In vitro antibacterial and antimalarial activity of dehydrophenylalanine-containing undecapeptides alone and in combination with drugs

Sharma, Swati; Sharma, Jyotsna; Kanwar, Shamsher S.; Chauhan, Virander S.

doi:10.1016/j.ijantimicag.2011.10.008

Cited by 10 publications

(7 citation statements)

References 30 publications

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“…Polycationic a-helical peptides have been reported to exhibit synergistic effects by enhancing the uptake of some antibiotics. [9][10][11][12][13][14][15] Small cationic cyclic peptides from the polymycin family have also been shown to exhibit synergy with small hydrophobic antibiotics. [16] Therefore, these cationic cyclooctapeptides, in their fast acting capacity to compromise the integrity of bacterial membranes, could present themselves as valuable synergists by enhancing the uptake of some antibiotics.…”

Section: Time Course Assaymentioning

confidence: 99%

“…[9][10][11][12][13] For example, recently Zhang et al reported in vitro synergistic activities of brevinin-2CE in combination with five kinds of antibiotics against clinical isolates of extended-spectrum b-lactamase producing E. coli and methicillin-resistant S. aureus. [14] Anti-methicillin-resistant S. aureus activity of mouse b-defensin 3 in combination with ampicillin has also shown synergism.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Synergy Between Some Cationic Amphipathic Cyclooctapeptides and Antibiotics

et al. 2015

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The antimicrobial activities of some cationic amphipathic cyclooctapeptides in combination with select antibiotics are investigated. Accordingly, cyclooctapeptides (CPs 1-11) derived from the sequence cyclo[Leu-D-Leu-Leu-D-Leu-Lys-DLys-Lys-D-Lys] were tested against Escherichia coli and Staphylococcus aureus. Synergistic effects were evaluated in combination with tetracycline, chloramphenicol, oflaxacin, rifampicin, colistin, clindamycin, and vancomycin by the checkerboard titration assay. The results show that these cyclooctapeptides are fast acting bactericidals and are comparable to the related a-helical peptides in their activities. Significantly, some of these cyclooctapeptides exert selective synergistic effects in combination with the bacteriostatic tetracycline against S. aureus; a greater than 4-fold decrease in the minimum inhibition concentration was observed. Their synergism with the other evaluated antibiotics was generally partial or additive. Cationic amphipathic cyclooctapeptides in combination with some antibiotics could offer a possible solution to the increasing antimicrobial resistance predicament.

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Section: Time Course Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Vitro Synergy Between Some Cationic Amphipathic Cyclooctapeptides and Antibiotics

et al. 2015

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“…Based on the mechanism, glycine produce synergistic effect when combined with CAP, thereby increase its antibacterial effect. CAP / phenylalanine combination antibacterial effect was supported by the finding of (Cockburn et al, 1965;Sharma et al, 2012). The finding of Sharma et al ( 2012) states that phenylalanine (a peptide drug) produce synergistic effect when combined with nonpeptide drug and can be used to battle increasingly drug-resistant microbes.…”

Section: Discussionmentioning

confidence: 92%

“…These amino acids (phenylalanine and glycine) were effective because they were found to have protective and antibacterial effect. Their protective effects were confirmed by the studies of (Asakhiors et al, 2000;Yin et al, 2002;Zhou et al, 2005;Senthikumar et al, 2004;Para-vizuet et al, 2009;Yolande et al, 2011;Ponjit et al, 2011;Manion et al, 2011), while their antibacterial effect were supported by the studies of Minami et al, 2004;Sharma et al, 2012). Due to the limitations of most of the CAP toxicity reduction studies above and to sustain the therapeutic value of CAP in specific indications especially in developing countries, we decided to carry out study directly on bone marrow with the aim to study the effects of phenylalanine (an hydrophobic aromatic ring amino acid) and glycine (an hydrophilic straight chain amino acids) on haematological and histopathological profile of CAP-induced bone marrow toxicity in albino rats infected with Klebsiella pneumoniae.…”

Section: Introductionmentioning

confidence: 83%

Protective effect of phenylalanine and glycine on chloramphenicol-induced bone marrow toxicity in albino rats infected with <i>Klebsiella Pneumoniae</i>

Enendu¹,

Unekwe²,

Esimone³

et al. 2016

Int. J. Bio. Chem. Sci

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The effect of phenylalanine and glycine on chloramphenicol (CAP) induced bone marrow toxicity in albino rats infected with Klebsiella pneumoniae was investigated. The aim was investigate whether the treatment of the infected rats with either of these amino acids or their combination could reverse the major bone marrow toxicity of CAP. The study lasted for a period of 21 days in which haematological and histopathological changes were monitored in the infected rats. After 7 days, the rats became anaemic after treatment with CAP, but amino acids combined groups suppressed the anaemia and infection to some extent. At the end of 21 days, amino acids combination showed significant (p<0.05) suppression of anaemia except in CAP/Phenylalanine/glycine (group 4). Bone marrow examination showed the mechanism involved in the suppression of anaemia (amino acids administration triggered RBC compensatory mechanism seen as erythroid hyperplasia and myeloid hypoplasia). Histopathology changes ranges from hypocellularity in CAP group and fairly normocellularity in CAP/phenylalanine, CAP/glycine and necrotic/degenerative changes in group 4. Single amino acids combination with CAP have obvious protective effect and suppressed the bone marrow toxicity of CAP compared to the combination of the two amino acids with CAP , but all the combinations were effective in enhancing the efficacy of CAP.

