Novel phospholipase A2 inhibitors from python serum are potent peptide antibiotics

Samy, Ramar Perumal; Thwin, Maung Maung; Stiles, Brad; Satyanarayanajois, Seetharama D.; Chinnathambi, Arunachalam; Zayed, Mohamed E.; Alharbi, Sulaiman Ali; Siveen, Kodappully Sivaraman; Sikka, Sakshi; Kumar, Alan Prem; Sethi, Gautam; Lim, Lina H.K.

doi:10.1016/j.biochi.2015.01.003

Cited by 15 publications

(7 citation statements)

References 85 publications

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“…There are reports in the literature of select antimicrobial peptides with increased activity against Burkholderia sp. [29,30] and the efficacy of these compounds in conjunction with an aminocoumarin would also be worth exploring. …”

Section: Discussionmentioning

confidence: 99%

Identification of synergists that potentiate the action of polymyxin B against Burkholderia cenocepacia

Loutet

El-Halfawy

Jassem

et al. 2015

International Journal of Antimicrobial Agents

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Burkholderia cenocepacia and other members of the Burkholderia cepacia complex (Bcc) are highly multidrug-resistant bacteria that cause severe pulmonary infections in patients with cystic fibrosis. A screen of 2686 compounds derived from marine organisms identified molecules that could synergize with polymyxin B to inhibit growth of B. cenocepacia. At 1 µg/ml, five compounds synergized with polymyxin B and inhibited the growth of B. cenocepacia by more than 70% compared to growth in polymyxin B alone. Follow-up testing revealed that one compound from the screen, the aminocoumarin antibiotic novobiocin, synergized with polymyxin B and colistin against tobramycin-resistant clinical isolates of B. cenocepacia and Burkholderia multivorans. In parallel, we show that novobiocin sensitivity is common among Bcc species and these bacteria are even more susceptible to an alternative aminocoumarin, clorobiocin, which also had an additive effect with polymyxin B against B. cenocepacia. These studies support using aminocoumarin antibiotics to treat Bcc infections and show that synergizers can be found to increase the efficacy of antimicrobial peptides and polymyxins against Bcc bacteria.

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Section: Discussionmentioning

confidence: 99%

Identification of synergists that potentiate the action of polymyxin B against Burkholderia cenocepacia

Loutet

El-Halfawy

Jassem

et al. 2015

International Journal of Antimicrobial Agents

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“…AMPs have made a big impact in antimicrobial research, to diminish the inefficacy of antimicrobial therapy in immunocompromised hosts and also ongoing emergence of resistance to conventional antibiotics worldwide (Giuliani, Pirri & Nicoletto, 2007). Among the AMPs which were reported to demonstrate potential to inhibit B. pseudomallei include LL-37 (Kanthawong et al, 2012), PG1 (Sim et al, 2011), bovine lactoferrin (Puknun et al, 2013), phospholipase A2 (Samy et al, 2015), and SMAP-29 (Blower, Barksdale & van Hoek, 2015). However, there are more potential AMPs that are yet to be tested against B. pseudomallei .…”

Section: Discussionmentioning

confidence: 99%

“…Groups of AMP’s i.e., defensins, cathelicidins, and dermicins have previously been reported to show potential against various pathogens (Wiesner & Vilcinskas, 2010). However, to date, only a few cathelicidin AMPs have been reported to be effective against B. pseudomallei, including LL-37 (Kanthawong et al, 2012), protegrin 1 (PG1) (Sim et al, 2011), bovine lactoferrin (Puknun et al, 2013), phospholipase A2 inhibitors (Samy et al, 2015), and sheep cathelicidin (SMAP-29) (Blower, Barksdale & van Hoek, 2015). …”

Section: Introductionmentioning

confidence: 99%

Antimicrobial activity of Tachyplesin 1 againstBurkholderia pseudomallei: an in vitro and in silico approach

