9 research outputs found
Antimicrobial Activity and 70S Ribosome Binding of Apidaecin-Derived Api805 with Increased Bacterial Uptake Rate
In view of the global spread of multiresistant bacteria and the occurrence of panresistant
bacteria, there is an urgent need for antimicrobials with novel modes of action. A promising class is
antimicrobial peptides (AMPs), including them proline-rich AMPs (PrAMPs), which target the 70S
ribosome to inhibit protein translation. Here, we present a new designer peptide, Api805, combining
the N- and C-terminal sequences of PrAMPs Api137 and drosocin, respectively. Api805 was similarly
active against two Escherichia coli B strains but was inactive against E. coli K12 strain BW25113. These
different activities could not be explained by the dissociation constants measured for 70S ribosome
preparations from E. coli K12 and B strains. Mutations in the SbmA transporter that PrAMPs use to
pass the inner membrane or proteolytic degradation of Api805 by lysate proteases could not explain
this either. Interestingly, Api805 seems not to bind to the known binding sites of PrAMPs at the
70S ribosome and inhibited in vitro protein translation, independent of release factors, most likely
using a “multimodal effect”. Interestingly, Api805 entered the E. coli B strain Rosetta faster and at
larger quantities than the E. coli K-12 strain BW25113, which may be related to the different LPS core
structure. In conclusion, slight structural changes in PrAMPs significantly altered their binding sites
and mechanisms of action, allowing for the design of different antibiotic classes
FORMULATIONS AND TECHNOLOGIES IN GROWTH HORMONE DELIVERY
Growth hormone treatment has many indications including the treatment of growth hormone deficiency, Prader–Willi syndrome, chronic renal insufficiency, Turner syndrome, AIDS-related wasting, idiopathic short stature in children, and accumulation of fat which related in adults with lipodystrophy. Conventional therapy was achieved using intramuscular and subcutaneous injections. However, noncompliance was very high. To solve this; many studies have been attempted to prepare long-acting formulations and new to make derivatives of growth hormone and to use alternative routes of administration which term as noninvasive routes such as intranasal, pulmonary, transdermal and oral. New delivery systems were also used such as needle-free and auto-injector devices. In this review, different formulations, technologies, and routes of growth hormone delivery will be presented with the discussion of the principles of formulations and selected additives that were used to achieve improved growth hormone formulations
Antimicrobial and Antibiofilm Activity of UP-5, an Ultrashort Antimicrobial Peptide Designed Using Only Arginine and Biphenylalanine
The recent upsurge of multidrug resistant bacteria (MDRB) among global communities has
become one of the most serious challenges facing health professionals and the human population
worldwide. Cationic ultrashort antimicrobial peptides (USAMPs) are a promising group of molecules
that meet the required criteria of novel antimicrobial drug development. UP-5, a novel penta-peptide,
displayed significant antimicrobial activities against various standard and clinical isolates of MDRB.
UP-5 displayed MICs values within the range of (10–15 M) and (55–65 M) against Gram-positive
and Gram-negative bacteria, respectively. Furthermore, UP-5 displayed antibiofilm activity with
minimum biofilm eradication concentration (MBEC) value as equal to twofold higher than MIC value.
At the same inhibitory concentrations, UP-5 exhibited very low or negligible toxicity toward human
erythrocytes and mammalian cells. Combining UP-5 with conventional antibiotics led to a synergistic
or additive mode of action that resulted in the reduction of the MIC values for some of the antibiotics
by 99.7% along a significant drop in MIC values of the peptide. The stability profile of UP-5 was
evaluated in full mouse plasma and serum with results indicating a more stable pattern in plasma.
