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Article ; Online: A proteomic perspective on the resistance response of Klebsiella pneumoniae to antimicrobial peptide PaDBS1R1.

Fleitas, Osmel / Fontes, Wagner / De Souza, Camila M / Da Costa, Mylena C / Cardoso, Marlon H / Castro, Mariana S / Sousa, Marcelo V / Ricart, Carlos A O / Ramada, Marcelo H S / Duque, Harry M / Porto, William F / Silva, Osmar N / Franco, Octávio L

The Journal of antimicrobial chemotherapy

2023 Volume 79, Issue 1, Page(s) 112–122

Abstract: Background: The synthetic antimicrobial peptide, PaDBS1R1, has been reported as a powerful anti-Klebsiella pneumoniae antimicrobial. However, there is only scarce knowledge about whether K. pneumoniae could develop resistance against PaDBS1R1 and which ... ...

Abstract	Background: The synthetic antimicrobial peptide, PaDBS1R1, has been reported as a powerful anti-Klebsiella pneumoniae antimicrobial. However, there is only scarce knowledge about whether K. pneumoniae could develop resistance against PaDBS1R1 and which resistance mechanisms could be involved. Objectives: Identify via label-free shotgun proteomics the K. pneumoniae resistance mechanisms developed against PaDBS1R1. Methods: An adaptive laboratory evolution experiment was performed to obtain a PaDBS1R1-resistant K. pneumoniae lineage. Antimicrobial susceptibility was determined through microdilution assay. Modifications in protein abundances between the resistant and sensitive lineages were measured via label-free quantitative shotgun proteomics. Enriched Gene Ontology terms and KEGG pathways were identified through over-representation analysis. Data are available via ProteomeXchange with identifier PXD033020. Results: K. pneumoniae ATCC 13883 parental strain challenged with increased subinhibitory PaDBS1R1 concentrations allowed the PaDBS1R1-resistant K. pneumoniae lineage to emerge. Proteome comparisons between PaDBS1R1-resistant K. pneumoniae and PaDBS1R1-sensitive K. pneumoniae under PaDBS1R1-induced stress conditions enabled the identification and quantification of 1702 proteins, out of which 201 were differentially abundant proteins (DAPs). The profiled DAPs comprised 103 up-regulated proteins (adjusted P value < 0.05, fold change ≥ 2) and 98 down-regulated proteins (adjusted P value < 0.05, fold change ≤ 0.5). The enrichment analysis suggests that PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery could be relevant resistance mechanisms against PaDBS1R1. Conclusions: Based on experimental evolution and a label-free quantitative shotgun proteomic approach, we showed that K. pneumoniae developed resistance against PaDBS1R1, whereas PhoPQ-guided LPS modifications and CpxRA-dependent folding machinery appear to be relevant resistance mechanisms against PaDBS1R1.
MeSH term(s)	Humans ; Anti-Bacterial Agents/pharmacology ; Klebsiella pneumoniae/genetics ; Antimicrobial Peptides ; Proteomics ; Lipopolysaccharides ; Anti-Infective Agents/pharmacology ; Klebsiella Infections ; Microbial Sensitivity Tests
Chemical Substances	PaDBS1R1 ; Anti-Bacterial Agents ; Antimicrobial Peptides ; Lipopolysaccharides ; Anti-Infective Agents
Language	English
Publishing date	2023-12-02
Publishing country	England
Document type	Journal Article
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkad354
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Article ; Online: Host-defense peptides and their potential use as biomarkers in human diseases.

Silva, Osmar N / Porto, William F / Ribeiro, Suzana M / Batista, Ingrid / Franco, Octavio Luiz

Drug discovery today

2018 Volume 23, Issue 9, Page(s) 1666–1671

Abstract: Since the early 19th century, host-defense peptides (HDPs) have been known to play a crucial role in innate host defense. Subsequent work has demonstrated their role in adaptive immunity as well as their involvement in cancer and also a number of ... ...

