Phage lysins |
Streptococcus pneumoniae
|
Pal amidase from pneumococcal phage Dp-1 |
Mouse model of nasopharyngeal colonization |
Topical nasal and pharyngeal administration |
Single dose of 1400 U or 700 U |
Bacteria eradication |
(Loeffler et al. 2001) |
Cpl-1 lysozyme from pneumococcal phage Cp-1 |
Mouse model of bacteremia and nasopharyngeal colonization |
Intravenous injection and topical nasal administration |
Single dose of 2000 μg |
Bacterial eradication; 80% of animals protected from death |
(Loeffler et al. 2003) |
Rat model of pneumococcal endocarditis and bacteremia |
Intravenous injection |
10 mg/kg, followed by a continuous infusion of 5 mg/kg/h for 6 h or 250 mg/kg, followed by continuous infusion of 250 mg/kg/h for 6 h |
Bacteria eradication obtained with a high dose (250 mg/kg) |
(Entenza et al. 2005) |
Non-invasive mouse model of nasal mucosa infection |
Topical intranasal administration |
Two doses of 1000 μg |
Bacteria eradication in 90% of animals; 100% prevention of acute otitis media |
(McCullers et al. 2007) |
Rat model of meningitis |
Intracisternal injection |
Single dose of 20 mg/kg for intracisternal injection and 200 mg/kg for intraperitoneal administration |
Bacterial cfu reduction of 3 orders (intracisternal injection) and 2 orders (intraperitoneal administration) |
(Grandgirard et al. 2008) |
Mouse model of pneumococcal pneumonia and nasopharyngeal colonization |
Intraperitoneal injection and topical intranasal administration |
Multidose treatment of 1 mg |
100% of animals protected from death |
(Witzenrath et al. 2009) |
Mouse model of pneumococcal pneumonia and nasopharyngeal colonization |
Inhalation of aerosolized Cpl-1 |
Aerosolized single dose of 25 μL |
80% of animals protected from death |
(Doehn et al. 2013) |
Pal and Cpl-1 |
Mouse model of sepsis |
Intraperitoneal injection |
Single dose of 200 μg; 1100 U of both enzymes |
Bacteria eradication |
(Jado et al. 2003) |
Cpl-711 chimeric lysozyme |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 25–500 μg |
100% of animals protected from death |
(Díez-Martínez et al. 2014) |
Streptococcus pyogenes
|
PlyC amidase, peptidase from streptococcal phage C1 |
Mouse model of nasopharyngeal colonization |
Topical oral and nasal administration |
Single dose of different amount of enzyme (250–1000 U) |
Bacteria eradication; 100% prevention against streptococcal colonization |
(Nelson et al. 2001) |
Streptococcus pyogenes
|
PlyPy peptidase from S. pyogenes MGAS5005 prophage |
Mouse model of bacteremia |
Intraperitoneal injection |
Two doses of 1 mg |
Bacterial cfu reduction of 2 orders; 50% of animals protected from death |
(Lood et al. 2014) |
Streptococcus agalactiae
|
PlyGBS peptidase, lysozyme from streptococcal phage NCTC 11261 |
Mouse model of vaginal infection and oropharynx colonization |
Topical intravaginal, oral and intranasal administration |
Single dose of 10 U |
Bacterial cfu reduction of 3 orders (vaginal infection) and 2 orders (oropharynx colonization) |
(Cheng et al. 2005) |
PlyGBS90–1 peptidase, lysozyme (modified PlyGBS) |
Mouse model of vaginal infection |
Topical intravaginal administration |
Single dose of 30 nmol |
Bacterial cfu reduction of 4 orders |
(Cheng and Fischetti 2007) |
Streptococcus pyogenes and Staphylococcus aureus MRSA Streptococcus suis
|
PlySs2 amidase, peptidase from S. suis 89/1591 prophage |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 2 mg |
94% and 89% of animals protected from death for S. pyogenes and MRSA, respectively |
(Gilmer et al. 2013) |
Mouse model of nasal mucosa infection |
