Combinations of Lysostaphin with β-Lactams Are Synergistic against Oxacillin-Resistant
            <i>Staphylococcus epidermidis</i>

Kiri, Nandini; Archer, Gordon L.; Climo, Michael W.

doi:10.1128/aac.46.6.2017-2020.2002

Cited by 63 publications

(51 citation statements)

References 28 publications

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“…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].…”

Section: Introductionmentioning

confidence: 99%

Bactericidal synergy of lysostaphin in combination with antimicrobial peptides

Desbois

Coote

2011

Eur J Clin Microbiol Infect Dis

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Drug-resistant staphylococci are a serious problem that urgently requires the discovery of new therapeutic agents. There has been resurgence in interest for using lysostaphin (a specific anti-staphylococcal enzyme) as a treatment for infections caused by these important pathogens. However, bacterial resistance to lysostaphin is a problem but the use of a combination treatment may surmount this issue. In this present study, using viable counts from suspension incubations, lysostaphin is shown to be synergistically bactericidal in combination with various conventional antimicrobial peptides, the antimicrobial protein bovine lactoferrin, a lantibiotic (nisin), and certain lipopeptides used clinically (colistin, daptomycin and polymyxin B). Combinations that act in synergy are of clinical importance as these reduce the doses of the compounds needed for effective treatments and, most importantly, decrease the chances of resistance being selected. The use of lysostaphin in combination with a peptide may represent a new avenue to tackling drug-resistant staphylococci.

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Section: Introductionmentioning

confidence: 99%

Bactericidal synergy of lysostaphin in combination with antimicrobial peptides

Desbois

Coote

2011

Eur J Clin Microbiol Infect Dis

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“…S. aureus cell walls contain high proportions of pentaglycine, making lysostaphin a highly effective agent against both actively growing and quiescent bacteria. Lysostaphin has also been shown to be effective against S. epidermidis, albeit at higher concentrations of the enzyme (25,42). Lysostaphin has gained renewed interest as an antistaphylococcal therapeutic agent (12,24,30) because of the growing emergence of antibiotic-resistant S. aureus.…”

Section: Staphylococcal Infections Of Both Staphylococcus Aureus Andmentioning

confidence: 99%

Lysostaphin Disrupts Staphylococcus aureus and Staphylococcus epidermidis Biofilms on Artificial Surfaces

Wu¹,

Kusuma²,

Mond³

et al. 2003

Antimicrob Agents Chemother

267

169

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Staphylococci often form biofilms, sessile communities of microcolonies encased in an extracellular matrix that adhere to biomedical implants or damaged tissue. Infections associated with biofilms are difficult to treat, and it is estimated that sessile bacteria in biofilms are 1,000 to 1,500 times more resistant to antibiotics than their planktonic counterparts. This antibiotic resistance of biofilms often leads to the failure of conventional antibiotic therapy and necessitates the removal of infected devices. Lysostaphin is a glycylglycine endopeptidase which specifically cleaves the pentaglycine cross bridges found in the staphylococcal peptidoglycan. Lysostaphin kills Staphylococcus aureus within minutes (MIC at which 90% of the strains are inhibited [MIC 90 ], 0.001 to 0.064 g/ml) and is also effective against Staphylococcus epidermidis at higher concentrations (MIC 90 , 12.5 to 64 g/ml). The activity of lysostaphin against staphylococci present in biofilms compared to those of other antibiotics was, however, never explored. Surprisingly, lysostaphin not only killed S. aureus in biofilms but also disrupted the extracellular matrix of S. aureus biofilms in vitro on plastic and glass surfaces at concentrations as low as 1 g/ml. Scanning electron microscopy confirmed that lysostaphin eradicated both the sessile cells and the extracellular matrix of the biofilm. This disruption of S. aureus biofilms was specific for lysostaphin-sensitive S. aureus, as biofilms of lysostaphin-resistant S. aureus were not affected. High concentrations of oxacillin (400 g/ml), vancomycin (800 g/ml), and clindamycin (800 g/ml) had no effect on the established S. aureus biofilms in this system, even after 24 h. Higher concentrations of lysostaphin also disrupted S. epidermidis biofilms.

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“…Regarding gram-positive bacteria, there are examples of large proteins such as lysostaphin, an endopeptidase produced by Staphylococcus simulans, of interest for the treatment of infections caused by Staphylococcus spp. (19).…”

mentioning

confidence: 99%

The Antimicrobial Activity of Marinocine, Synthesized by Marinomonas mediterranea , Is Due to Hydrogen Peroxide Generated by Its Lysine Oxidase Activity

Lucas-Elı́o¹,

Gómez²,

Solano

et al. 2006

J Bacteriol

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Marinocine is a broad-spectrum antibacterial protein synthesized by the melanogenic marine bacterium Marinomonas mediterranea. This work describes the basis for the antibacterial activity of marinocine and the identification of the gene coding for this protein. The antibacterial activity is inhibited under anaerobic conditions and by the presence of catalase under aerobic conditions. Marinocine is active only in culture media containing L-lysine. In the presence of this amino acid, marinocine generates hydrogen peroxide, which causes cell death as confirmed by the increased sensitivity to marinocine of Escherichia coli strains mutated in catalase activity. The gene coding for this novel enzyme was cloned using degenerate PCR with primers designed based on conserved regions in the antimicrobial protein AlpP, synthesized by Pseudoalteromonas tunicata, and some hypothetical proteins. The gene coding for marinocine has been named lodA, standing for lysine oxidase, and it seems to form part of an operon with a second gene, lodB, that codes for a putative dehydrogenase flavoprotein. The identity of marinocine as LodA has been demonstrated by N-terminal sequencing of purified marinocine and generation of lodA mutants that lose their antimicrobial activity. This is the first report on a bacterial lysine oxidase activity and the first time that a gene encoding this activity has been cloned.

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Combinations of Lysostaphin with β-Lactams Are Synergistic against Oxacillin-Resistant Staphylococcus epidermidis

Cited by 63 publications

References 28 publications

Bactericidal synergy of lysostaphin in combination with antimicrobial peptides

Bactericidal synergy of lysostaphin in combination with antimicrobial peptides

Lysostaphin Disrupts Staphylococcus aureus and Staphylococcus epidermidis Biofilms on Artificial Surfaces

The Antimicrobial Activity of Marinocine, Synthesized by Marinomonas mediterranea , Is Due to Hydrogen Peroxide Generated by Its Lysine Oxidase Activity

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