Abstract	Since the early 19th century, host-defense peptides (HDPs) have been known to play a crucial role in innate host defense. Subsequent work has demonstrated their role in adaptive immunity as well as their involvement in cancer and also a number of inflammatory and/or autoimmune diseases. In addition to these multiple functional activities, several studies have shown that HDP accumulation might be correlated with various human diseases and, therefore, could be used as a biomarkers for such. Thus, research has aimed to validate the clinical use of HDPs for diagnosis, prognosis, and further treatment. In this review, we outline the most recent findings related to the use of HDPs as biomarkers, their clinical and epidemiological value, and the techniques used to determine the levels of HDPs.
MeSH term(s)	Adaptive Immunity ; Antimicrobial Cationic Peptides/immunology ; Antimicrobial Cationic Peptides/metabolism ; Bacteria/immunology ; Bacteria/metabolism ; Biomarkers/metabolism ; Early Diagnosis ; Host-Pathogen Interactions ; Humans ; Immune System Diseases/diagnosis ; Immune System Diseases/immunology ; Immune System Diseases/metabolism ; Immune System Diseases/therapy ; Immunity, Innate ; Predictive Value of Tests ; Prognosis
Chemical Substances	Antimicrobial Cationic Peptides ; Biomarkers
Language	English
Publishing date	2018-05-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2018.05.024
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Zs.A 4725: Show issues

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Article: Characterization and genetic variability of coat protein genes of Apple chlorotic leaf spot virus isolates from southern Brazil

Nickel, Osmar / Eduardo S. Gorayeb / Fabio N. Silva / Thor V. M. Fajardo

Tropical plant pathology. 2018 Apr., v. 43, no. 2

2018

Abstract: Apple chlorotic leaf spot virus (ACLSV) infects temperate rosaceous fruit trees worldwide and causes a wide range of diseases that are economically highly damaging. This study was carried out to analyze genetic variability of regional ACLSV isolates and ... ...

Abstract	Apple chlorotic leaf spot virus (ACLSV) infects temperate rosaceous fruit trees worldwide and causes a wide range of diseases that are economically highly damaging. This study was carried out to analyze genetic variability of regional ACLSV isolates and compare it with ACLSV isolates from other parts of the world. Nineteen amplicons of ACLSV, corresponding to the coat protein (CP) gene of isolates from apple, plum, and nectarine, from two states in southern Brazil, have been analyzed for genetic variation and compared phylogenetically among themselves and with other sequences available in GenBank. Sequences identities among complete CP genes of these isolates ranged from 87.5 to 100% and 92.2 to 100% at the nucleotide (nt) and the deduced amino acid (daa) levels, respectively. In the comparison with isolates from Asia, Europe and North America, identities were 68.4 to 100% and 72.5 to 100% at nt and daa levels, respectively. Phylogenetic trees based on nucleotide sequences showed that these isolates grouped into two clusters, cluster 1 containing apple isolates and cluster 2 comprising apple, plum and nectarine isolates. Most Brazilian isolates showed conserved signatures (Ser40, Leu59, Tyr75, Thr130 and Leu184) in their CPs, which place them with type B6 isolates. However, some Brazilian isolates were found to be variants of type B6. These analyzes indicated that Brazilian isolates had lower genetic variability compared to isolates from China, India and Japan and that the CP genes were under negative selection. The greatest diversity of nucleotides was observed in the central portion of the CP gene, represented predominantly by synonymous substitutions. One natural recombinant was detected among ACLSV isolates from Brazil.
Keywords	amino acids ; Apple chlorotic leaf spot virus ; apples ; coat proteins ; genes ; genetic variation ; nectarines ; nucleotide sequences ; nucleotides ; phylogeny ; plums ; Brazil ; China ; Europe ; India ; Japan ; North America
Language	English
Dates of publication	2018-04
Size	p. 109-116.
Publishing place	Springer International Publishing
Document type	Article
ZDB-ID	2519866-X
ISSN	1983-2052 ; 1982-5676
ISSN (online)	1983-2052
ISSN	1982-5676
DOI	10.1007/s40858-017-0197-6
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Article ; Online: Preclinical data on morpholine (3,5-di-tertbutyl-4-hydroxyphenyl) methanone induced anxiolysis.

