PMID- 28335779
OWN - NLM
STAT- MEDLINE
DCOM- 20170417
LR  - 20181113
IS  - 1476-0711 (Electronic)
IS  - 1476-0711 (Linking)
VI  - 16
IP  - 1
DP  - 2017 Mar 23
TI  - Activity of AMP2041 against human and animal multidrug resistant Pseudomonas 
      aeruginosa clinical isolates.
PG  - 17
LID - 10.1186/s12941-017-0193-1 [doi]
LID - 17
AB  - BACKGROUND: Antimicrobial resistance is a growing threat to public health. 
      Pseudomonas aeruginosa is a relevant pathogen causing human and animal 
      infections, frequently displaying high levels of resistance to commonly used 
      antimicrobials. The increasing difficulty to develop new effective antibiotics 
      have discouraged investment in this area and only a few new antibiotics are 
      currently under development. An approach to overcome antibiotic resistance could 
      be based on antimicrobial peptides since they offer advantages over currently 
      used microbicides. METHODS: The antimicrobial activity of the synthetic peptide 
      AMP2041 was evaluated against 49 P. aeruginosa clinical strains with high levels 
      of antimicrobial resistance, isolated from humans (n = 19) and animals (n = 30). 
      In vitro activity was evaluated by a microdilution assay for lethal dose 90% 
      (LD(90)), while the activity over time was performed by time-kill assay with 
      12.5 microg/ml of AMP2014. Evidences for a direct membrane damage were investigated 
      on P. aeruginosa ATCC 27853 reference strain, on animal isolate PA-VET 38 and on 
      human isolate PA-H 24 by propidium iodide and on P. aeruginosa ATCC 27853 by 
      scanning electron microscopy. RESULTS: AMP2041 showed a dose-dependent activity, 
      with a mean (SEM) LD(90) of 1.69 and 3.3 microg/ml for animal and human strains, 
      respectively. AMP2041 showed microbicidal activity on P. aeruginosa isolates from 
      a patient with cystic fibrosis (CF) and resistance increased from first infection 
      isolate (LD(90) = 0.3 mug/ml) to the mucoid phenotype (LD(90) = 10.4 mug/ml). The 
      time-kill assay showed a time-dependent bactericidal effect of AMP2041 and LD(90) 
      was reached within 20 min for all the strains. The stain-dead assay showed an 
      increasing of membrane permeabilization and SEM analysis revealed holes, dents 
      and bursts throughout bacterial cell wall after 30 min of incubation with 
      AMP2041. CONCLUSIONS: The obtained results assessed for the first time the good 
      antimicrobial activity of AMP2041 on P. aeruginosa strains of human origin, 
      including those deriving from a CF patient. We confirmed the excellent 
      antimicrobial activity of AMP2041 on P. aeruginosa strains derived from dog 
      otitis. We also assessed that AMP2041 antimicrobial activity is linked to changes 
      of the P. aeruginosa cell wall morphology and to the increasing of membrane 
      permeability.
FAU - Cabassi, Clotilde Silvia
AU  - Cabassi CS
AD  - Department of Veterinary Science, University of Parma, Via del Taglio 10, 43126, 
      Parma, Italy.
FAU - Sala, Andrea
AU  - Sala A
AD  - Department of Veterinary Science, University of Parma, Via del Taglio 10, 43126, 
      Parma, Italy.
FAU - Santospirito, Davide
AU  - Santospirito D
AD  - Department of Veterinary Science, University of Parma, Via del Taglio 10, 43126, 
      Parma, Italy.
FAU - Alborali, Giovanni Loris
AU  - Alborali GL
AD  - Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Via 
      Bianchi 7/9, 25124, Brescia, Italy.
FAU - Carretto, Edoardo
AU  - Carretto E
AD  - Arcispedale S. Maria Nuova, Viale Risorgimento 80, 42123, Reggio Emilia, Italy.
FAU - Ghibaudo, Giovanni
AU  - Ghibaudo G
AD  - Clinica Veterinaria Malpensa, Via Marconi 27, 21017, Samarate, VA, Italy.
FAU - Taddei, Simone
AU  - Taddei S
AD  - Department of Veterinary Science, University of Parma, Via del Taglio 10, 43126, 
      Parma, Italy. simone.taddei@unipr.it.
LA  - eng
PT  - Journal Article
DEP - 20170323
PL  - England
TA  - Ann Clin Microbiol Antimicrob
JT  - Annals of clinical microbiology and antimicrobials
JID - 101152152
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Peptides)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*pharmacology
MH  - Cell Membrane/drug effects/ultrastructure
MH  - Cell Wall/drug effects/ultrastructure
MH  - Dogs
MH  - *Drug Resistance, Multiple, Bacterial
MH  - Humans
MH  - Microbial Viability/drug effects
MH  - Microscopy, Electron, Scanning
MH  - Peptides/*pharmacology
MH  - Pseudomonas Infections/*microbiology/*veterinary
MH  - Pseudomonas aeruginosa/*drug effects/isolation & purification
PMC - PMC5364734
OTO - NOTNLM
OT  - Antimicrobial peptide
OT  - Bacterial membrane damage
OT  - Cinical isolates
OT  - Multidrug resistance
OT  - Pseudomonas aeruginosa
EDAT- 2017/03/25 06:00
MHDA- 2017/04/18 06:00
PMCR- 2017/03/23
CRDT- 2017/03/25 06:00
PHST- 2016/07/21 00:00 [received]
PHST- 2017/03/18 00:00 [accepted]
PHST- 2017/03/25 06:00 [entrez]
PHST- 2017/03/25 06:00 [pubmed]
PHST- 2017/04/18 06:00 [medline]
PHST- 2017/03/23 00:00 [pmc-release]
AID - 10.1186/s12941-017-0193-1 [pii]
AID - 193 [pii]
AID - 10.1186/s12941-017-0193-1 [doi]
PST - epublish
SO  - Ann Clin Microbiol Antimicrob. 2017 Mar 23;16(1):17. doi: 
      10.1186/s12941-017-0193-1.