[en] Aminoglycosides are among the most potent antimicrobials to eradicate Pseudomonas aeruginosa. However, the emergence of resistance has clearly led to a shortage of treatment options, especially for critically ill patients. In the search for new antibiotics, we have synthesized derivatives of the small aminoglycoside, neamine. The amphiphilic aminoglycoside 3',4',6-tri-2-naphtylmethylene neamine (3',4',6-tri-2NM neamine) has appeared to be active against sensitive and resistant P. aeruginosa strains as well as Staphylococcus aureus strains (Baussanne et al., 2010). To understand the molecular mechanism involved, we determined the ability of 3',4',6-tri-2NM neamine to alter the protein synthesis and to interact with the bacterial membranes of P. aeruginosa or models mimicking these membranes. Using atomic force microscopy, we observed a decrease of P. aeruginosa cell thickness. In models of bacterial lipid membranes, we showed a lipid membrane permeabilization in agreement with the deep insertion of 3',4',6-tri-2NM neamine within lipid bilayer as predicted by modeling. This new amphiphilic aminoglycoside bound to lipopolysaccharides and induced P. aeruginosa membrane depolarization. All these effects were compared to those obtained with neamine, the disubstituted neamine derivative (3',6-di-2NM neamine), conventional aminoglycosides (neomycin B and gentamicin) as well as to compounds acting on lipid bilayers like colistin and chlorhexidine. All together, the data showed that naphthylmethyl neamine derivatives target the membrane of P. aeruginosa. This should offer promising prospects in the search for new antibacterials against drug- or biocide-resistant strains.
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Bibliography
J.B. Lyczak, C.L. Cannon, and G.B. Pier Establishment of Pseudomonas aeruginosa infection: lessons from a versatile opportunist Microbes. Infect. 2 2000 1051 1060 (Pubitemid 30664219)
J.C. Davies Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and persistence Paediatr. Respir. Rev. 3 2002 128 134 (Pubitemid 35331506)
V.E. Wagner, and B.H. Iglewski P. aeruginosa biofilms in CF infection Clin. Rev. Allergy Immunol. 35 2008 124 134
K.G. Kerr, and A.M. Snelling Pseudomonas aeruginosa: a formidable and ever-present adversary J. Hosp. Infect. 73 2009 338 344
M.D. Obritsch, D.N. Fish, R. MacLaren, and R. Jung National surveillance of antimicrobial resistance in Pseudomonas aeruginosa isolates obtained from intensive care unit patients from 1993 to 2002 Antimicrob. Agents Chemother. 48 2004 4606 4610 (Pubitemid 39577660)
K. Poole Aminoglycoside resistance in Pseudomonas aeruginosa Antimicrob. Agents Chemother. 49 2005 479 487 (Pubitemid 40175650)
A.P. Zavascki, C.G. Carvalhaes, R.C. Picao, and A.C. Gales Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistance mechanisms and implications for therapy Expert. Rev. Anti. Infect. Ther. 8 2010 71 93
T. Strateva, and D. Yordanov Pseudomonas aeruginosa - a phenomenon of bacterial resistance J. Med. Microbiol. 58 2009 1133 1148
M.G. Page, and J. Heim Prospects for the next anti-Pseudomonas drug Curr. Opin. Pharmacol. 9 2009 558 565
J.M. Ogle, D.E. Brodersen, W.M. Clemons, M.J. Tarry, A.P. Carter, and V. Ramakrishnan Recognition of cognate transfer RNA by the 30S ribosomal subunit Science 292 2001 897 902 (Pubitemid 32422480)
J. Wang, J. Li, H.N. Chen, H. Chang, C.T. Tanifum, H.H. Liu, P.G. Czyryca, and C.W. Chang Glycodiversification for the optimization of the kanamycin class aminoglycosides J. Med. Chem. 48 2005 6271 6285 (Pubitemid 41428982)