Cabral, Iara Barbosa / de Lima Moreira, Caroline Vitória / Rodrigues, Ana Carolina Cavalcante / da Silva Moreira, Lorrane Kelle / Pereira, Jhon Kennedy Alves / Gomides, Christian Dias / Lião, Luciano M / Machado, Lucas S / Vaz, Boniek G / da Cunha, Luiz Carlos / de Oliveira Neto, Jerônimo Raimundo / da Silva-Júnior, Edeildo Ferreira / de Aquino, Thiago Mendonça / da Silva Santos-Júnior, Paulo Fernando / Silva, Osmar N / da Rocha, Fábio Fagundes / Costa, Elson Alves / Menegatti, Ricardo / Fajemiroye, James O

Naunyn-Schmiedeberg's archives of pharmacology

2023 Volume 396, Issue 11, Page(s) 2957–2975

Abstract: Trimetozine is used to be indicated for the treatment of mental illnesses, particularly anxiety. The present study provides data on the pharmacological profile of trimetozine derivative morpholine (3,5-di-tert-butyl-4-hydroxyphenyl) methanone (LQFM289) ... ...

Abstract	Trimetozine is used to be indicated for the treatment of mental illnesses, particularly anxiety. The present study provides data on the pharmacological profile of trimetozine derivative morpholine (3,5-di-tert-butyl-4-hydroxyphenyl) methanone (LQFM289) which was designed from molecular hybridization of trimetozine lead compound and 2,6-di-tert-butyl-hydroxytoluene to develop new anxiolytic drugs. Here, we conduct molecular dynamics simulations, docking studies, receptor binding assays, and in silico ADMET profiling of LQFM289 before its behavioral and biochemical assessment in mice within the dose range of 5-20 mg/kg. The docking of LQFM289 showed strong interactions with the benzodiazepine binding sites and matched well with receptor binding data. With the ADMET profile of this trimetozine derivative that predicts a high intestinal absorption and permeability to blood-brain barrier without being inhibited by the permeability glycoprotein, the oral administration of LQFM289 10 mg/kg consistently induced anxiolytic-like behavior of the mice exposed to the open field and light-dark box apparatus without eliciting motor incoordination in the wire, rotarod, and chimney tests. A decrease in the wire and rotarod´s fall latency coupled with an increase in the chimney test´s climbing time and a decrease in the number of crossings in the open field apparatus at the dose of 20 mg/kg of this trimetozine derivative suggest sedative or motor coordination impairment at this highest dose. The attenuation of the anxiolytic-like effects of LQFM289 (10 mg/kg) by flumazenil pretreatment implicates the participation of benzodiazepine binding sites. The lowering of corticosterone and tumor necrosis factor alpha (cytokine) in LQFM289-treated mice at a single oral (acute) dose of 10 mg/kg suggests that the anxiolytic-like effect of this compound also involves the recruitment of non-benzodiazepine binding sites/GABAergic molecular machinery.
MeSH term(s)	Mice ; Animals ; Anti-Anxiety Agents/pharmacology ; Anti-Anxiety Agents/therapeutic use ; Benzodiazepines/pharmacology ; Hypnotics and Sedatives/pharmacology ; Anxiety/drug therapy ; Morpholines/pharmacology ; Behavior, Animal
Chemical Substances	Anti-Anxiety Agents ; Benzodiazepines (12794-10-4) ; Hypnotics and Sedatives ; Morpholines
Language	English
Publishing date	2023-04-25
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	121471-8
ISSN	1432-1912 ; 0028-1298
ISSN (online)	1432-1912
ISSN	0028-1298
DOI	10.1007/s00210-023-02502-9
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Article ; Online: Antimicrobial peptides: Role in human disease and potential as immunotherapies.

de la Fuente-Núñez, César / Silva, Osmar N / Lu, Timothy K / Franco, Octavio Luiz

Pharmacology & therapeutics

2017 Volume 178, Page(s) 132–140

Abstract: Antimicrobial peptides (AMPs) have evolved through billions of years as part of our innate immune system. These agents are produced by various cells throughout the human body and play important roles in our ability to respond to infections. In this ... ...

Abstract	Antimicrobial peptides (AMPs) have evolved through billions of years as part of our innate immune system. These agents are produced by various cells throughout the human body and play important roles in our ability to respond to infections. In this review, we outline evidence linking AMP expression with a range of inflammatory and autoimmune human diseases. Finally, we highlight the promise of endogenous AMP induction for the treatment of disease (i.e., host-directed therapy) and briefly mention the different peptide drugs that are currently undergoing clinical trials.
Language	English
Publishing date	2017-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2017.04.002
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Zs.A 1183: Show issues

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Article ; Online: Recombinant probiotics with antimicrobial peptides: a dual strategy to improve immune response in immunocompromised patients.