Topical intranasal administration |
Single dose of 0,1 mg |
Bacterial cfu reduction of > 4 orders |
(Gilmer et al. 2017) |
Staphylococcus aureus MRSA |
MV-L amidase, peptidase from staphylococcal phage phiMR11 |
Mouse model of nasal infection and bacteremia |
Topical intranasal administration and intraperitoneal injection |
Single dose of 310–500 U |
100% of animals protected from death |
(Rashel et al. 2007) |
ClyS chimeric amidase, peptidase |
Mouse model of nasal infection and bacteremia |
Topical intranasal administration and intraperitoneal injection |
Single dose of 960 μg in nasal model; single dose of 2 mg in systemic model |
Bacterial cfu reduction of 2 orders (nasal model); 88% of animals protected from death (systemic model) |
(Daniel et al. 2010) |
Mouse model of skin infection |
Topical skin application |
Single dose of 1%, 6%, or 10% (wt/wt) |
Bacterial cfu reduction of 3 orders (10% dose) |
(Pastagia et al. 2011) |
LysGH15 amidase, peptidase from staphylococcal phage, GH15 |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 5–100 μg |
Bacteria eradication; 100% of animals protected from death for ≥50 μg dose |
(Gu et al. 2011a) |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 50 μg |
Bacteria eradication |
(Gu et al. 2011b) |
Mouse model of bacteremia |
Intravenous injection |
Single dose of 50 μg |
Bacterial cfu reduction of 4 orders; 100% of animals protected from death |
(Zhang et al. 2016) |
P-27/HP endolysin (unknown mode of action) from staphylococcal phage P-27/HP |
Mouse model of bacteremia and healthy mice (safety test) |
Intraperitoneal injection (for model of bacteremia) and intramuscular, subcutaneous, intravenous, and intraperitoneal injections for safety test on healthy mice |
Single dose of 250 μg |
Bacterial cfu reduction of 3 orders |
(Gupta and Prasad 2011b) |
P128 chimeric VAL amidase, peptidase |
Rat model of nasal infection |
Topical intranasal administration |
Single dose of 100 μg |
Bacterial cfu reduction of ≥ 3 orders |
(Paul et al. 2011) |
λSA2-E-Lyso-SH3b chimeric peptidase |
Mouse model of mastitis |
Intramammary infusion |
Single dose of 25 μg |
Bacterial cfu reduction of 0.63–0.81 orders |
(Schmelcher et al. 2012b) |
Ply187AN-KSH3b chimeric peptidase |
Mouse model of endophthalmitis |
Intravitreal injection |
Single dose of 1 μg/eye |
Bacterial cfu reduction of 1 order; significant effects in protecting eyes from endophthalmitis |
(Singh et al. 2014) |
80αLyt2 amidase, peptidase from staphylococcal phage phi80α |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 200 μg |
100% of animals protected from death |
(Schmelcher et al. 2014) |
phi11 amidase, peptidase from staphylococcal phage phi11 |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 200 μg |
100% of animals protected from death |
(Schmelcher et al. 2014) |
LysK amidase, peptidase from staphylococcal phage K |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 200 μg |
100% of animals protected from death |
(Schmelcher et al. 2014) |
2638A amidase, peptidase from S. aureus 2854 prophage |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 200 μg |
100% of animals protected from death |
(Schmelcher et al. 2014) |
LysWMY amidase, peptidase from staphylococcal phage phiWMY |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 200 μg |
100% of animals protected from death |
(Schmelcher et al. 2014) |
PlyTW amidase, peptidase from staphylococcal phage Twort |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 200 μg |
50% of animals protected from death |