Y. Xu, H. Jin, Z. Yang, L. Zhang, Q. Wang, M. Li, and L. Zhang Synthesis and evaluation of novel neamine derivatives effectively targeting to RNA Bioorg. Med. Chem. Lett. 19 2009 2103 2106
P. Setny, and J. Trylska Search for novel aminoglycosides by combining fragment-based virtual screening and 3D-QSAR scoring J. Chem. Inf. Model. 49 2009 390 400
B. Francois, R.J. Russell, J.B. Murray, F. Aboul-ela, B. Masquida, Q. Vicens, and E. Westhof Crystal structures of complexes between aminoglycosides and decoding A site oligonucleotides: role of the number of rings and positive charges in the specific binding leading to miscoding Nucleic Acids Res. 33 2005 5677 5690 (Pubitemid 41548834)
J. Haddad, L.P. Kotra, B. Llano-Sotelo, C. Kim, E.F. Azucena Jr., M. Liu, S.B. Vakulenko, C.S. Chow, and S. Mobashery Design of novel antibiotics that bind to the ribosomal acyltransfer site J. Am. Chem. Soc. 124 2002 3229 3237 (Pubitemid 34270361)
N. Minowa, Y. Akiyama, Y. Hiraiwa, K. Maebashi, T. Usui, and D. Ikeda Synthesis and antibacterial activity of novel neamine derivatives Bioorg. Med. Chem. Lett. 16 2006 6351 6354 (Pubitemid 44709895)
A. Venot, E.E. Swayze, R.H. Griffey, and G.J. Boons Disaccharide mimetics of the aminoglycoside antibiotic neamine Chembiochem 5 2004 1228 1236 (Pubitemid 39297253)
S. Bera, G.G. Zhanel, and F. Schweizer Design, synthesis, and antibacterial activities of neomycin-lipid conjugates: polycationic lipids with potent gram-positive activity J. Med. Chem. 51 2008 6160 6164
J. Zhang, K. Keller, J.Y. Takemoto, M. Bensaci, A. Litke, P.G. Czyryca, and C.W. Chang Synthesis and combinational antibacterial study of 5″-modified neomycin J. Antibiot. (Tokyo) 62 2009 539 544
J. Zhang, F.I. Chiang, L. Wu, P.G. Czyryca, D. Li, and C.W. Chang Surprising alteration of antibacterial activity of 5″-modified neomycin against resistant bacteria J. Med. Chem. 51 2008 7563 7573
S. Bera, G.G. Zhanel, and F. Schweizer Antibacterial activity of guanidinylated neomycin B- and kanamycin A-derived amphiphilic lipid conjugates J. Antimicrob Chemother. 65 2010 1224 1227
S. Bera, G.G. Zhanel, and F. Schweizer Antibacterial activities of aminoglycoside antibiotics-derived cationic amphiphiles. Polyol-modified neomycin B-, kanamycin A-, amikacin-, and neamine-based amphiphiles with potent broad spectrum antibacterial activity J. Med. Chem. 53 2010 3626 3631
I. Baussanne, A. Bussiere, S. Halder, C. Ganem-Elbaz, M. Ouberai, M. Riou, J.M. Paris, E. Ennifar, M.P. Mingeot-Leclercq, and J.L. Decout Synthesis and antimicrobial evaluation of amphiphilic neamine derivatives J. Med. Chem. 53 2010 119 127
N. Lomadze, H.J. Schneider, M.T. Albelda, E. Garcia-Espana, and B. Verdejo Dramatic selectivity differences in the association of DNA and RNA models with new ethylene- and propylene diamine derivatives and their copper complexes Org. Biomol. Chem. 4 2006 1755 1759 (Pubitemid 43835195)
J.T. Oh, T.K. Van Dyk, Y. Cajal, P.S. Dhurjati, M. Sasser, and M.K. Jain Osmotic stress in viable Escherichia coli as the basis for the antibiotic response by polymyxin B Biochem. Biophys. Res. Commun. 246 1998 619 623 (Pubitemid 28420907)
J.T. Oh, Y. Cajal, E.M. Skowronska, S. Belkin, J. Chen, T.K. Van Dyk, M. Sasser, and M.K. Jain Cationic peptide antimicrobials induce selective transcription of micF and osmY in Escherichia coli Biochim. Biophys. Acta 1463 2000 43 54 (Pubitemid 30019234)
Y.Q. Xiong, K. Mukhopadhyay, M.R. Yeaman, J. Adler-Moore, and A.S. Bayer Functional interrelationships between cell membrane and cell wall in antimicrobial peptide-mediated killing of Staphylococcus aureus Antimicrob. Agents Chemother. 49 2005 3114 3121 (Pubitemid 41060548)