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“…Unlike these reports, in the case of cationic CPPs, we noticed that the removal of the supernatant (containing excess peptides) before the addition of a lysis buffer containing SG dye significantly reduced the number of false readouts of antiplasmodial activity of cationic CPP. In one report, the in vitro antiplasmodial activities of cationic undecapeptides were tested using the SG-based fluorescence assay; before adding the lysis buffer containing the SG dye, the supernatant was first removed after treatment to check for peptide-induced hemolysis of the treated cells (26). Although the antimalarial activity of the test peptide was not validated by other methods in that report, it is possible that, in line with our observation, the results were not affected due to the removal of excess peptides in solution.…”

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confidence: 99%

Assessment of SYBR Green I Dye-Based Fluorescence Assay for Screening Antimalarial Activity of Cationic Peptides and DNA Intercalating Agents

Bhatia

Gautam

et al. 2015

Antimicrob Agents Chemother

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bThe SYBR green I (SG) dye-based fluorescence assay for screening antimalarial compounds is based on direct quantitation of parasite DNA. We show that DNA-interacting cationic cell-penetrating peptides (CPPs) and intercalating agents compete with SG dye to bind to DNA. Therefore, readouts of this assay, unlike those of the [ 3 H]hypoxanthine incorporation assay, for the antimalarial activity of the above DNA binding agents may be erroneous. In the case of CPPs, false readouts can be improved by the removal of excess peptides. Malaria continues to be a major public health problem in the 21st century. More than 200 million cases of malaria were reported in 2012, and the emergence of new drug-resistant strains of Plasmodium makes the situation more critical and alarming (1, 2). Chemoresistance, drug monotherapies, the easy availability of substandard drugs, and genetic polymorphism are some of the major causes of parasite drug resistance (3, 4). Thus, it is imperative to identify new antimalarial agents. For antimalarial drug screening, the [ 3 H]hypoxanthine incorporation assay has been a gold standard (5), while parasite lactate dehydrogenase (pLDH)-(6) and histidine-rich protein II-based (7) assays are other widely used methods. However, these assays are expensive and involve multistep procedures and thus are difficult to utilize for highthroughput screening (8, 9). The SYBR green I (SG) dye-based fluorescence assay is a recently developed high-throughput screening method which has been reported to be as sensitive as the [ 3 H]hypoxanthine incorporation assay (8, 10). It has been extensively validated and compared with other known methods and is commonly used for high-throughput antimalarial drug screening (9,(11)(12)(13).Peptides and DNA intercalating agents have been widely tested for their antimalarial activity (14-17). Some cell-penetrating peptides (CPPs), e.g., TP10 (18), and a number of DNA intercalators have been shown to have antimalarial activity (16,17). Interestingly, it has been demonstrated that CPPs, like Tat, penetratin, and TP10, are efficient agents for the delivery of bioactive molecules across the plasma membrane barrier (19). It has also been shown that CPPs move to the nucleus and bind to the target DNA, forming peptide-DNA complexes (20, 21). Since SG dye, CPPs, and intercalating agents bind to DNA, the aim of the present study was to evaluate the suitability of an SG dye-based fluorescence assay for determining the antiplasmodial activity of DNA binding agents. CPPs, Tat, penetratin, TP10, P3, P8 (19,22), and control peptides (Table 1) were chemically synthesized (USV, Mumbai, India) with more than 95% purity. TP10 is a broad-spectrum antiparasitic CPP (18), while Tat has been shown to be nontoxic (at 50 M) to Plasmodium parasites (23). Synchronized Plasmodium falciparum 3D7 cultures at 2% parasitemia and 2% hematocrit were lysed (10) and treated with various concentrations (6.25 M to 100 M) of Tat, penetratin, TP10, and control peptides (control cyclic peptide [CP1] and control linear pe...

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In vitro antibacterial and antimalarial activity of dehydrophenylalanine-containing undecapeptides alone and in combination with drugs

Cited by 10 publications

References 30 publications

In Vitro Synergy Between Some Cationic Amphipathic Cyclooctapeptides and Antibiotics

In Vitro Synergy Between Some Cationic Amphipathic Cyclooctapeptides and Antibiotics

Protective effect of phenylalanine and glycine on chloramphenicol-induced bone marrow toxicity in albino rats infected with <i>Klebsiella Pneumoniae</i>

Assessment of SYBR Green I Dye-Based Fluorescence Assay for Screening Antimalarial Activity of Cationic Peptides and DNA Intercalating Agents

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