Trematocine, a Novel Antimicrobial Peptide from the Antarctic Fish Trematomus bernacchii: Identification and Biological Activity

Antimicrobial peptides (AMPs) are short peptides active against a wide range of pathogens and, therefore, they are considered a useful alternative to conventional antibiotics. We have identified a new AMP in a transcriptome derived from the Antarctic fish Trematomus bernacchii. This peptide, named Trematocine, has been investigated for its expression both at the basal level and after in vivo immunization with an endemic Antarctic bacterium (Psychrobacter sp. TAD1). Results agree with the expected behavior of a fish innate immune component, therefore we decided to synthesize the putative mature sequence of Trematocine to determine the structure, the interaction with biological membranes, and the biological activity. We showed that Trematocine folds into a α-helical structure in the presence of both zwitterionic and anionic charged vesicles. We demonstrated that Trematocine has a highly specific interaction with anionic charged vesicles and that it can kill Gram-negative bacteria, possibly via a carpet like mechanism. Moreover, Trematocine showed minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against selected Gram-positive and Gram-negative bacteria similar to other AMPs isolated from Antarctic fishes. The peptide is a possible candidate for a new drug as it does not show any haemolytic or cytotoxic activity against mammalian cells at the concentration needed to kill the tested bacteria.

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Biological activity of manganese(i) tricarbonyl complexes on multidrug-resistant Gram-negative bacteria: From functional studies to in vivo activity in Galleria mellonella

Metallomics ◽

10.1039/c9mt00224c ◽

2019 ◽

Vol 11 (12) ◽

pp. 2033-2042 ◽

Cited By ~ 9

Author(s):

Paul Güntzel ◽

Christoph Nagel ◽

Jeanette Weigelt ◽

Jono W. Betts ◽

Calum A. Pattrick ◽

...

Keyword(s):

Antibacterial Activity ◽

Biological Activity ◽

Galleria Mellonella ◽

Atp Release ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Bacterial Clearance ◽

Gram Negative ◽

Functional Studies

Antibacterial activity of four Mn(CO)3 complexes on multidrug-resistant clinical isolates of A. baumannii and P. aeruginosa correlated with lipophilicity and increase in ATP release. Absence of host toxicity in G. mellonella was combined with effective bacterial clearance.

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Saccharomyces cerevisiae-Based Molecular Tool Kit for Manipulation of Genes from Gram-Negative Bacteria

Applied and Environmental Microbiology ◽

10.1128/aem.00682-06 ◽

2006 ◽

Vol 72 (7) ◽

pp. 5027-5036 ◽

Cited By ~ 274

Author(s):

Robert M. Q. Shanks ◽

Nicky C. Caiazza ◽

Shannon M. Hinsa ◽

Christine M. Toutain ◽

George A. O'Toole

Keyword(s):

Saccharomyces Cerevisiae ◽

High Efficiency ◽

Opportunistic Pathogen ◽

Single Step ◽

Expression Vectors ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Recombination Proteins ◽

Wide Range

ABSTRACT A tool kit of vectors was designed to manipulate and express genes from a wide range of gram-negative species by using in vivo recombination. Saccharomyces cerevisiae can use its native recombination proteins to combine several amplicons in a single transformation step with high efficiency. We show that this technology is particularly useful for vector design. Shuttle, suicide, and expression vectors useful in a diverse group of bacteria are described and utilized. This report describes the use of these vectors to mutate clpX and clpP of the opportunistic pathogen Pseudomonas aeruginosa and to explore their roles in biofilm formation and surface motility. Complementation of the rhamnolipid biosynthetic gene rhlB is also described. Expression vectors are used for controlled expression of genes in two pseudomonad species. To demonstrate the facility of building complicated constructs with this technique, the recombination of four PCR-generated amplicons in a single step at >80% efficiency into one of these vectors is shown. These tools can be used for genetic studies of pseudomonads and many other gram-negative bacteria.

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The outer membrane proteins OmpA, FhuA, OmpF, EstA, BtuB and OmpX have unique lipopolysaccharide fingerprints

10.1101/448274 ◽

2018 ◽

Author(s):

Jonathan Shearer ◽

Damien Jefferies ◽

Syma Khalid

Keyword(s):

Outer Membrane ◽

Outer Membrane Proteins ◽

Coarse Grain ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Unique Pattern ◽

