.1128/aac.00385-18

Cited by 4 publications

(6 citation statements)

References 41 publications

(55 reference statements)

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“…We previously demonstrated the very fast and high bactericidal in vitro activity of the recombinant endolysin HY-133 against several clinical MSSA and (LA-)MRSA isolates [59,60,61,62]. To further investigate the activity of HY-133, it was challenged with 12 clinical S. aureus strain pairs, each comprising WT and stable SCV phenotypes.…”

Section: Resultsmentioning

confidence: 99%

“…[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%

“…The recombinant endolysin HY-133 (HYpharm GmbH, Bernried, Germany) used in this study represents a stability-optimized derivative of endolysin PRF-119 [59,60]. The modular structure of HY-133 comprises a CBD from lysostaphin, responsible for the specific attachment to the peptidoglycan of S. aureus [59,62]. Its EAD consists of the cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) originating from the recombinant endolysin LysK of phage K [62,66].…”

Section: Introductionmentioning

confidence: 99%

“…The modular structure of HY-133 comprises a CBD from lysostaphin, responsible for the specific attachment to the peptidoglycan of S. aureus [59,62]. Its EAD consists of the cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) originating from the recombinant endolysin LysK of phage K [62,66]. 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].…”

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%

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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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