Lee

Mariappan

Vellasamy

et al. 2016

PeerJ

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Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to many conventional antibiotics. Therefore, alternative antimicrobial agents such as antimicrobial peptides (AMPs) are extensively studied to combat this issue. Our study aims to identify and understand the mode of action of the potential AMP(s) that are effective against B. pseudomallei in both planktonic and biofilm state as well as to predict the possible binding targets on using in vitro and in silico approaches. In the in vitro study, 11 AMPs were tested against 100 B. pseudomallei isolates for planktonic cell susceptibility, where LL-37, and PG1, demonstrated 100.0% susceptibility and TP1 demonstrated 83% susceptibility. Since the B. pseudomallei activity was reported on LL-37 and PG1, TP1 was selected for further investigation. TP1 inhibited B. pseudomallei cells at 61.69 μM, and membrane blebbing was observed using scanning electron microscopy. Moreover, TP1 inhibited B. pseudomallei cell growth, reaching bactericidal endpoint within 2 h post exposure as compared to ceftazidime (CAZ) (8 h). Furthermore, TP1 was shown to suppress the growth of B. pseudomallei cells in biofilm state at concentrations above 221 μM. However, TP1 was cytotoxic to the mammalian cell lines tested. In the in silico study, molecular docking revealed that TP1 demonstrated a strong interaction to the common peptide or inhibitor binding targets for lipopolysaccharide of Escherichia coli, as well as autolysin, pneumolysin, and pneumococcal surface protein A (PspA) of Streptococcus pneumoniae. Homology modelled B. pseudomallei PspA protein (YDP) also showed a favourable binding with a strong electrostatic contribution and nine hydrogen bonds. In conclusion, TP1 demonstrated a good potential as an anti-B. pseudomallei agent.

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“…Besides potent neutralization effects against Crotalus adamanteus snake venom, PIP18 has shown high bactericidal action against a number of pathogens, in a dose-dependent manner, with a remarkable activity against Staphylococcus aureus. Topical application of PIP18 has also modulated in vivo wound repair in a mouse model of S. aureus infection [49]. …”

Section: Gamma Class Of Sbplis (Sbγplis)mentioning

confidence: 99%

Endogenous phospholipase A2 inhibitors in snakes: a brief overview

Campos-Júnior

Melo

Dias

et al. 2016

J Venom Anim Toxins Incl Trop Dis

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The blood plasma of numerous snake species naturally comprises endogenous phospholipase A2 inhibitors, which primarily neutralize toxic phospholipases A2 that may eventually reach their circulation. This inhibitor type is generally known as snake blood phospholipase A2 inhibitors (sbPLIs). Most, if not all sbPLIs are oligomeric glycosylated proteins, although the carbohydrate moiety may not be essential for PLA2 inhibition in every case. The presently known sbPLIs belong to one of three structural classes – namely sbαPLI, sbβPLI or sbγPLI – depending on the presence of characteristic C-type lectin-like domains, leucine-rich repeats or three-finger motifs, respectively. Currently, the most numerous inhibitors described in the literature are sbαPLIs and sbγPLIs, whereas sbβPLIs are rare. When the target PLA2 is a Lys49 homolog or an Asp49 myotoxin, the sbPLI is denominated a myotoxin inhibitor protein (MIP). In this brief overview, the most relevant data on sbPLIs will be presented. Representative examples of sbαPLIs and sbγPLIs from two Old World – Gloydius brevicaudus and Malayopython reticulatus – and two New World – Bothrops alternatus and Crotalus durissus terrificus – snake species will be emphasized.

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Novel phospholipase A2 inhibitors from python serum are potent peptide antibiotics

Cited by 15 publications

References 85 publications

Identification of synergists that potentiate the action of polymyxin B against Burkholderia cenocepacia

Identification of synergists that potentiate the action of polymyxin B against Burkholderia cenocepacia

Antimicrobial activity of Tachyplesin 1 againstBurkholderia pseudomallei: an in vitro and in silico approach

Endogenous phospholipase A2 inhibitors in snakes: a brief overview

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