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Isolation, Phylogenetic Analysis and Anti-infective Activity Screening of Marine Sponge-Associated Actinomycetes  [PDF]
Usama Ramadan Abdelmohsen,Sheila M. Pimentel-Elardo,Amro Hanora,Mona Radwan,Soad H. Abou-El-Ela,Safwat Ahmed,Ute Hentschel
Marine Drugs , 2010, DOI: 10.3390/md8030399
Abstract: Terrestrial actinomycetes are noteworthy producers of a multitude of antibiotics, however the marine representatives are much less studied in this regard. In this study, 90 actinomycetes were isolated from 11 different species of marine sponges that had been collected from offshore Ras Mohamed (Egypt) and from Rovinj (Croatia). Phylogenetic characterization of the isolates based on 16S rRNA gene sequencing supported their assignment to 18 different actinomycete genera representing seven different suborders. Fourteen putatively novel species were identified based on sequence similarity values below 98.2% to other strains in the NCBI database. A putative new genus related to Rubrobacter was isolated on M1 agar that had been amended with sponge extract, thus highlighting the need for innovative cultivation protocols. Testing for anti-infective activities was performed against clinically relevant, Gram-positive ( Enterococcus faecalis, Staphylococcus aureus) and Gram-negative ( Escherichia coli, Pseudomonas aeruginosa) bacteria, fungi ( Candida albicans) and human parasites ( Leishmania major, Trypanosoma brucei). Bioactivities against these pathogens were documented for 10 actinomycete isolates. These results show a high diversity of actinomycetes associated with marine sponges as well as highlight their potential to produce anti-infective agents.
Anti-infective activity of apolipoprotein domain derived peptides in vitro: identification of novel antimicrobial peptides related to apolipoprotein B with anti-HIV activity
Bridie A Kelly, Ian Harrison, áine McKnight, Curtis B Dobson
BMC Immunology , 2010, DOI: 10.1186/1471-2172-11-13
Abstract: Of the nineteen new peptides tested, seven showed some anti-infective activity, with two of these being derived from two apolipoproteins not previously used to derive anti-infective sequences. Apolipoprotein J (151-170) - based on a predicted amphipathic alpha-helical domain from apolipoprotein J - had measurable anti-HSV1 activity, as did apolipoprotein B (3359-3367) dp (apoBdp), the latter being derived from the LDL receptor binding domain B of apolipoprotein B. The more active peptide - apoBdp - showed similarity to the previously reported apoE derived anti-infective peptide, and further modification of the apoBdp sequence to align the charge distribution more closely to that of apoEdp or to introduce aromatic residues resulted in increased breadth and potency of activity. The most active peptide of this type showed similar potent anti-HIV activity, comparable to that we previously reported for the apoE derived peptide apoEdpL-W.These data suggest that further antimicrobial peptides may be obtained using human apolipoprotein sequences, selecting regions with either amphipathic α-helical structure, or those linked to receptor-binding regions. The finding that an amphipathic α-helical region of apolipoprotein J has antiviral activity comparable with that for the previously reported apolipoprotein AI derived peptide 18A, suggests that full-length apolipoprotein J may also have such activity, as has been reported for full-length apolipoprotein AI. Although the strength of the anti-infective activity of the sequences identified was limited, this could be increased substantially by developing related mutant peptides. Indeed the apolipoprotein B-derived peptide mutants uncovered by the present study may have utility as HIV therapeutics or microbicides.A number of studies have reported molecular interactions between viruses and lipoproteins (LPs), apolipoproteins or their receptors, with an underlying basis for these links being the similarities in location, size and fun
Novel Anti-Infective Compounds from Marine Bacteria  [PDF]
Hafizur Rahman,Brian Austin,Wilfrid J. Mitchell,Peter C. Morris,Derek J. Jamieson,David R. Adams,Andrew Mearns Spragg,Michael Schweizer
Marine Drugs , 2010, DOI: 10.3390/md8030498
Abstract: As a result of the continuous evolution of microbial pathogens towards antibiotic-resistance, there have been demands for the development of new and effective antimicrobial compounds. Since the 1960s, the scientific literature has accumulated many publications about novel pharmaceutical compounds produced by a diverse range of marine bacteria. Indeed, marine micro-organisms continue to be a productive and successful focus for natural products research, with many newly isolated compounds possessing potentially valuable pharmacological activities. In this regard, the marine environment will undoubtedly prove to be an increasingly important source of novel antimicrobial metabolites, and selective or targeted approaches are already enabling the recovery of a significant number of antibiotic-producing micro-organisms. The aim of this review is to consider advances made in the discovery of new secondary metabolites derived from marine bacteria, and in particular those effective against the so called “superbugs”, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE), which are largely responsible for the increase in numbers of hospital acquired, i.e., nosocomial, infections.
