scholarly journals Systemic Responses of Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Following Exposure to the Antimicrobial Peptide Cathelicidin-BF Imply Multiple Intracellular Targets

Author(s):  
Cunbao Liu ◽  
Bin Shan ◽  
Jialong Qi ◽  
Yanbing Ma
2015 ◽  
Vol 59 (12) ◽  
pp. 7915-7918 ◽  
Author(s):  
João Pires ◽  
Thissa N. Siriwardena ◽  
Michaela Stach ◽  
Regula Tinguely ◽  
Sara Kasraian ◽  
...  

ABSTRACTThein vitroactivity of the novel antimicrobial peptide dendrimer G3KL was evaluated against 32Acinetobacter baumannii(including 10 OXA-23, 7 OXA-24, and 11 OXA-58 carbapenemase producers) and 35Pseudomonas aeruginosa(including 18 VIM and 3 IMP carbapenemase producers) strains and compared to the activities of standard antibiotics. Overall, both species collections showed MIC50/90values of 8/8 μg/ml and minimum bactericidal concentrations at which 50% or 90% of strains tested are killed (MBC50/90) of 8/8 μg/ml. G3KL is a promising molecule with antibacterial activity against multidrug-resistant and extensively drug-resistantA. baumanniiandP. aeruginosaisolates.


2013 ◽  
Vol 6 (3) ◽  
pp. 179-185 ◽  
Author(s):  
M.A. De Francesco ◽  
G. Ravizzola ◽  
L. Peroni ◽  
C. Bonfanti ◽  
N. Manca

2021 ◽  
Vol 3 (1) ◽  
pp. 20-26
Author(s):  
Suliman Mansour Albalawi ◽  
Abdulrahman K. Al-Asmari ◽  
Syed Rafatullah ◽  
Maysa Mahfoud

  The emergence of antibiotic resistant microorganism strains has become a critical concern in the treatment of infectious diseases and makes the search of an alternative therapy a must. The study was designed to evaluate the in vitro antimicrobial activities of the Moringa peregrina (MP) leave (MPL) and seed (MPS) extracts. Antimicrobial assays were performed using a microplate growth inhibition assay against 11 multidrug-resistant (MDR) strains. Following qualitative analysis, dose-response assays were performed using the MTT colorimetric assay. The results showed a strong correlation between the MPL and MPS extract concentration and growth inhibition (P<0.001). MP extract revealed a remarkable antimicrobial effect and inhibited the growth and survival of MDR pathogens which include Escherichia coli; Pseudomonas aeruginosa; Klebsiella pneumonia; Acinetobacter baumannii; Staphylococcus aureus between (88.6-94.7 %) and between (62.3- 88.7%) against Candida Kefyer; Candida parapsilosis; Candida albicans; Candida glabrata; Aspergillus flavus and Fusarium oxysporum. MIC50 ranging from ≤6.25 to 25 mg/mL. Acinetobacter baumannii and Pseudomonas aeruginosa were the most susceptible to MP extracts (MIC50 < 6.25 mg/mL). These results support the use of MP in Arab traditional medicine as natural antimicrobial agents. Additionally, the use of such naturally occurring adjuvant derived from medicinal plants can be used as an adjuvant with synthetic antibiotics to combat bacterial resistance and to enhance the antibacterial potential. Further studies are recommended on isolation and purification of novel antimicrobial molecules to treat the infections caused by microbes.  


2015 ◽  
Vol 59 (4) ◽  
pp. 2280-2285 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Ronald N. Jones ◽  
David J. Farrell

ABSTRACTRX-P873 is a novel antibiotic from the pyrrolocytosine series which exhibits high binding affinity for the bacterial ribosome and broad-spectrum antibiotic properties. The pyrrolocytosines have shownin vitroactivity against multidrug-resistant Gram-negative and Gram-positive strains of bacteria known to cause complicated urinary tract, skin, and lung infections, as well as sepsis.Enterobacteriaceae(657),Pseudomonas aeruginosa(200), andAcinetobacter baumannii(202) isolates from North America and Europe collected in 2012 as part of a worldwide surveillance program were testedin vitroby broth microdilution using Clinical and Laboratory Standards Institute (CLSI) methodology. RX-P873 (MIC90, 0.5 μg/ml) was >32-fold more active than ceftazidime and inhibited 97.1% and 99.5% ofEnterobacteriaceaeisolates at MIC values of ≤1 and ≤4 μg/ml, respectively. There were only three isolates with an MIC value of >4 μg/ml (all were indole-positiveProtea). RX-P873 (MIC50/90, 2/4 μg/ml) was highly active againstPseudomonas aeruginosaisolates, including isolates which were nonsusceptible to ceftazidime or meropenem. RX-P873 was 2-fold less active againstP. aeruginosathan tobramycin (MIC90, 2 μg/ml; 91.0% susceptible) and colistin (MIC90, 2 μg/ml; 99.5% susceptible) and 2-fold more potent than amikacin (MIC90, 8 μg/ml; 93.5% susceptible) and meropenem (MIC90, 8 μg/ml; 76.0% susceptible). RX-P873, the most active agent againstAcinetobacter baumannii(MIC90, 1 μg/ml), was 2-fold more active than colistin (MIC90, 2 μg/ml; 97.0% susceptible) and 4-fold more active than tigecycline (MIC90, 4 μg/ml). This novel agent merits further exploration of its potential against multidrug-resistant Gram-negative bacteria.