The present study indicates that USAMPs are promising antimicrobial agents that can avoid the
negative characteristics of conventional antimicrobial peptides. Additionally, USAMPs exhibit good
to moderate activity against MDRB, negligible toxicity, and synergistic outcomes in combination with
conventional antimicrobial agents
Antimicrobial Activity and 70S Ribosome Binding of Apidaecin-Derived Api805 with Increased Bacterial Uptake Rate
In view of the global spread of multiresistant bacteria and the occurrence of panresistant bacteria, there is an urgent need for antimicrobials with novel modes of action. A promising class is antimicrobial peptides (AMPs), including them proline-rich AMPs (PrAMPs), which target the 70S ribosome to inhibit protein translation. Here, we present a new designer peptide, Api805, combining the N- and C-terminal sequences of PrAMPs Api137 and drosocin, respectively. Api805 was similarly active against two Escherichia coli B strains but was inactive against E. coli K12 strain BW25113. These different activities could not be explained by the dissociation constants measured for 70S ribosome preparations from E. coli K12 and B strains. Mutations in the SbmA transporter that PrAMPs use to pass the inner membrane or proteolytic degradation of Api805 by lysate proteases could not explain this either. Interestingly, Api805 seems not to bind to the known binding sites of PrAMPs at the 70S ribosome and inhibited in vitro protein translation, independent of release factors, most likely using a “multimodal effect”. Interestingly, Api805 entered the E. coli B strain Rosetta faster and at larger quantities than the E. coli K-12 strain BW25113, which may be related to the different LPS core structure. In conclusion, slight structural changes in PrAMPs significantly altered their binding sites and mechanisms of action, allowing for the design of different antibiotic classes
Antimicrobial Activity and 70S Ribosome Binding of Apidaecin-Derived Api805 with Increased Bacterial Uptake Rate
In view of the global spread of multiresistant bacteria and the occurrence of panresistant
bacteria, there is an urgent need for antimicrobials with novel modes of action. A promising class is
antimicrobial peptides (AMPs), including them proline-rich AMPs (PrAMPs), which target the 70S
ribosome to inhibit protein translation. Here, we present a new designer peptide, Api805, combining
the N- and C-terminal sequences of PrAMPs Api137 and drosocin, respectively. Api805 was similarly
active against two Escherichia coli B strains but was inactive against E. coli K12 strain BW25113. These
different activities could not be explained by the dissociation constants measured for 70S ribosome
preparations from E. coli K12 and B strains. Mutations in the SbmA transporter that PrAMPs use to
pass the inner membrane or proteolytic degradation of Api805 by lysate proteases could not explain
this either. Interestingly, Api805 seems not to bind to the known binding sites of PrAMPs at the
70S ribosome and inhibited in vitro protein translation, independent of release factors, most likely
using a “multimodal effect”. Interestingly, Api805 entered the E. coli B strain Rosetta faster and at
larger quantities than the E. coli K-12 strain BW25113, which may be related to the different LPS core
structure. In conclusion, slight structural changes in PrAMPs significantly altered their binding sites
and mechanisms of action, allowing for the design of different antibiotic classes
Antimicrobial Activity and 70S Ribosome Binding of Apidaecin-Derived Api805 with Increased Bacterial Uptake Rate
In view of the global spread of multiresistant bacteria and the occurrence of panresistant
bacteria, there is an urgent need for antimicrobials with novel modes of action. A promising class is
antimicrobial peptides (AMPs), including them proline-rich AMPs (PrAMPs), which target the 70S
ribosome to inhibit protein translation. Here, we present a new designer peptide, Api805, combining
the N- and C-terminal sequences of PrAMPs Api137 and drosocin, respectively. Api805 was similarly
active against two Escherichia coli B strains but was inactive against E. coli K12 strain BW25113. These
different activities could not be explained by the dissociation constants measured for 70S ribosome
preparations from E. coli K12 and B strains. Mutations in the SbmA transporter that PrAMPs use to
pass the inner membrane or proteolytic degradation of Api805 by lysate proteases could not explain
this either. Interestingly, Api805 seems not to bind to the known binding sites of PrAMPs at the
70S ribosome and inhibited in vitro protein translation, independent of release factors, most likely
using a “multimodal effect”. Interestingly, Api805 entered the E. coli B strain Rosetta faster and at
larger quantities than the E. coli K-12 strain BW25113, which may be related to the different LPS core
structure. In conclusion, slight structural changes in PrAMPs significantly altered their binding sites
and mechanisms of action, allowing for the design of different antibiotic classes