A. Liechty, J. Chen, and M.K. Jain Origin of antibacterial stasis by polymyxin B in Escherichia coli Biochim. Biophys. Acta 1463 2000 55 64 (Pubitemid 30019235)
M.E. Falagas, and S.K. Kasiakou Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections Clin. Infect. Dis. 40 2005 1333 1341 (Pubitemid 40570245)
R.L. Soon, R.L. Nation, P.G. Hartley, I. Larson, and J. Li Atomic force microscopy investigation of the morphology and topography of colistin-heteroresistant Acinetobacter baumannii strains as a function of growth phase and in response to colistin treatment Antimicrob. Agents Chemother. 53 2009 4979 4986
R.M. Richards, and R.H. Cavill Electron-microscope study of the effect of chlorhexidine on Pseudomonas aeruginosa Microbios 26 1979 85 93 (Pubitemid 11234445)
G. Kampf, and A. Kramer Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs Clin. Microbiol. Rev. 17 2004 863 893 (Pubitemid 39372521)
F. Van Bambeke, M.P. Mingeot-Leclercq, A. Schanck, R. Brasseur, and P.M. Tulkens Alterations in membrane permeability induced by aminoglycoside antibiotics: studies on liposomes and cultured cells Eur. J. Pharmacol. 247 1993 155 168 (Pubitemid 23309996)
E. Riguet, J. Desire, C. Bailly, and J.L. Decout A route for preparing new neamine derivatives targeting HIV-1 TAR RNA Tetrahedron 60 2004 8053 8064 (Pubitemid 39094322)
V. Pokrovskaya, V. Belakhov, M. Hainrichson, S. Yaron, and T. Baasov Design, synthesis, and evaluation of novel fluoroquinolone-aminoglycoside hybrid antibiotics J. Med. Chem. 52 2009 2243 2254
P.J. Sims, A.S. Waggoner, C.H. Wang, and J.F. Hoffman Studies on the mechanism by which cyanine dyes measure membrane potential in red blood cells and phosphatidylcholine vesicles Biochemistry 13 1974 3315 3330
S.B. Hladky, and T.J. Rink Potential difference and the distribution of ions across the human red blood cell membrane; a study of the mechanism by which the fluorescent cation, diS-C3-(5) reports membrane potential J. Physiol. 263 1976 287 319 (Pubitemid 8014950)
M. Maruyama, S. Yamauchi, K. Akiyama, T. Sugahara, T. Kishida, and Y. Koba Antibacterial activity of a virgatusin-related compound Biosci. Biotechnol. Biochem. 71 2007 677 680 (Pubitemid 46481431)
H. Suzuki, Z.Y. Wang, M. Yamakoshi, M. Kobayashi, and T. Nozawa Probing the transmembrane potential of bacterial cells by voltage-sensitive dyes Anal. Sci. 19 2003 1239 1242
M. Wu, E. Maier, R. Benz, and R.E. Hancock Mechanism of interaction of different classes of cationic antimicrobial peptides with planar bilayers and with the cytoplasmic membrane of Escherichia coli Biochemistry 38 1999 7235 7242
S.J. Wood, K.A. Miller, and S.A. David Anti-endotoxin agents. 1. Development of a fluorescent probe displacement method optimized for the rapid identification of lipopolysaccharide-binding agents Comb. Chem. High Throughput Screen 7 2004 239 249 (Pubitemid 38737751)
D.C. Morrison, and D.M. Jacobs Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides Immunochemistry 13 1976 813 818
R.S. Conrad, and H.E. Gilleland Jr. Lipid alterations in cell envelopes of polymyxin-resistant Pseudomonas aeruginosa isolates J. Bacteriol. 148 1981 487 497 (Pubitemid 12218750)
C. Baysse, M. Cullinane, V. Denervaud, E. Burrowes, J.M. Dow, J.P. Morrissey, L. Tam, J.T. Trevors, and F. O'Gara Modulation of quorum sensing in Pseudomonas aeruginosa through alteration of membrane properties Microbiology 151 2005 2529 2542 (Pubitemid 41149776)
G.R. Bartlett Colorimetric assay methods for free and phosphorylated glyceric acids J. Biol. Chem. 234 1959 469 471