Anti-Infective Potential of Marine Invertebrates and Seaweeds from the Brazilian Coast  [PDF]
éverson Miguel Bianco,Simone Quintana de Oliveira,Caroline Rigotto,Maiko Luis Tonini,Tatiana da Rosa Guimar?es,Francine Bittencourt,Lidiane Pires Gouvêa,Cassandra Aresi,Maria Tereza Rojo de Almeida,Maria Izabel Goularte Moritz,Cintia Dalcuche Leal Martins,Fernando Scherner,Jo?o Luís Carraro,Paulo Antunes Horta,Flávio Henrique Reginatto,Mario Steindel,Cláudia Maria Oliveira Sim?es,Eloir Paulo Schenkel
Molecules , 2013, DOI: 10.3390/molecules18055761
Abstract: This manuscript describes the evaluation of anti-infective potential in vitro of organic extracts from nine sponges, one ascidian, two octocorals, one bryozoan, and 27 seaweed species collected along the Brazilian coast. Antimicrobial activity was tested against Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 10231) by the disk diffusion method. Antiprotozoal activity was evaluated against Leishmania braziliensis (MHOM/BR/96/LSC96-H3) promastigotes and Trypanosoma cruzi (MHOM/BR/00/Y) epimastigotes by MTT assay. Activity against intracellular amastigotes of T. cruzi and L. brasiliensis in murine macrophages was also evaluated. Antiviral activity was tested against Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the plaque number reduction assay (IC 50). Cytotoxicity on VERO cells was evaluated by the MTT assay (CC 50). The results were expressed as SI = CC 50/IC 50. The most promising antimicrobial results were obtained against S. aureus and C. albicans with Dragmacidon reticulatum. Among the seaweeds, only Osmundaria obtusiloba showed moderate activity against P. aeruginosa. Concerning antiprotozoal activity, Bugula neritina, Carijoa riseii, Dragmaxia anomala and Haliclona ( Halichoclona) sp. showed the most interesting results, mainly against extracellular promastigote forms of L. braziliensis (66, 35.9, 97.2, and 43.6% inhibition, respectively). Moreover, six species of seaweeds Anadyomene saldanhae, Caulerpa cupressoides, Canistrocarpus cervicornis, Dictyota sp., Ochtodes secundiramea, and Padina sp. showed promising results against L. braziliensis (87.9, 51.7, 85.9, 93.3, 99.7, and 80.9% inhibition, respectively), and only Dictyota sp. was effective against T. cruzi (60.4% inhibition). Finally, the antiherpes activity was also evaluated, with Haliclona ( Halichoclona) sp. and Petromica citrina showing the best results (SI = 11.9 and SI > 5, respectively). All the active extracts deserve special attention in further studies to chemically characterize the bioactive compounds, and to perform more refined biological assays.