Antimicrobial Activity and 70S Ribosome Binding of Apidaecin-Derived Api805 with Increased Bacterial Uptake Rate
In view of the global spread of multiresistant bacteria and the occurrence of panresistant bacteria, there is an urgent need for antimicrobials with novel modes of action. A promising class is antimicrobial peptides (AMPs), including them proline-rich AMPs (PrAMPs), which target the 70S ribosome to inhibit protein translation. Here, we present a new designer peptide, Api805, combining the N- and C-terminal sequences of PrAMPs Api137 and drosocin, respectively. Api805 was similarly active against two Escherichia coli B strains but was inactive against E. coli K12 strain BW25113. These different activities could not be explained by the dissociation constants measured for 70S ribosome preparations from E. coli K12 and B strains. Mutations in the SbmA transporter that PrAMPs use to pass the inner membrane or proteolytic degradation of Api805 by lysate proteases could not explain this either. Interestingly, Api805 seems not to bind to the known binding sites of PrAMPs at the 70S ribosome and inhibited in vitro protein translation, independent of release factors, most likely using a “multimodal effect”. Interestingly, Api805 entered the E. coli B strain Rosetta faster and at larger quantities than the E. coli K-12 strain BW25113, which may be related to the different LPS core structure. In conclusion, slight structural changes in PrAMPs significantly altered their binding sites and mechanisms of action, allowing for the design of different antibiotic classes
Antimicrobial and Antibiofilm Activity of UP-5, an Ultrashort Antimicrobial Peptide Designed Using Only Arginine and Biphenylalanine
The recent upsurge of multidrug resistant bacteria (MDRB) among global communities has
become one of the most serious challenges facing health professionals and the human population
worldwide. Cationic ultrashort antimicrobial peptides (USAMPs) are a promising group of molecules
that meet the required criteria of novel antimicrobial drug development. UP-5, a novel penta-peptide,
displayed significant antimicrobial activities against various standard and clinical isolates of MDRB.
UP-5 displayed MICs values within the range of (10–15 M) and (55–65 M) against Gram-positive
and Gram-negative bacteria, respectively. Furthermore, UP-5 displayed antibiofilm activity with
minimum biofilm eradication concentration (MBEC) value as equal to twofold higher than MIC value.
At the same inhibitory concentrations, UP-5 exhibited very low or negligible toxicity toward human
erythrocytes and mammalian cells. Combining UP-5 with conventional antibiotics led to a synergistic
or additive mode of action that resulted in the reduction of the MIC values for some of the antibiotics
by 99.7% along a significant drop in MIC values of the peptide. The stability profile of UP-5 was
evaluated in full mouse plasma and serum with results indicating a more stable pattern in plasma.
The present study indicates that USAMPs are promising antimicrobial agents that can avoid the
negative characteristics of conventional antimicrobial peptides. Additionally, USAMPs exhibit good
to moderate activity against MDRB, negligible toxicity, and synergistic outcomes in combination with
conventional antimicrobial agents
Antimicrobial and Antibiofilm Activity of UP-5, an Ultrashort Antimicrobial Peptide Designed Using Only Arginine and Biphenylalanine
The recent upsurge of multidrug resistant bacteria (MDRB) among global communities has
become one of the most serious challenges facing health professionals and the human population
worldwide. Cationic ultrashort antimicrobial peptides (USAMPs) are a promising group of molecules
that meet the required criteria of novel antimicrobial drug development. UP-5, a novel penta-peptide,
displayed significant antimicrobial activities against various standard and clinical isolates of MDRB.
UP-5 displayed MICs values within the range of (10–15 M) and (55–65 M) against Gram-positive
and Gram-negative bacteria, respectively. Furthermore, UP-5 displayed antibiofilm activity with
minimum biofilm eradication concentration (MBEC) value as equal to twofold higher than MIC value.
At the same inhibitory concentrations, UP-5 exhibited very low or negligible toxicity toward human
erythrocytes and mammalian cells. Combining UP-5 with conventional antibiotics led to a synergistic
or additive mode of action that resulted in the reduction of the MIC values for some of the antibiotics
by 99.7% along a significant drop in MIC values of the peptide. The stability profile of UP-5 was
evaluated in full mouse plasma and serum with results indicating a more stable pattern in plasma.
The present study indicates that USAMPs are promising antimicrobial agents that can avoid the
negative characteristics of conventional antimicrobial peptides. Additionally, USAMPs exhibit good
to moderate activity against MDRB, negligible toxicity, and synergistic outcomes in combination with
conventional antimicrobial agents