Effects of Chlorophyll-Derived Efflux Pump Inhibitor Pheophorbide<i>a</i>and Pyropheophorbide<i>a</i>on Growth and Macrolide Antibiotic Resistance of Indicator and Anaerobic Swine Manure Bacteria

Kraatz, Mareike; Whitehead, Terence R.; Cotta, Michael A.; Berhow, Mark; Rasmussen, Mark A.

doi:10.1155/2014/185068

Cited by 9 publications

(12 citation statements)

References 111 publications

(175 reference statements)

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“…This hypothesis is consistent with our observation that the midgut preferentially binds chlorophyllide over chlorophyll. Tetrapyrrole molecules are known to bind a variety of proteins and to inhibit their functions (Miller and Shaklai, 1999;Golovina et al, 2013;Kraatz et al, 2014). For example, pheophorbide a is an inhibitor of the enzyme, cholesterol acyltransferase (Song et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Reexamination of Chlorophyllase Function Implies Its Involvement in Defense against Chewing Herbivores

Makita

Schelbert

et al. 2015

Plant Physiol.

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Chlorophyllase (CLH) is a common plant enzyme that catalyzes the hydrolysis of chlorophyll to form chlorophyllide, a more hydrophilic derivative. For more than a century, the biological role of CLH has been controversial, although this enzyme has been often considered to catalyze chlorophyll catabolism during stress-induced chlorophyll breakdown. In this study, we found that the absence of CLH does not affect chlorophyll breakdown in intact leaf tissue in the absence or the presence of methyljasmonate, which is known to enhance stress-induced chlorophyll breakdown. Fractionation of cellular membranes shows that Arabidopsis (Arabidopsis thaliana) CLH is located in the endoplasmic reticulum and the tonoplast of intact plant cells. These results indicate that CLH is not involved in endogenous chlorophyll catabolism. Instead, we found that CLH promotes chlorophyllide formation upon disruption of leaf cells, or when it is artificially mistargeted to the chloroplast. These results indicate that CLH is responsible for chlorophyllide formation after the collapse of cells, which led us to hypothesize that chlorophyllide formation might be a process of defense against chewing herbivores. We found that Arabidopsis leaves with genetically enhanced CLH activity exhibit toxicity when fed to Spodoptera litura larvae, an insect herbivore. In addition, purified chlorophyllide partially suppresses the growth of the larvae. Taken together, these results support the presence of a unique binary defense system against insect herbivores involving chlorophyll and CLH. Potential mechanisms of chlorophyllide action for defense are discussed.

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Section: Discussionmentioning

confidence: 99%

Reexamination of Chlorophyllase Function Implies Its Involvement in Defense against Chewing Herbivores

Makita

Schelbert

et al. 2015

Plant Physiol.

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“…The bioactive compounds in fraction 3 of Surian leaves responsible for antibacterial activity against acne bacteria were pheophorbide a, pheophytin a and dihomo-γ-linolenic acid (Table 4). Kraatz et al (2014) reported that pheophorbide a could inhibit the growth of S. aureus and E. coli that are resistant to erythromycin and showed MIC of 50 μg/mL. Gomes et al (2015) also found that antibacterial activity of pheophytin, isolated from Sidastrum micranthum, was capable to suppress the growth of S. aureus, S. epidermidis, and E. coli with MIC of 75 μg/mL.…”

Section: Discussionmentioning

confidence: 97%

Identification of active compounds and anti-acne activity from extracts and fractions of surian (Toona sinensis) leaves planted in Sumedang, West Java, Indonesia

et al. 2018

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Febriyani E, Falah S, Andrianto D, Lastini T. 2018. Identification of active compounds and anti-acne activity from extractsand fractions of surian (Toona sinensis) leaves planted in Sumedang, West Java, Indonesia. Biodiversitas 19: 1406-1412. Surian or toon(Toona sinensis Merr) leave is one of the herbs containing many bioactive compounds as potential sources of anti-acne agents. The aimof this work is to identify and evaluate the anti-acne activity of Surian leaves extract and fractions against acne bacteria. Crude extractsof Surian leaves from various solvents (methanol, ethanol, and ethyl acetate) were screened for their antimicrobial activity using discdiffusion. The results showed that ethyl acetate extract demonstrated the highest inhibition against Propionibacterium acne (49.93%),Staphylococcus epidermidis (57.14%), Staphylococcus aureus (18.93%), and Eschericia coli (82.03%). The results of Brine ShrimpLethality Test (BSLT) showed that the methanol extract had the highest cytotoxicity of LC50 at 29.76 μg/mL. The extract was thenfractionated using column chromatography, resulted in 6 fractions. The fraction 3 showed the best antibacterial effect against P. acne(28.27%), S. epidermidis (7.38%) and S. aureus (10.38%). Minimum inhibitory concentration (MIC) and minimal bactericidalconcentration (MBC) test were carried out using liquid dilution, whereas dimethyl sulfoxide (DMSO) and Clindamycin were used as anegative and positive control, respectively. The MIC and MBC test assays of fraction 3 varied for different bacteria P. acne bacteria(5000 and 5000 ppm), S. aureus (1250 and 10000 ppm), E. coli (2500 and 5000 ppm), while for S. epidermidis the fraction 3 was able toinhibit with MIC value of 5000 ppm. Based on microscopic observation using Scanning Electron Microscope (SEM), the fraction 3 atthe dose of 5000 ppm could promote the cellular destruction of P. acne. Further experiment using Liquid Chromatography-TendemMass Spectrometry (LC-MS/MS) showed various compounds associated with the anti-acne activity of the fraction 3, such aspheophorbide a, pheophytin a and dihomo-γ-linolenic acid.