Host Defense Peptides as Effector Molecules of the Innate Immune Response: A Sledgehammer for Drug Resistance?  [PDF]
Lars Steinstraesser,Ursula M. Kraneburg,Tobias Hirsch,Marco Kesting,Hans-Ulrich Steinau,Frank Jacobsen,Sammy Al-Benna
International Journal of Molecular Sciences , 2009, DOI: 10.3390/ijms10093951
Abstract: Host defense peptides can modulate the innate immune response and boost infection-resolving immunity, while dampening potentially harmful pro-inflammatory (septic) responses. Both antimicrobial and/or immunomodulatory activities are an integral part of the process of innate immunity, which itself has many of the hallmarks of successful anti-infective therapies, namely rapid action and broad-spectrum antimicrobial activities. This gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections. This review details the role and activities of these peptides, and examines their applicability as development candidates for use against bacterial infections.
6. Anti-infective activities of Sookshma Triphala in abdominal sepsis induced by cecal ligation in rats
Jayshree S. Dawane,Vijaya A. Pandit,Kanchan D. Borole,S.D. Kulkarni
International Journal of Pharmaceutical and Biomedical Research (IJPBR) , 2011,
Abstract: In spite of large number of antimicrobial agents available, treatment of infections still poses a problem. In Ayurveda, many agents are used for prevention and treatment of infections. Sookshma Triphala is one of such formulation. Efforts were made to evaluate the anti-infective effect of Sookshma Triphala in abdominal sepsis induced by caecal ligation in rats. The objective of the present study is to investigate the efficacy of Sookshma Triphala in abdominal sepsis in rats. 24 Albino wistar rats were divided into four groups of 6 each. All animals received pretreatment for 14 days except one group which received Sookshma Triphala only postoperatively. Sookshma Triphala was given in the dose 100 and 200 mg/kg to different groups. Rats, fasting overnight, were given Phenobarbitone anesthesia and caecal ligation was performed under strict aseptic precautions. Animals were observed postoperatively for mortality over 5 days. Animals survived upto 5th postoperative day were sacrificed and Inspection of abdominal cavity was done. Sepsis was scored. Sookshma Triphala treatment effectively reduced mortality and produced localization of abdominal sepsis in dose dependent manner. Wound healing was better in Sookshma Triphala treated group than control. Sookshma Triphala improved the survival rate and reduced sepsis score, thus it appears to be a promising formulation against infection.
Host-Defense Peptides with Therapeutic Potential from Skin Secretions of Frogs from the Family Pipidae  [PDF]
J. Michael Conlon,Milena Mechkarska
Pharmaceuticals , 2014, DOI: 10.3390/ph7010058
Abstract: Skin secretions from frogs belonging to the genera Xenopus, Silurana, Hymenochirus, and Pseudhymenochirus in the family Pipidae are a rich source of host-defense peptides with varying degrees of antimicrobial activities and cytotoxicities to mammalian cells. Magainin, peptide glycine-leucine-amide (PGLa), caerulein-precursor fragment (CPF), and xenopsin-precursor fragment (XPF) peptides have been isolated from norepinephrine-stimulated skin secretions from several species of Xenopus and Silurana. Hymenochirins and pseudhymenochirins have been isolated from Hymenochirus boettgeri and Pseudhymenochirus merlini. A major obstacle to the development of these peptides as anti-infective agents is their hemolytic activities against human erythrocytes. Analogs of the magainins, CPF peptides and hymenochirin-1B with increased antimicrobial potencies and low cytotoxicities have been developed that are active (MIC < 5 μM) against multidrug-resistant clinical isolates of Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Klebsiella pneumoniae. Despite this, the therapeutic potential of frog skin peptides as anti-infective agents has not been realized so that alternative clinical applications as anti-cancer, anti-viral, anti-diabetic, or immunomodulatory drugs are being explored.
