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Chemical Compound Review

Mecillinam     (2R,5R,6S)-6-(azepan-1- ylmethylideneamino)...

Synonyms: Coactin, Selexidin, Hexacillin, MICILLINAM, Mecilinamo, ...
 
 
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Disease relevance of Mecillinam

 

High impact information on Mecillinam

  • The effect of ppGpp is probably mediated by RNA polymerase, since sublethal doses of the polymerase inhibitor rifampicin suppress mecillinam resistance in argS, alaS and ptacrelA'-bearing strains [6].
  • Although the argS and alaS mutants grow slowly, we show that there is no correlation between mecillinam resistance and either growth rate or translation speed [6].
  • Mecillinam, a beta-lactam antibiotic which specifically inactivates penicillin binding protein 2 (PBP2) in Escherichia coli, prevents lateral cell wall elongation, inducing spherical morphology and cell death [6].
  • Furthermore, a ptacrelA' multicopy plasmid makes a wild type strain mecillinam resistant [6].
  • It possesses active PBP2, as evidenced by its rod shape in the absence of mecillinam (but not in its presence), its ability to filament when septation is inhibited, and its penicillin-binding ability [1].
 

Chemical compound and disease context of Mecillinam

 

Biological context of Mecillinam

  • We discuss a possible role for ppGpp as transcriptional activator of cell division genes whose products seem to become limiting in the presence of mecillinam, when cells form large spheres [12].
  • Pharmacokinetics of amdinocillin and pivamdinocillin in normal volunteers [13].
  • Escherichia coli strains partially induced for the stringent response are resistant to mecillinam, a beta-lactam antibiotic which specifically inactivates penicillin-binding protein 2, the key enzyme determining cell shape [12].
  • These results show that the ftsQAZ operon is not the ppGpp target responsible for mecillinam resistance [14].
  • Second, the ppGpp pool was controlled by means of a plasmid carrying a ptac-relA' gene coding for a hyperactive (p)ppGpp synthetase, RelA'; increasing the ppGpp pool by varying the concentration of lac operon inducer IPTG resulted in a sharp threshold ppGpp concentration, above which cells were mecillinam resistant [12].
 

Anatomical context of Mecillinam

  • Mecillinam, a beta-lactam antibiotic which binds specifically to penicillin-binding protein 2 (PBP2), blocks lateral cell-wall elongation, induces spherical morphology and ultimately kills bacteria [1].
  • The lov gene product thus seems to define a link between PBP2 (the mecillinam target) and the ribosomes; we propose that this link is involved in transmitting information on the growth rate (ribosome concentration) to the peptidoglycan synthesizing apparatus [1].
  • The concentration of amdinocillin in the cerebrospinal fluid ranged from approximately 1 to 10 percent of concomitant plasma concentrations [15].
  • Levels of amdinocillin in human plasma and interstitial fluid following intravenous administration [16].
  • Eight patients undergoing lumbar puncture for various neurologic disorders without inflamed meninges received a single dose of 10 mg/kg amdinocillin intravenously [15].
 

Associations of Mecillinam with other chemical compounds

 

Gene context of Mecillinam

 

