In vitro activity of PR-39, a proline-arginine-rich peptide, against susceptible and multi-drug-resistant Mycobacterium tuberculosis

Linde, Charlotte; Hoffner, Sven; Refai, Essam; Andersson, Mats

doi:10.1093/jac/47.5.575

Cited by 80 publications

(49 citation statements)

References 30 publications

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“…Synthetic and natural forms of the peptide are active for Gram-negative bacteria only and MICs range from 1 Á/4 mM [58,62]. However, PR-39 is active against drug-susceptible as well as multi-drug-resistant clinical isolates of Mycobacterium tuberculosis [63].…”

Section: Linear Peptides Rich In Prolinementioning

confidence: 99%

Antimicrobial peptides in animals and their role in host defences

Brogden

Ackermann

McCray

et al. 2003

International Journal of Antimicrobial Agents

418

287

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Domesticated animals have a large variety of antimicrobial peptides that serve as natural innate barriers limiting microbial infection or, in some instances, act as an integral component in response to inflammation or microbial infection. These peptides differ in size, composition, mechanisms of activity and range of antimicrobial specificities. They are expressed in many tissues, polymorphonuclear leukocytes, macrophages and mucosal epithelial cells. There is a small group of anionic antimicrobial peptides found in ruminants and a much larger group of cationic antimicrobial peptides found in all domesticated animals. The cationic peptides include linear, helical peptides, linear peptides rich in proline and cysteine-stabilized peptides with a b-sheet and are commonly referred to as cathelicidins and defensins. These peptides are generally broad-spectrum for Gram-positive bacteria, Gram-negative bacteria and fungi (e.g. myeloid antimicrobial peptides, a-, bdefensins, and protegrins) or are specific to one of these groups (e.g. porcine cecropin P1, Bac5, Bac7, PR-39 and prophenin). RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. Abstract Domesticated animals have a large variety of antimicrobial peptides that serve as natural innate barriers limiting microbial infection or, in some instances, act as an integral component in response to inflammation or microbial infection. These peptides differ in size, composition, mechanisms of activity and range of antimicrobial specificities. They are expressed in many tissues, polymorphonuclear leukocytes, macrophages and mucosal epithelial cells. There is a small group of anionic antimicrobial peptides found in ruminants and a much larger group of cationic antimicrobial peptides found in all domesticated animals. The cationic peptides include linear, helical peptides, linear peptides rich in proline and cysteine-stabilized peptides with a b-sheet and are commonly referred to as cathelicidins and defensins. These peptides are generally broad-spectrum for Gram-positive bacteria, Gram-negative bacteria and fungi (e.g. myeloid antimicrobial peptides, a-, b-defensins, and protegrins) or are specific to one of these groups (e.g. porcine cecropin P1, Bac5, Bac7, PR-39 and prophenin). Published by Elsevier B.V.

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Section: Linear Peptides Rich In Prolinementioning

confidence: 99%

Antimicrobial peptides in animals and their role in host defences

Brogden

Ackermann

McCray

et al. 2003

International Journal of Antimicrobial Agents

418

287

View full text Add to dashboard Cite

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“…Aliquots (100 l) of twofold serial dilutions of SP (same initial concentrations as given above) were added to each well (200-l total volume). The plates were incubated at 35°C, and readings were taken at 24 and 48 h. For M. smegmatis MIC determinations, cells were grown to a density of 1.0 McFarland standard (3 ϫ 10 8 CFU per ml) (23). Inocula were diluted to 5 ϫ 10 4 CFU per ml, cells were dispensed, and equal volumes of twofold serial dilutions of SPs were applied to 96-well polystyrene plates (100-l total volume in each well) as described above.…”

Section: Fig 2 Ms Analyses Of Sp508a Using Single-stage Esi Ms (Uppmentioning

confidence: 99%

Novel Cyclic Lipodepsipeptide from Pseudomonas syringae pv. lachrymans Strain 508 and Syringopeptin Antimicrobial Activities

