High-level potentiation of lysostaphin anti-staphylococcal activity by lysozyme

Abstract

The purpose of this study was to determine whether lysostaphin would enhance its anti-staphylococcal efficacy in combination with lysozyme. Minimum inhibitory concentrations (MICs) of lysostaphin and lysozyme were separately determined for 41 strains belonging to 10 different species of human staphylococci. Lysozyme was virtually inactive and showed MICs of 15 mg/ml. On the contrary, all strains were susceptible to lysostaphin and showed MICs ranging from 2.5 to 60 jig/ml for the different Staphylococcus species. When the MIC of lysostaphin was determined in media containing submultiples of the MIC of lysozyme, the values obtained were much lower. The reduction of the lysostaphin MIC ranged from 16-to 200-fold in the different species tested. In Staphylococcus aureus, in particular, the combination of lysostaphin with 1.5 mg of lysozyme per ml reduced the MIC of lysostaphin by 25-fold. The activities of two combinations of the two enzymes were evaluated: one combination was expected to be active on S. aureus only, and the other combination was expected to inhibit all Staphylococcus strains. The first combination (0.5 ,ug of lysostaphin plus 0.5 mg of lysozyme per ml) was inhibitory to all of the 84 S. aureus strains tested, whereas 137 of 151 strains of other Staphylococcus species were unaffected. On the contrary, all of the 235 Staphylococcus strains tested were inhibited by the second combination (4

Differentially conserved staphylococcal SH3b_5 cell wall binding domains confer increased staphylolytic and streptolytic activity to a streptococcal prophage endolysin domain

“…However, there are numerous reports of C-terminally deleted lysins where the N-terminal lytic domain maintains staphylococcal- (Donovan et al, 2006c) or streptococcal-specificity (Donovan et al, 2006a;Donovan et al, 2006b) in the absence of its SH3b domain. Also, at high enough concentrations, even lysostaphin will digest the peptidoglycan of staphylococcal species other than S. aureus (Cisani et al, 1982).…”

Bactericidal synergy of lysostaphin in combination with antimicrobial peptides

“…Nonetheless, one drawback with lysostaphin is the high preponderance for bacterial resistance to be selected through mutations in lyrA or the fem operon [12][13][14]. However, therapies that contain multiple antimicrobial agents can reduce the opportunity for resistance to be selected and various lysostaphin-containing combination treatments have been investigated, including lysostaphin with: i) various antibacterial drugs used clinically [7,8,13,[15][16][17][18][19][20]; ii) tea tree oil [8]; iii) lysozyme [21]; iv) the phage lytic enzyme LysK [22]; and v) certain conventional antimicrobial peptides (AMPs) [10,15,19,23]. The incorporation of an AMP into a combination therapy further reduces the opportunity for bacterial resistance, as these compounds typically disrupt the bacterial cell membrane and resistance to AMPs is reported only rarely [24][25][26][27].…”

Cloning, sequence, and expression of the lysostaphin gene from Staphylococcus simulans.

“…The enzyme lyses practically all known staphylococcal species but it is inactive against bacteria of all other genera (1,3,4). Although its catalytic properties are not well-characterized, lysostaphin apparently hydrolyzes polyglycine cross-links present in the peptidoglycan of the staphylococcal cell wall (5).…”