Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Sep 12;21(9):1223.
doi: 10.3390/molecules21091223.

Synergistic Antipseudomonal Effects of Synthetic Peptide AMP38 and Carbapenems

Affiliations
Free PMC article

Synergistic Antipseudomonal Effects of Synthetic Peptide AMP38 and Carbapenems

Héctor Rudilla et al. Molecules. .
Free PMC article

Abstract

The aim was to explore the antimicrobial activity of a synthetic peptide (AMP38) and its synergy with imipenem against imipenem-resistant Pseudomonas aeruginosa. The main mechanism of imipenem resistance is the loss or alteration of protein OprD. Time-kill and minimal biofilm eradication concentration (MBEC) determinations were carried out by using clinical imipenem-resistant strains. AMP38 was markedly synergistic with imipenem when determined in imipenem-resistant P. aeruginosa. MBEC obtained for the combination of AMP38 and imipenem was of 62.5 μg/mL, whereas the MBEC of each antimicrobial separately was 500 μg/mL. AMP38 should be regarded as a promising antimicrobial to fight MDR P. aeruginosa infections. Moreover, killing effect and antibiofilm activity of AMP38 plus imipenem was much higher than that of colistin plus imipenem.

Keywords: Pseudomonas; antimicrobial peptides; biofilm eradication; synergism.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of the cyclolipopeptide analogue of polymyxin AMP38 (below) and of natural polymyxin B (above). The structural and chemical features modified in the analogue with respect to polymyxin are highlighted in blue.
Figure 2
Figure 2
Antibacterial activity of colistin sulphate (COL), imipenem (IMI), meropenem (MER) and AMP38 in different combinations. (A) ATCC strain; Control (filled circles), IMI 4 μg/mL (open circles), COL 0.5 μg/mL and IMI 4 μg/mL (filled triangles), COL 4 μg/mL (open triangles), COL 4 μg/mL and IMI 0.5 μg/mL (filled squares), COL 4 μg/mL and IMI 4 μg/mL (open squares); (B) PA116136 strain; Control (filled circles), COL 0.25 μg/mL and IMI 32 μg/mL (open circles), COL 2 μg/mL and IMI 4 μg/mL (filled triangles), COL 2 μg/mL and IMI 32 μg/mL (open triangles); (C) PA116136 strain; Control (filled circles), IMI 4 μg/mL (open circles), AMP38 8 μg/mL (filled triangles), AMP38 8 μg/mL and IMI 4 μg/mL (open triangles); (D) PA116136 strain; Control (filled circles), MER 1 μg/mL (open circles), AMP38 8 μg/mL (filled triangles), AMP38 8 μg/mL and MER 1 μg/mL (open triangles); (E) 536SJD strain; Control (filled circles), IMI 4 μg/mL (open circles), AMP38 2 μg/mL (filled triangles), IMI 4 μg/mL and AMP38 2 μg/mL (open triangles); (F) 481SJD strain; Control (filled circles), IMI 4 μg/mL (open circles), AMP38 4 μg/mL (filled triangles), IMI 4 μg/mL and AMP38 4 μg/mL (open triangles).
Figure 3
Figure 3
Growth inhibition by the combination of imipenem and AMP38 at 4 μg/mL of each.
Figure 4
Figure 4
TEM electromicrographs of P. aeruginosa PA116136 (a) untreated and (b) AMP38-treated; and Serratia marcescens NIMA strain (c) untreated and (d) AMP38-treated.

Similar articles

See all similar articles

Cited by 12 articles

See all "Cited by" articles

References

    1. Dosler S., Karaaslan E. Inhibition and destruction of Pseudomonas aeruginosa biofilms by antibiotics and antimicrobial peptides. Peptides. 2014;62:32–37. doi: 10.1016/j.peptides.2014.09.021. - DOI - PubMed
    1. Terzi H.A., Kulah C., Ciftci I.H. The effects of active efflux pumps on antibiotic resistance in Pseudomonas aeruginosa. World J. Microbiol. Biotechnol. 2014;30:2681–2687. doi: 10.1007/s11274-014-1692-2. - DOI - PubMed
    1. Lambert P.A. Mechanisms of antibiotic resistance in Pseudomonas aeruginosa. J. R. Soc. Med. 2002;95(Suppl. S4):22–26. - PMC - PubMed
    1. Pikis A. Decreased susceptibility to imipenem among penicillin-resistant Streptococcus pneumonia. J. Antimicrob. Chemother. 1997;40:105–108. doi: 10.1093/jac/40.1.105. - DOI - PubMed
    1. Zhanel G.G., Simor A.E., Vercaigne L., Mandell L. Imipenem and meropenem: Comparison of in vitro activity, pharmacokinetics, clinical trials and adverse effects. Can. J. Infect. Dis. 1998;9:215–228. doi: 10.1155/1998/831425. - DOI - PMC - PubMed

MeSH terms

Substances

Feedback