E Coli ◽

Outer Leaflet ◽

Wide Range

AbstractThe outer membrane of Gram-negative bacteria has a highly complex asymmetrical architecture, containing a mixture of phospholipids in the inner leaflet and in the outer leaflet they contain almost exclusively lipopolysaccharide (LPS) molecules. In E. coli, the outer membrane contains a wide range proteins with a beta barrel architecture, that vary in size from the smallest having eight strands to larger barrels composed of twenty-two strands. Here we report coarse-grain molecular dynamics simulations of six proteins from the E. coli outer membrane OmpA, OmpX, BtuB, FhuA, OmpF and EstA in a range of membrane environments, which are representative of the in vivo for different strains of E. coli. We show that each protein has a unique pattern of interaction with the surrounding membrane, which is influenced by the composition of the protein, the level of LPS in the outer leaflet and the differing mobilities of the lipids in the two leaflets of the membrane. Overall we present analyses from over 200 microseconds of simulation for each protein.Author summaryWe present data from over 200 microseconds of coarse-grain simulations that show the complexities of protein-lipid interactions within the outer membranes of Gram-negative bacteria. We show that the slow movement of lipolysaccharide molecules necessitate simulations of over 30 microsecond duration to achieve converged properties such as protein tilt angle. Each of the six proteins studied here shows a unique pattern of interactions with the outer membrane and thus constitute a ‘fingerprint’ or ‘signature’.

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The antimicrobial potential of cannabidiol

Communications Biology ◽

10.1038/s42003-020-01530-y ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Mark A. T. Blaskovich ◽

Angela M. Kavanagh ◽

Alysha G. Elliott ◽

Bing Zhang ◽

Soumya Ramu ◽

...

Keyword(s):

Bacterial Infections ◽

Modern Medicine ◽

Gram Negative Bacteria ◽

Gram Negative ◽

New Class ◽

Clostridioides Difficile ◽

Excellent Activity ◽

Induce Resistance ◽

First Time

AbstractAntimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.

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Autophagy Deficiency by Atg4B Loss Leads to Metabolomic Alterations in Mice

Metabolites ◽

10.3390/metabo11080481 ◽

2021 ◽

Vol 11 (8) ◽

pp. 481

Author(s):

Gemma G. Martínez-García ◽

Raúl F. Pérez ◽

Álvaro F. Fernández ◽

Sylvere Durand ◽

Guido Kroemer ◽

...

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Mammalian Cells ◽

Tissue Homeostasis ◽

In Vivo Studies ◽

Protective Mechanism ◽

Cardiac Damage ◽

Wide Range ◽

First Time

Autophagy is an essential protective mechanism that allows mammalian cells to cope with a variety of stressors and contributes to maintaining cellular and tissue homeostasis. Due to these crucial roles and also to the fact that autophagy malfunction has been described in a wide range of pathologies, an increasing number of in vivo studies involving animal models targeting autophagy genes have been developed. In mammals, total autophagy inactivation is lethal, and constitutive knockout models lacking effectors of this route are not viable, which has hindered so far the analysis of the consequences of a systemic autophagy decline. Here, we take advantage of atg4b−/− mice, an autophagy-deficient model with only partial disruption of the process, to assess the effects of systemic reduction of autophagy on the metabolome. We describe for the first time the metabolic footprint of systemic autophagy decline, showing that impaired autophagy results in highly tissue-dependent alterations that are more accentuated in the skeletal muscle and plasma. These changes, which include changes in the levels of amino-acids, lipids, or nucleosides, sometimes resemble those that are frequently described in conditions like aging, obesity, or cardiac damage. We also discuss different hypotheses on how impaired autophagy may affect the metabolism of several tissues in mammals.

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Animal Models in the Evaluation of the Effectiveness of Phage Therapy for Infections Caused by Gram-Negative Bacteria from the ESKAPE Group and the Reliability of Its Use in Humans

Microorganisms ◽

10.3390/microorganisms9020206 ◽

2021 ◽

Vol 9 (2) ◽

pp. 206

Author(s):

Martyna Cieślik ◽

Natalia Bagińska ◽

Andrzej Górski ◽

Ewa Jończyk-Matysiak

Keyword(s):

Animal Models ◽

Phage Therapy ◽

Animal Experiments ◽

Species Group ◽

Effectiveness Evaluation ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Enterobacter Species ◽

The Individual

The authors emphasize how extremely important it is to highlight the role played by animal models in an attempt to determine possible phage interactions with the organism into which it was introduced as well as to determine the safety and effectiveness of phage therapy in vivo taking into account the individual conditions of a given organism and its physiology. Animal models in which phages are used make it possible, among other things, to evaluate the effective therapeutic dose and to choose the possible route of phage administration depending on the type of infection developed. These results cannot be applied in detail to the human body, but the knowledge gained from animal experiments is invaluable and very helpful. We would like to highlight how useful animal models may be for the possible effectiveness evaluation of phage therapy in the case of infections caused by gram-negative bacteria from the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species) group of pathogens. In this review, we focus specifically on the data from the last few years.