Epigenetic Tailoring for the Production of Anti-Infective Cytosporones from the Marine Fungus Leucostoma persoonii  [PDF]
Jeremy Beau,Nida Mahid,Whittney N. Burda,Lacey Harrington,Lindsey N. Shaw,Tina Mutka,Dennis E. Kyle,Betty Barisic,Alberto van Olphen,Bill J. Baker
Marine Drugs , 2012, DOI: 10.3390/md10040762
Abstract: Recent genomic studies have demonstrated that fungi can possess gene clusters encoding for the production of previously unobserved secondary metabolites. Activation of these attenuated or silenced genes to obtain either improved titers of known compounds or new ones altogether has been a subject of considerable interest. In our efforts to discover new chemotypes that are effective against infectious diseases, including malaria and methicillin-resistant Staphylococcus aureus (MRSA), we have isolated a strain of marine fungus, Leucostoma persoonii, that produces bioactive cytosporones. Epigenetic modifiers employed to activate secondary metabolite genes resulted in enhanced production of known cytosporones B ( 1, 360%), C ( 2, 580%) and E ( 3, 890%), as well as the production of the previously undescribed cytosporone R ( 4). Cytosporone E was the most bioactive, displaying an IC 90 of 13 μM toward Plasmodium falciparum, with A549 cytotoxicity IC 90 of 437 μM, representing a 90% inhibition therapeutic index (TI 90 = IC 90 A459/IC 90 P. falciparum) of 33. In addition, cytosporone E was active against MRSA with a minimal inhibitory concentration (MIC) of 72 μM and inhibition of MRSA biofilm at roughly half that value (minimum biofilm eradication counts, MBEC90, was found to be 39 μM).
Conventional and Unconventional Antimicrobials from Fish, Marine Invertebrates and Micro-algae  [PDF]
Valerie J. Smith,Andrew P. Desbois,Elisabeth A. Dyrynda
Marine Drugs , 2010, DOI: 10.3390/md8041213
Abstract: All eukaryotic organisms, single-celled or multi-cellular, produce a diverse array of natural anti-infective agents that, in addition to conventional antimicrobial peptides, also include proteins and other molecules often not regarded as part of the innate defences. Examples range from histones, fatty acids, and other structural components of cells to pigments and regulatory proteins. These probably represent very ancient defence factors that have been re-used in new ways during evolution. This review discusses the nature, biological role in host protection and potential biotechnological uses of some of these compounds, focusing on those from fish, marine invertebrates and marine micro-algae.
Anti-Chikungunya Viral Activities of Aplysiatoxin-Related Compounds from the Marine Cyanobacterium Trichodesmium erythraeum  [PDF]
Deepak Kumar Gupta,Parveen Kaur,See Ting Leong,Lik Tong Tan,Michèle R. Prinsep,Justin Jang Hann Chu
Marine Drugs , 2014, DOI: 10.3390/md12010115
Abstract: Tropical filamentous marine cyanobacteria have emerged as a viable source of novel bioactive natural products for drug discovery and development. In the present study, aplysiatoxin ( 1), debromoaplysiatoxin ( 2) and anhydrodebromoaplysiatoxin ( 3), as well as two new analogues, 3-methoxyaplysiatoxin ( 4) and 3-methoxydebromoaplysiatoxin ( 5), are reported for the first time from the marine cyanobacterium Trichodesmium erythraeum. The identification of the bloom-forming cyanobacterial strain was confirmed based on phylogenetic analysis of its 16S rRNA sequences. Structural determination of the new analogues was achieved by extensive NMR spectroscopic analysis and comparison with NMR spectral data of known compounds. In addition, the antiviral activities of these marine toxins were assessed using Chikungunya virus (CHIKV)-infected cells. Post-treatment experiments using the debrominated analogues, namely compounds 2, 3 and 5, displayed dose-dependent inhibition of CHIKV when tested at concentrations ranging from 0.1 μM to 10.0 μM. Furthermore, debromoaplysiatoxin ( 2) and 3-methoxydebromoaplysiatoxin ( 5) exhibited significant anti-CHIKV activities with EC 50 values of 1.3 μM and 2.7 μM, respectively, and selectivity indices of 10.9 and 9.2, respectively.
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