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“…PhA has low solubility and permeability, and, as a Bcrp substrate, is poorly absorbed, which was reflected in PhA being detected in the intestine of PhA-gavaged mice, but was undetectable in the serum of WT mice gavaged with PhA. PhA has been reported to be mainly cleared unabsorbed in feces (Kraatz et al, 2014). Interestingly, we routinely found that ex vivo fluorescence comparison of the intestinal segments of WT mice fed a normal PhA-containing diet, after flushing out the intestinal contents, revealed a lower PhA fluorescence in the duodenum compared with a higher PhA fluorescence in the jejunum and ileum.…”

Section: Discussionmentioning

confidence: 99%

“…An ideal assay for Bcrp activity would use a specific, inexpensive, fluorescent near-infrared (NIR) substrate probe that could be monitored in real time both in vitro (high-throughput) and in vivo. PhA is a breakdown product of chlorophyll and is a specific dietary substrate of Bcrp (Jonker et al, 2002;Robey et al, 2004;Kraatz et al, 2014), with an efflux ratio of 3.15 in cell lines overexpressing Bcrp (Zhang et al, 2009). Two laboratories have developed in vitro assays for BCRP function/inhibition using PhA, also showing that PhA is not a substrate for P-glycoprotein or MRP1 in vitro (Robey et al, 2004(Robey et al, , 2005.…”

Section: Introductionmentioning

confidence: 99%

Pheophorbide A: Fluorescent Bcrp Substrate to Measure Oral Drug-Drug Interactions in Real-Time In Vivo

2018

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We investigated whether pheophorbide A (PhA) could serve as a selective breast cancer resistance protein (BCRP) substrate (victim) to screen in vivo using fluorescent live animal imaging for transporter-mediated interactions with orally administered inhibitors (perpetrators), and whether that could be coupled with serum sampling to measure the systemic concentration of PhA with a fast-throughput in vitro fluorescent assay. PhA is a breakdown product of chlorophyll and is highly fluorescent in the near-infrared (NIR) spectrum. Whole-body NIR fluorescence was greater in the Bcrp KO compared with wild-type (WT) mice fed a regular diet containing chlorophyll and PhA, with fluorescence in WT mice confined to the intestine. PhA intestinal enterocyte fluorescence, after removing lumen contents, was greater in Bcrp knockout (KO) mice versus WT mice due to PhA enterocyte absorption and lack of PhA efflux by Bcrp. This difference was eliminated by maintaining the mice on an alfalfa (chlorophyll/PhA)-free diet. The area under the fluorescence ratio-time curve up to 6 hours (AUC) of orally administrated PhA was 3.5 times greater in the Bcrp KO mice compared with WT mice, and the PhA serum concentration was 50-fold higher in KO mice. Pretreatment with known BCRP inhibitors lapatinib, curcumin, elacridar, pantoprazole, and sorafenib, at clinically relevant doses, significantly increased PhA AUC by 2.4-, 2.3-, 2.2-, 1.5-, and 1.4-fold, respectively, whereas the area under PhA serum concentration-time curve calculated up to 6 hours (AUC) increased by 13.8-, 7.8-, 5.2-, 2.02-, and 1.45-fold, respectively, and corresponded to their hierarchy as in vitro BCRP inhibitors. Our results demonstrate that live animal imaging using PhA can be used to identify BCRP inhibitors and to assess the potential for BCRP-mediated clinical drug-drug interactions.

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Effects of Chlorophyll-Derived Efflux Pump Inhibitor Pheophorbideaand Pyropheophorbideaon Growth and Macrolide Antibiotic Resistance of Indicator and Anaerobic Swine Manure Bacteria

Cited by 9 publications

References 111 publications

Reexamination of Chlorophyllase Function Implies Its Involvement in Defense against Chewing Herbivores

Reexamination of Chlorophyllase Function Implies Its Involvement in Defense against Chewing Herbivores

Identification of active compounds and anti-acne activity from extracts and fractions of surian (Toona sinensis) leaves planted in Sumedang, West Java, Indonesia

Pheophorbide A: Fluorescent Bcrp Substrate to Measure Oral Drug-Drug Interactions in Real-Time In Vivo

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