Mandal, Santi M / Silva, Osmar N / Franco, Octavio L

Drug discovery today

2014 Volume 19, Issue 8, Page(s) 1045–1050

Abstract: Bacterial infectious diseases are currently a serious health problem, especially in patients compromised by illness or those receiving immune-suppressant drugs. In this context, it is not only essential to improve the understanding of infectious ... ...

Abstract	Bacterial infectious diseases are currently a serious health problem, especially in patients compromised by illness or those receiving immune-suppressant drugs. In this context, it is not only essential to improve the understanding of infectious mechanisms and host response but also to discover novel therapies with extreme urgency. Probiotics and antimicrobial peptides are also favorably viewed as novel strategies in the control of resistant bacteria. The present review will shed some light on the use of probiotic microorganisms expressing antimicrobial peptides as a dual therapy to control bacterial infectious diseases.
MeSH term(s)	Animals ; Anti-Infective Agents/immunology ; Anti-Infective Agents/pharmacology ; Anti-Infective Agents/therapeutic use ; Bacteria/drug effects ; Bacteria/immunology ; Bacterial Infections/drug therapy ; Bacterial Infections/immunology ; Humans ; Immunocompromised Host/drug effects ; Immunocompromised Host/immunology ; Peptides/immunology ; Peptides/pharmacology ; Peptides/therapeutic use ; Probiotics/pharmacology ; Probiotics/therapeutic use ; Recombinant Proteins/immunology ; Recombinant Proteins/pharmacology ; Recombinant Proteins/therapeutic use
Chemical Substances	Anti-Infective Agents ; Peptides ; Recombinant Proteins
Language	English
Publishing date	2014-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2014.05.019
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Article ; Online: Perspectives on the Therapeutic Benefits of Arginine Supplementation in Cancer Treatment.

Beal, Fabiani L R / Beal, Pedro R / Beal, Juliana R / Carvalho-Neves, Natan / Franco, Octávio L / Silva, Osmar N

Endocrine, metabolic & immune disorders drug targets

2019 Volume 19, Issue 7, Page(s) 913–920

Abstract: Background: Arginine is considered a semi-essential amino acid in healthy adults and the elderly. This amino acid seems to improve the immune system, stimulate cell growth and differentiation, and increase endothelial permeability, among other effects. ... ...

Abstract	Background: Arginine is considered a semi-essential amino acid in healthy adults and the elderly. This amino acid seems to improve the immune system, stimulate cell growth and differentiation, and increase endothelial permeability, among other effects. For those reasons, it has been theorized that arginine supplementation may be used as an adjuvant to conventional cancer therapy treatments. Objective: This review aims to evaluate the existing knowledge of the scientific community on arginine supplementation in order to improve the efficacy of current cancer treatment. Results: Despite the continued efforts of science to improve treatment strategies, cancer remains one of the greatest causes of death on the planet in adults and elderly people. Chemo and radiotherapy are still the most effective treatments but at the cost of significant side effects. Conclusion: Thus, new therapeutic perspectives have been studied in recent years, to be used in addition to traditional treatments or not, seeking to treat or even cure the various types of cancer with fewer side effects.
MeSH term(s)	Animals ; Antineoplastic Agents/administration & dosage ; Arginine/administration & dosage ; Dietary Supplements ; Humans ; Neoplasms/diagnosis ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2019-01-17
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2228325-0
ISSN	2212-3873 ; 1871-5303
ISSN (online)	2212-3873
ISSN	1871-5303
DOI	10.2174/1871530319666190116121451
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Zs.A 5824: Show issues

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Article ; Online: The fractal based analysis of human face and DNA variations during aging.

Namazi, Hamidreza / Akrami, Amin / Hussaini, Jamal / Silva, Osmar N / Wong, Albert / Kulish, Vladimir V

Bioscience trends

2017 Volume 10, Issue 6, Page(s) 477–481

Abstract: Human DNA is the main unit that shapes human characteristics and features such as behavior. Thus, it is expected that changes in DNA (DNA mutation) influence human characteristics and features. Face is one of the human features which is unique and also ... ...