J.N. Weinstein, S. Yoshikami, P. Henkart, R. Blumenthal, and W.A. Hagins Liposome-cell interaction: transfer and intracellular release of a trapped fluorescent marker Science 195 1977 489 492
L. Lins, R. Brasseur, and W.J. Malaisse Conformational analysis of non-sulfonylurea hypoglycemic agents of the meglitinide family Biochem. Pharmacol. 50 1995 1879 1884 (Pubitemid 26011397)
R. Brasseur TAMMO: theoretical analysis of membrane molecular organization R. Brasseur, Molecular Description of Biological Components by Computer-Aided Conformational Analysis 1990 CRC Press Boca Raton 203 219
L. Lins, and R. Brasseur The hydrophobic effect in protein folding FASEB J. 9 1995 535 540
P. Ducarme, M. Rahman, and R. Brasseur IMPALA: a simple restraint field to simulate the biological membrane in molecular structure studies Proteins 30 1998 357 371 (Pubitemid 28117656)
A. Thomas, O. Bouffioux, D. Geeurickx, and R. Brasseur Pex, analytical tools for PDB files. I. GF-Pex: basic file to describe a protein Proteins 43 2001 28 36 (Pubitemid 32194904)
J. Li, R.L. Nation, J.D. Turnidge, R.W. Milne, K. Coulthard, C.R. Rayner, and D.L. Paterson Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections Lancet Infect. Dis. 6 2006 589 601
C.W. Nde, H.J. Jang, F. Toghrol, and W.E. Bentley Global transcriptomic response of Pseudomonas aeruginosa to chlorhexidine diacetate Environ. Sci. Technol. 43 2009 8406 8415
H.C. Neu Aztreonam activity, pharmacology, and clinical uses Am. J. Med. 88 1990 2S 6S
Y.F. Dufrene Towards nanomicrobiology using atomic force microscopy Nat. Rev. Microbiol. 6 2008 674 680
D.J. Muller, J. Helenius, D. Alsteens, and Y.F. Dufrene Force probing surfaces of living cells to molecular resolution Nat. Chem. Biol. 5 2009 383 390
S.A. David, K.A. Balasubramanian, V.I. Mathan, and P. Balaram Analysis of the binding of polymyxin B to endotoxic lipid A and core glycolipid using a fluorescent displacement probe Biochim. Biophys. Acta 1165 1992 147 152
V.M. Bhor, C.J. Thomas, N. Surolia, and A. Surolia Polymyxin B: an ode to an old antidote for endotoxic shock Mol. Biosyst. 1 2005 213 222 (Pubitemid 41442431)
S.A. David Towards a rational development of anti-endotoxin agents: novel approaches to sequestration of bacterial endotoxins with small molecules J. Mol. Recognit. 14 2001 370 387 (Pubitemid 34085333)
J.M. Lopez-Novoa, Y. Quiros, L. Vicente, A.I. MoralesI, and F.J. Lopez-Hernandez New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view Kidney Int. 79 2011 33 45
Y. Chen, W.G. Huang, D.J. Zha, J.H. Qiu, J.L. Wang, S.H. Sha, and J. Schacht Aspirin attenuates gentamicin ototoxicity: from the laboratory to the clinic Hear Res. 226 2007 178 182 (Pubitemid 46428024)
S. Bera, G.G. Zhanel, and F. Schweizer Evaluation of amphiphilic aminoglycoside-peptide triazole conjugates as antibacterial agents Bioorg. Med. Chem. Lett. 20 2010 3031 3035
R.F. Epand, J.E. Pollard, O. Wright, P.B. Savage, and R.M. Epand Depolarization, bacterial membrane composition, and the antimicrobial action of ceragenins Antimicrob. Agents Chemother. 54 2010 3708 3713
O. Domenech, G. Francius, P.M. Tulkens, F. Van Bambeke, Y.F. Dufrene, and M.P. Mingeot-Leclercq Interactions of oritavancin, a new lipoglycopeptide derived from vancomycin, with phospholipid bilayers: effect on membrane permeability and nanoscale lipid membrane organization Biochim. Biophys. Acta 1788 2009 1832 1840
P. Ducarme, M. Rahman, and R. Brasseur IMPALA: a simple restraint field to simulate the biological membrane in molecular structure studies. Proteins 30 1998 357 371 (Pubitemid 28117656)
