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

Abstract

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.

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

“…Endolysins also exhibit properties that can be very useful for the treatment of chronic infections. For instance, there is in vitro evidence of the efficacy of some endolysins against small colony variants (SCVs) of clinical origin, such as endolysin HY-133 [55], or against persister cells, such as LysH5 [27]. It is important to note that some endolysins have a synergistic effect with antibiotics, which might help to boost their efficacy against chronic infections.…”

Bactericidal Activity of Sodium Bituminosulfonate against Staphylococcus aureus

“…To the best of our knowledge, no data are available on the rapidity of the bactericidal effect of sodium bituminosulfonate. Therefore, we characterized the bactericidal effect of sodium bituminosulfonate using a time-kill methodology [ 29 , 30 ]. In this first study of sodium bituminosulfonate’s bactericidity, a very rapid bactericidal effect against MSSA and MRSA was observed, with 99.9% of the inoculum already killed after a short incubation time of 30 min by concentrations corresponding to 16× MIC and 256× MIC ( Figure 1 ).…”

Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application

“…They can be easily identified and prepared as pure recombinant proteins and have proven to be efficient in killing bacteria, including multi-drug-resistant variants [ 231 , 232 , 233 , 234 ]. They are rapid-acting [ 166 , 202 , 235 , 236 , 237 , 238 , 239 ] and stable over a range of pHs and temperatures [ 182 , 240 , 241 ]. PGHs also selectively target specific species of bacteria without harming commensal microflora [ 61 , 242 , 243 ].…”