Analytical, diagnostic and therapeutic context of Mecillinam

References

  1. The Escherichia coli lov gene product connects peptidoglycan synthesis, ribosomes and growth rate. Bouloc, P., Jaffé, A., D'Ari, R. EMBO J. (1989) [Pubmed]
  2. Study of the enhancement of beta-lactam activity by amdinocillin in a model of the human urinary bladder. Anderson, J.D., Eftekhar, F. Am. J. Med. (1983) [Pubmed]
  3. Resistance to mecillinam produced by the co-operative action of mutations affecting lipopolysaccharide, spoT, and cya or crp genes of Salmonella typhimurium. Antón, D.N. Mol. Microbiol. (1995) [Pubmed]
  4. Combination amdinocillin and cefoxitin therapy of multiply-resistant Serratia marcescens urinary tract infections. Ward, T.T., Amon, M.B., Krause, L.K. Am. J. Med. (1983) [Pubmed]
  5. Management of enteric fever with amdinocillin. Ball, A.P., Geddes, A.M. Am. J. Med. (1983) [Pubmed]
  6. Penicillin binding protein 2 is dispensable in Escherichia coli when ppGpp synthesis is induced. Vinella, D., D'Ari, R., Jaffé, A., Bouloc, P. EMBO J. (1992) [Pubmed]
  7. Effect of subinhibitory concentrations of mecillinam on the serum susceptibility of Escherichia coli strains. Taylor, P.W., Gaunt, H., Unger, F.M. Antimicrob. Agents Chemother. (1981) [Pubmed]
  8. Protective effect of amdinocillin against emergence of resistance to ceftazidime in Enterobacter cloacae. Yourassowsky, E., van der Linden, M.P., Lismont, M.J., Crokaert, F., Glupczynski, Y. Antimicrob. Agents Chemother. (1988) [Pubmed]
  9. Activity of semisynthetic penicillins and synergism with mecillinam against Bacteroides species. Trestman, I., Kaye, D., Levison, M.E. Antimicrob. Agents Chemother. (1979) [Pubmed]
  10. Effects of sulfamethizole and amdinocillin against Escherichia coli strains (with various susceptibilities) in an ascending urinary tract infection mouse model. Kerrn, M.B., Frimodt-Møller, N., Espersen, F. Antimicrob. Agents Chemother. (2003) [Pubmed]
  11. Leakage of beta-lactamase: a second mechanism for antibiotic potentiation by amdinocillin. Sanders, C.C., Sanders, W.E., Goering, R.V., McCloskey, R.V. Antimicrob. Agents Chemother. (1987) [Pubmed]
  12. ppGpp concentration, growth without PBP2 activity, and growth-rate control in Escherichia coli. Joseleau-Petit, D., Thévenet, D., D'Ari, R. Mol. Microbiol. (1994) [Pubmed]
  13. Pharmacokinetics of amdinocillin and pivamdinocillin in normal volunteers. Neu, H.C., Srinivasan, S., Francke, E.L., Ortiz-Neu, C., Christenson, J.G. Am. J. Med. (1983) [Pubmed]
  14. Analysis of the effect of ppGpp on the ftsQAZ operon in Escherichia coli. Navarro, F., Robin, A., D'Ari, R., Joseleau-Petit, D. Mol. Microbiol. (1998) [Pubmed]
  15. Amdinocillin pharmacokinetics. Simultaneous administration with cephalothin and cerebrospinal fluid penetration. Gambertoglio, J.G., Barriere, S.L., Lin, E.T., Conte, J.E. Am. J. Med. (1983) [Pubmed]
  16. Levels of amdinocillin in human plasma and interstitial fluid following intravenous administration. Tan, J.S., Salstrom, S.J., File, T.M. Am. J. Med. (1983) [Pubmed]
  17. Amdinocillin: use alone or in combination with cefoxitin or carbenicillin-ticarcillin. Lawson, R.D., Estey, E.H., Bodey, G.P. Am. J. Med. (1983) [Pubmed]
  18. Amdinocillin plus cefoxitin versus cefoxitin alone in therapy of mixed soft tissue infections (including diabetic foot infections). File, T.M., Tan, J.S. Am. J. Med. (1983) [Pubmed]
  19. Parenteral amdinocillin for treatment of complicated urinary tract infections. Cox, C.E. Am. J. Med. (1983) [Pubmed]
  20. Synergistic activity of mecillinam in combination with the beta-lactamase inhibitors clavulanic acid and sulbactam. Neu, H.C. Antimicrob. Agents Chemother. (1982) [Pubmed]
  21. Selected amplification of the cell division genes ftsQ-ftsA-ftsZ in Escherichia coli. Vinella, D., Cashel, M., D'Ari, R. Genetics (2000) [Pubmed]
  22. New mre genes mreC and mreD, responsible for formation of the rod shape of Escherichia coli cells. Wachi, M., Doi, M., Okada, Y., Matsuhashi, M. J. Bacteriol. (1989) [Pubmed]
  23. Mutant isolation and molecular cloning of mre genes, which determine cell shape, sensitivity to mecillinam, and amount of penicillin-binding proteins in Escherichia coli. Wachi, M., Doi, M., Tamaki, S., Park, W., Nakajima-Iijima, S., Matsuhashi, M. J. Bacteriol. (1987) [Pubmed]
  24. Systemic infections treated with amdinocillin in combination with other beta-lactam antibiotics. King, J.W., Beam, T.R., Neu, H.C., Smith, L.G. Am. J. Med. (1983) [Pubmed]
  25. Efficacy, pharmacology, and safety of amdinocillin in treatment of neonates. de Louvois, J., Mulhall, A. Am. J. Med. (1983) [Pubmed]
  26. Morphologic changes produced by amdinocillin alone and in combination with beta-lactam antibiotics: in vitro and in vivo. Kramer, M.J., Mauriz, Y.R., Timmes, M.D., Robertson, T.L., Cleeland, R. Am. J. Med. (1983) [Pubmed]
  27. Penicillin-binding proteins and role of amdinocillin in causing bacterial cell death. Neu, H.C. Am. J. Med. (1983) [Pubmed]
 
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