J.P. Bradshaw, M.J. Darkes, T.A. Harroun, J. Katsaras, and R.M. Epand Oblique membrane insertion of viral fusion peptide probed by neutron diffraction Biochemistry 39 2000 6581 6585 (Pubitemid 30353989)
A. Thomas, M. Allouche, F. Basyn, R. Brasseur, and B. Kerfelec Role of the lid hydrophobicity pattern in pancreatic lipase activity J. Biol. Chem. 280 2005 40074 40083 (Pubitemid 41779142)
L. Lins, B. Charloteaux, C. Heinen, A. Thomas, and R. Brasseur "De novo" design of peptides with specific lipid-binding properties Biophys. J. 90 2006 470 479
H. Bensikaddour, N. Fa, I. Burton, M. Deleu, L. Lins, A. Schanck, R. Brasseur, Y.V. Dufrêne, E. Goormaghtigh, and M.P. Mingeot-Leclercq Characterization of the interactions between fluoroquinolone antibiotics and lipids: a multitechnique approach Biophys. J. 94 2008 3035 3046
R.A. AlTahhan, T.R. Sandrin, A.A. Bodour, and R.M. Maier Rhamnolipid-induced removal of lipopolysaccharide from Pseudomonas aeruginosa: effect on cell surface properties and interaction with hydrophobic substrates Appl. Environ. Microbiol. 66 2000 3262 3268 (Pubitemid 30624566)
S.A. David, S.K. Awasthi, and P. Balaram The role of polar and facial amphipathic character in determining lipopolysaccharide-binding properties in synthetic cationic peptides J. Endotoxin. Res. 6 2000 249 256
S. Snyder, D. Kim, and T.J. McIntosh Lipopolysaccharide bilayer structure: effect of chemotype, core mutations, divalent cations, and temperature Biochemistry 38 1999 10758 10767
M. Vaara New approaches in peptide antibiotics Curr. Opin. Pharmacol. 9 2009 571 576
T. Mogi, and K. Kita Gramicidin S and polymyxins: the revival of cationic cyclic peptide antibiotics Cell Mol. Life Sci. 66 2009 3821 3826
H. Tsubery, I. Ofek, S. Cohen, M. Eisenstein, and M. Fridkin Modulation of the hydrophobic domain of polymyxin B nonapeptide: effect on outer-membrane permeabilization and lipopolysaccharide neutralization Mol. Pharmacol. 62 2002 1036 1042 (Pubitemid 35222493)
H.W. Huang Molecular mechanism of antimicrobial peptides: the origin of cooperativity Biochim. Biophys. Acta 1758 2006 1292 1302 (Pubitemid 44436067)
G.J. Gabriel, A. Som, A.E. Madkour, T. Eren, and G.N. Tew Infectious disease: connecting innate immunity to biocidal polymers Mater. Sci. Eng. R. Rep. 57 2007 28 64 (Pubitemid 47042367)
J.K. Hobbs, K. Miller, A.J. O'Neill, and I. Chopra Consequences of daptomycin-mediated membrane damage in Staphylococcus aureus J. Antimicrob. Chemother. 62 2008 1003 1008
K. Lohner New strategies for novel antibiotics: peptides targeting bacterial cell membranes Gen. Physiol. Biophys. 28 2009 105 116
E. Glukhov, M. Stark, L.L. Burrows, and C.M. Deber Basis for selectivity of cationic antimicrobial peptides for bacterial versus mammalian membranes J. Biol. Chem. 280 2005 33960 33967 (Pubitemid 41443116)
D.L. Higgins, R. Chang, D.V. Debabov, J. Leung, T. Wu, K.M. Krause, E. Sandvik, J.M. Hubbard, K. Kaniga, D.E. Schmidt Jr., Q. Gao, R.T. Cass, D.E. Karr, B.M. Benton, and P.P. Humphrey Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis and cell membrane integrity in methicillin-resistant Staphylococcus aureus Antimicrob. Agents Chemother. 49 2005 1127 1134 (Pubitemid 40327734)
B. Findlay, G.G. Zhanel, and F. Schweizer Cationic amphiphiles, a new generation of antimicrobials inspired by the natural antimicrobial peptide scaffold Antimicrob. Agents Chemother. 54 2010 4049 4058
L. Lins, A. Thomas, and R. Brasseur Analysis of accessible surface of residues in proteins Protein Sci. 12 2003 1406 1417 (Pubitemid 36759345)
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