2021 ◽  
Author(s):  
Liping Li ◽  
Francesca Short ◽  
Karl Hassan ◽  
Varsha Naidu ◽  
Alaska Pokhrel ◽  
...  

Abstract Biocides, such as antiseptics and disinfectants, are used ubiquitously for hygiene in households and for life-saving infection control in hospitals. An increasing concern is that the widespread use of biocides may contribute to the emergence and spread of multidrug-resistant bacteria. We performed transposon directed insertion site sequencing (TraDIS) to identify genes and key cellular pathways of the multidrug resistant nosocomial pathogen Acinetobacter baumannii, that affect host fitness during exposure to a panel of ten structurally-diverse and clinically-relevant biocides: silver nitrate, benzalkonium, cetyltrimethylammonium bromide (CTAB), chlorhexidine, triclosan, chloroxylenol, polyvidone iodine, bleach, glutaraldehyde and ethanol. Multiple genes encoding proteins localised either in the cell envelope or in the cytoplasm were shown to affect biocide susceptibility. These proteins are involved in multiple processes including fatty acid biogenesis, multidrug efflux, the tricarboxylic acid cycle, cell respiration and cell division, suggesting that these biocides may have intracellular targets in addition to their known effects on the cell envelope. Based on the importance of cell respiration genes for A. baumannii fitness on biocides, we proposed and confirmed that apart from triclosan, the other 9 biocides at sub-inhibitory concentration can dissipate the membrane potential and lead to A. baumannii tolerance to antibiotics that have intracellular targets. Our results support the concern that residual biocides in clinical or community environments can promote the development of antibiotic resistance in pathogenic bacteria.


2005 ◽  
Vol 4 (2) ◽  
pp. 149-150 ◽  
Author(s):  
Matthew E. Falagas ◽  
Sofia K. Kasiakou ◽  
Argyris Michalopoulos

2021 ◽  
Vol 12 ◽  
Author(s):  
Sung-Pang Chen ◽  
Eric H-L Chen ◽  
Sheng-Yung Yang ◽  
Pin-Shin Kuo ◽  
Hau-Ming Jan ◽  
...  

Searching for new antimicrobials is a pressing issue to conquer the emergence of multidrug-resistant (MDR) bacteria and fungi. Antimicrobial peptides (AMPs) usually have antimicrobial mechanisms different from those of traditional antibiotics and bring new hope in the discovery of new antimicrobials. In addition to antimicrobial activity, stability and target selectivity are important concerns to decide whether an antimicrobial peptide can be applied in vivo. Here, we used a simple de novo designed peptide, pepD2, which contains only three kinds of amino acid residues (W, K, L), as an example to evaluate how the residues and modifications affect the antimicrobial activity against Acinetobacter baumannii, stability in plasma, and toxicity to human HEK293 cells. We found that pepI2 with a Leu→Ile substitution can decrease the minimum bactericidal concentrations (MBC) against A. baumannii by one half (4 μg/mL). A D-form peptide, pepdD2, in which the D-enantiomers replaced the L-enantiomers of the Lys(K) and Leu(L) residues, extended the peptide half-life in plasma by more than 12-fold. PepD3 is 3-residue shorter than pepD2. Decreasing peptide length did not affect antimicrobial activity but increased the IC50 to HEK293 cells, thus increased the selectivity index (SI) between A. baumannii and HEK293 cells from 4.7 to 8.5. The chain length increase of the N-terminal acyl group and the Lys→Arg substitution greatly enhanced the hemolytic activity, hence those modifications are not good for clinical application. Unlike colistin, the action mechanism of our peptides relies on negatively charged lipids rather than lipopolysaccharides. Therefore, not only gram-negative bacteria but also gram-positive bacteria can be killed by our peptides.


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