(Schmelcher et al. 2014) |
phiSH2 amidase, peptidase from S. haemolyticus prophage phiSH2 |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of 200 μg |
50% of animals protected from death |
(Schmelcher et al. 2014) |
P68 amidase, peptidase from staphylococcal phage phiP68 |
Mouse model of bacteremia |
Intraperitoneal injection |
Single dose of ∼ 120 μg |
No protecting effect (low solubility) |
(Schmelcher et al. 2014) |
SAL-1 amidase, peptidase from the staphylococcal phage SAP-1 |
Mouse model of bacteremia |
Intravenous injection |
Two doses of 12.5–25 mg/kg |
Bacteria eradication |
(Jun et al. 2013) |
Healthy rats and dogs (safety test) |
Intravenous injection |
Multiple doses of 25–100 mg/kg |
No serious adverse symptoms observed |
(Jun et al. 2014) |
Healthy monkeys (safety test) |
Intravenous injection |
Multiple doses of 1–80 mg/kg |
No serious adverse symptoms observed |
(Jun et al. 2016) |
Clinical trial on healthy male volunteers (safety test) |
Intravenous injection |
Single and escalating dose of 0.1–10 mg/kg |
No serious adverse symptoms observed |
(Jun et al. 2017) |
Bacillus anthracis
|
PlyG amidase from B. anthracis gamma phage |
Mouse model of peritonitis and bacteremia |
Intravitreal injection |
Single dose of 50–150 U |
~ 70% of animals protected from death |
(Schuch et al. 2002) |
PlyPH amidase from B. Anthracis prophage |
Mouse model of peritonitis and bacteremia |
Intraperitoneal injection |
Single dose of 1.2 mg/ml |
40% of animals protected from death |
(Yoong et al. 2006) |
Acinetobacter baumannii
|
PlyF307 lysozyme from Acinetobacter phage RL-2015 |
Mouse model of bacteremia and mouse in vivo catheter model |
Intraperitoneal injection and topical injection directly into the catheter under the skin |
Single dose of 1 mg for intraperitoneal injection and two doses of 1 mg for topical application |
50% of animals protected from death; catheter biofilm reduction |
(Lood et al. 2015) |
Pseudomonas aeruginosa
|
Artilysin® (PVP-SE1gp146 lysozyme combining a polycationic nonapeptide) |
Model of Caenorhabditis elegans gut infection |
Oral and topical administration |
20 μg/ml per well (~ 10 nematodes per well) |
40–63% of animals protected from death (in the presence of 0.5 mM EDTA) |
(Briers et al. 2014) |
Phage depolymerases |
Escherichia coli K1 |
EndoE endosialidase from coliphage E |
Neonatal rat model of bacteremia |
Intraperitoneal injection |
Single dose of 20 μg |
100% of animals protected from death |
(Mushtaq et al. 2004) |
Neonatal rat model of bacteremia |
Intraperitoneal injection |
Single dose of 0.25 μg |
80% of animals protected from death |
(Mushtaq et al. 2004) |
Salmonella Typhimurium |
P22sTsp endorhamnosidase from Salmonella phage P22 |
Chicken model of gastrointestinal infection |
Oral administration |
Multiple doses of 30 μg |
Bacterial cfu reduction of ~ 1 order |
(Waseh et al. 2010) |
Klebsiella pneumoniae
|
K64dep capsule depolymerase from Klebsiella phage K64-1 |
Mouse model of bacteremia |
Intraperitoneal injection |
Multiple doses of 18.75–150 μg |
100% of animals protected from death |
(Pan et al. 2015) |
depoKP36 capsule depolymerase from Klebsiella phage KP36 |
Galleria mellonella infection model |
Injection into the last pro-leg |
Single dose of 280 μg/ml |
40% of animals protected from death |
(Majkowska-Skrobek et al. 2016) |
Pseudomonas aeruginosa
|
LKA1gp49 LPS lyase from Pseudomonas phage LKA1 |
Galleria mellonella infection model |
Injection into the last pro-leg |
Single dose of 0.05–0.5 μg |
20% of animals protected from death |
(Olszak et al. 2017) |