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In Vitro and In Vivo Antibacterial Activities of DW-224a, a New Fluoronaphthyridone

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01407-05 ◽

2006 ◽

Vol 50 (6) ◽

pp. 2261-2264 ◽

Cited By ~ 36

Author(s):

Hee-Soo Park ◽

Hyun-Joo Kim ◽

Min-Jung Seol ◽

Dong-Rack Choi ◽

Eung-Chil Choi ◽

...

Keyword(s):

Antibacterial Activities ◽

The Other ◽

Vitro Activity ◽

Gram Negative Bacteria ◽

In Vitro Activity ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

ABSTRACT DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.

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RanBP2 and SENP3 Function in a Mitotic SUMO2/3 Conjugation-Deconjugation Cycle on Borealin

Molecular Biology of the Cell ◽

10.1091/mbc.e08-05-0511 ◽

2009 ◽

Vol 20 (1) ◽

pp. 410-418 ◽

Cited By ~ 81

Author(s):

Ulf R. Klein ◽

Markus Haindl ◽

Erich A. Nigg ◽

Stefan Muller

Keyword(s):

Mammalian Cells ◽

Spindle Assembly Checkpoint ◽

Critical Role ◽

Specific Interaction ◽

Regulatory Function ◽

Mitotic Progression ◽

Chromosome Congression ◽

Chromosomal Passenger

The ubiquitin-like SUMO system controls cellular key functions, and several lines of evidence point to a critical role of SUMO for mitotic progression. However, in mammalian cells mitotic substrates of sumoylation and the regulatory components involved are not well defined. Here, we identify Borealin, a component of the chromosomal passenger complex (CPC), as a mitotic target of SUMO. The CPC, which additionally comprises INCENP, Survivin, and Aurora B, regulates key mitotic events, including chromosome congression, the spindle assembly checkpoint, and cytokinesis. We show that Borealin is preferentially modified by SUMO2/3 and demonstrate that the modification is dynamically regulated during mitotic progression, peaking in early mitosis. Intriguingly, the SUMO ligase RanBP2 interacts with the CPC, stimulates SUMO modification of Borealin in vitro, and is required for its modification in vivo. Moreover, the SUMO isopeptidase SENP3 is a specific interaction partner of Borealin and catalyzes the removal of SUMO2/3 from Borealin. These data thus delineate a mitotic SUMO2/3 conjugation–deconjugation cycle of Borealin and further assign a regulatory function of RanBP2 and SENP3 in the mitotic SUMO pathway.

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Cefotaxime and amikacin: results of in vitro and in vivo studies against Gram-negative bacteria and Staphylococcus aureus

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/6.suppl_a.55 ◽

1980 ◽

Vol 6 (suppl A) ◽

pp. 55-61 ◽

Cited By ~ 1

Author(s):

J. Klastersky ◽

H. Gaya ◽

S. H. Zinner ◽

C. Bernard ◽

J-C. Ryff ◽

...

Keyword(s):

Staphylococcus Aureus ◽

In Vivo Studies ◽

Gram Negative Bacteria ◽

Gram Negative ◽

And Staphylococcus Aureus

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Val-Geninthiocin: Structure Elucidation and MSn Fragmentation of Thiopeptide Antibiotics Produced by Streptomyces sp. RSF18

Zeitschrift für Naturforschung B ◽

10.1515/znb-2008-1014 ◽

2008 ◽

Vol 63 (10) ◽

pp. 1223-1230 ◽

Cited By ~ 8

Author(s):

Imran Sajid ◽

Khaled A. Shaaban ◽

Holm Frauendorf ◽

Shahida Hasnain ◽

Hartmut Laatscha

Keyword(s):

Amino Acids ◽

Biological Activity ◽

Antifungal Activity ◽

Structure Elucidation ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Unusual Amino Acids ◽

Streptomyces Sp ◽

Gram Positive Bacteria ◽

Thiopeptide Antibiotics

AbstractVal-Geninthiocin (2), a new member of thiopeptide antibiotics, was isolated from the mycelium of Streptomyces sp. RSF18, along with the closely related geninthiocin (1) and the macrolide, chalcomycin. By intensive NMR and MS studies, Val-geninthiocin (2) was identified as desoxygeninthiocin, a thiopeptide, containing several oxazole and thiazole units and a number of unusual amino acids. Compound 2 shows potent activity against Gram-positive bacteria and minor antifungal activity, while it is not effective against Gram-negative bacteria or microalgae. Here we describe the fermentation, isolation and structure elucidation as well as the biological activity of 2.

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