Grgurina

Bensaci

Pocsfalvi

et al. 2005

Antimicrob Agents Chemother

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The syringopeptins are a group of antimicrobial cyclic lipodepsipeptides produced by several plant-associated pseudomonads. A novel syringopeptin, SP508, was shown to be produced as two homologs (A and B) by Pseudomonas syringae pv. lachrymans strain 508 from apple and to structurally resemble syringopeptin SP22. SP508 differed from SP22 and other syringopeptins by having three instead of four ␣,␤-unsaturated amino acids and a longer ␤-hydroxy acyl chain. Both SP508 and SP22 displayed growth-inhibitory activities against Mycobacterium smegmatis, other gram-positive bacteria, and yeasts but not against gram-negative bacteria. Structure-activity analyses of the SP508 and SP22 homologs indicated chemical structural features that lead to enhanced antimycobacterial activity by these pseudomonad cyclic lipodepsipeptides.Syringopeptins (SPs) are bacterial secondary metabolites belonging to a class of cyclic lipodepsipeptides produced by certain pathovars of the plant bacterium Pseudomonas syringae (1,2,25,36). Their peptide portions contain either 22 (SP22) or 25 (SP25) amino acids that are predominantly hydrophobic, valine and alanine in particular. About 70% of the chiral residues are of the D configuration, and there are four ␣,␤-unsaturated and two 2,4-diaminobutyric acid residues (2,17,21,30). An N-terminal residue dehydroaminobutyric acid (Dhb) is N acylated by a 3-hydroxylated fatty acid chain containing either 10 or 12 carbon atoms; these two types of chains are designated A and B homologs and are typically the more abundant and less abundant forms, respectively. The C-terminal carboxyl group is esterified by the hydroxyl group of the allo-Thr residue positioned at the distance of 7 residues, thus forming an eightmembered lactone macrocycle. So far, two SP25 and three SP22 forms have been identified. SP25 is produced by P. syringae pv. syringae strains that have been isolated from infected millet (B359), citrus (B427) (2), and wheat (M1) (1) as well as from the wheat pathogen P. syringae pv. atrofaciens (36). An isoform differing in the C-terminal residue, SP25-Phe, was detected in a laurel-infecting strain (30). SP22 is produced by a P. syringae pv. syringae strain isolated from pear (B301) (2), and variants are produced by P. syringae pv. syringae strains from sugar cane (SP[SC]) (21) and bean (SPPhv) (17). Each SP-producing P. syringae strain produces one type of SP together with a smaller, nine-amino-acid-containing cyclic lipodepsipeptide-either syringomycin (13, 32), syringotoxin (3), syringostatin (13), or pseudomycin (5).The SPs are produced in infected plant tissues (12, 15), and they play roles as virulence factors in plant diseases (31). The phytotoxic physiological effects of the SPs were demonstrated with isolated plant mitochondria (10) and tobacco protoplasts (18). Lipid bilayer studies have revealed that the probable mechanism of action involves insertion into target membranes with formation of ion channels and consequent ion imbalances that lead to cell death (9, 18). In addition to their phyto...

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“…Although the action of antibacterial peptides is rapid, it usually needs the time of bacterial cell division to act. This is also true for mycobacteria (23,25).…”

Section: Discussionmentioning

confidence: 78%

“…Hence, it was of interest to see if monocytes or macrophages were sensitive to granulysin peptides. were added to evaluate the cytolytic effects of antimycobacterial peptides (23). Except for C(1-13)M(1-13), no peptide was toxic against U937 macrophages up to 200 g/ml (67 to 100 M, depending on the peptide) (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Conserved Structure and Function in the Granulysin and NK-Lysin Peptide Family

et al. 2005

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Granulysin and NK-lysin are homologous bactericidal proteins with a moderate residue identity (35%), both of which have antimycobacterial activity. Short loop peptides derived from the antimycobacterial domains of granulysin, NK-lysin, and a putative chicken NK-lysin were examined and shown to have comparable antimycobacterial but variable Escherichia coli activities. The known structure of the NK-lysin loop peptide was used to predict the structure of the equivalent peptides of granulysin and chicken NK-lysin by homology modeling. The last two adopted a secondary structure almost identical to that of NK-lysin. All three peptides form very similar three-dimensional (3-D) architectures in which the important basic residues assume the same positions in space. The basic residues in granulysin are arginine, while those in NK-lysin and chicken NK-lysin are a mixture of arginine and lysine. We altered the ratio of arginine to lysine in the granulysin fragment to examine the importance of basic residues for antimycobacterial activity. The alteration of the amino acids reduced the activity against E. coli to a larger extent than that against Mycobacterium smegmatis. In granulysin, the arginines in the loop structure are not crucial for antimycobacterial activity but are important for cytotoxicity. We suggest that the antibacterial domains of the related proteins granulysin, NK-lysin, and chicken NK-lysin have conserved their 3-D structure and their function against mycobacteria.

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In vitro activity of PR-39, a proline-arginine-rich peptide, against susceptible and multi-drug-resistant Mycobacterium tuberculosis

Cited by 80 publications

References 30 publications

Antimicrobial peptides in animals and their role in host defences

Antimicrobial peptides in animals and their role in host defences

Novel Cyclic Lipodepsipeptide from Pseudomonas syringae pv. lachrymans Strain 508 and Syringopeptin Antimicrobial Activities

Conserved Structure and Function in the Granulysin and NK-Lysin Peptide Family

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