Abstract	Human DNA is the main unit that shapes human characteristics and features such as behavior. Thus, it is expected that changes in DNA (DNA mutation) influence human characteristics and features. Face is one of the human features which is unique and also dependent on his gen. In this paper, for the first time we analyze the variations of human DNA and face simultaneously. We do this job by analyzing the fractal dimension of DNA walk and face during human aging. The results of this study show the human DNA and face get more complex by aging. These complexities are mapped on fractal exponents of DNA walk and human face. The method discussed in this paper can be further developed in order to investigate the direct influence of DNA mutation on the face variations during aging, and accordingly making a model between human face fractality and the complexity of DNA walk.
MeSH term(s)	Aging/genetics ; Aging/physiology ; Algorithms ; Face ; Fractals ; Humans ; Models, Theoretical ; Mutation
Language	English
Publishing date	2017-01-16
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2543899-2
ISSN	1881-7823 ; 1881-7815
ISSN (online)	1881-7823
ISSN	1881-7815
DOI	10.5582/bst.2016.01182
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Article: High-throughput sequencing applied for the identification of viruses infecting grapevines in Brazil and genetic variability analysis

Fajardo, Thor V. M / FÃ¡bio N. Silva / Marcelo Eiras / Osmar Nickel

Tropical plant pathology. 2017 Aug., v. 42, no. 4

2017

Abstract: The application of high-throughput sequencing technologies (HTS) enables the recovery of many nucleotide sequence fragments from diseased plants and may help in pathogen identification. This study was designed to identify viruses infecting 15 grapevine ( ... ...

Abstract	The application of high-throughput sequencing technologies (HTS) enables the recovery of many nucleotide sequence fragments from diseased plants and may help in pathogen identification. This study was designed to identify viruses infecting 15 grapevine (Vitis spp.) samples collected from experimental fields and vine collections and assess the genetic variability of the identified viruses. The virus-enriched dsRNAs were extracted from bark scrapings and sequenced using an Illumina platform. The paired-end reads were analyzed, assembled contigs were generated and identified as related to viruses. Contigs of 14 viruses have been identified, some of them covering large extensions of viral genomes or resulting in assembly of near-complete or complete genomes. Grapevine virus infections are usually mixed and the HTS assays were suitable to identify ten viruses already reported that traditionally infect grapevines in Brazil, one that has been recently identified (Grapevine Syrah virus 1) and others (Grapevine Cabernet Sauvignon reovirus, Grapevine Red Globe virus and Grapevine vein clearing virus) not previously reported in this country. Nucleotide identities among Brazilian isolates identified by HTS and homologous grapevine virus sequences in GenBank were high, ranging from 77% to 99%. Genetic variability analysis of viral sequences obtained by HTS and sequences available in GenBank indicated that the coding regions in the different viral species are under purifying selection, and that recombination events occurred in the majority of the viral species analyzed. The coat protein genes, generally, had lower genetic variability than the replicase and movement protein genes.
Keywords	Reoviridae ; Vitis ; bark ; coat proteins ; double-stranded RNA ; field experimentation ; genes ; genetic variation ; high-throughput nucleotide sequencing ; nucleotide sequences ; pathogen identification ; plant diseases and disorders ; plant viruses ; vines ; viruses ; Brazil
Language	English
Dates of publication	2017-08
Size	p. 250-260.
Publishing place	Springer International Publishing
Document type	Article
ZDB-ID	2519866-X
ISSN	1983-2052 ; 1982-5676
ISSN (online)	1983-2052
ISSN	1982-5676
DOI	10.1007/s40858-017-0142-8
Database	NAL-Catalogue (AGRICOLA)

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Article: Peptides with Dual Antimicrobial and Anticancer Activities.

Felício, Mário R / Silva, Osmar N / Gonçalves, Sônia / Santos, Nuno C / Franco, Octávio L

Frontiers in chemistry

2017 Volume 5, Page(s) 5

Abstract: In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of ... ...

Abstract	In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting toward intracellular targets, which increases their success compartively to one-target specific drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials.
Language	English
Publishing date	2017-02-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711776-5
ISSN	2296-2646
ISSN	2296-2646
DOI	10.3389/fchem.2017.00005
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