scholarly journals Subinhibitory concentrations of the cationic antimicrobial peptide colistin induce the pseudomonas quinolone signal in Pseudomonas aeruginosa

Microbiology ◽  
2009 ◽  
Vol 155 (9) ◽  
pp. 2826-2837 ◽  
Author(s):  
Joanne Cummins ◽  
F. Jerry Reen ◽  
Christine Baysse ◽  
Marlies J. Mooij ◽  
Fergal O'Gara

Colistin is an important cationic antimicrobial peptide (CAMP) in the fight against Pseudomonas aeruginosa infection in cystic fibrosis (CF) lungs. The effects of subinhibitory concentrations of colistin on gene expression in P. aeruginosa were investigated by transcriptome and functional genomic approaches. Analysis revealed altered expression of 30 genes representing a variety of pathways associated with virulence and bacterial colonization in chronic infection. These included response to osmotic stress, motility, and biofilm formation, as well as genes associated with LPS modification and quorum sensing (QS). Most striking was the upregulation of Pseudomonas quinolone signal (PQS) biosynthesis genes, including pqsH, pqsB and pqsE, and the phenazine biosynthesis operon. Induction of this central component of the QS network following exposure to subinhibitory concentrations of colistin may represent a switch to a more robust population, with increased fitness in the competitive environment of the CF lung.

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2189
Author(s):  
Hamzah Basil Mohammed ◽  
Sajjad Mohsin I. Rayyif ◽  
Carmen Curutiu ◽  
Alexandra Catalina Birca ◽  
Ovidiu-Cristian Oprea ◽  
...  

Efficient antibiotics to cure Pseudomonas aeruginosa persistent infections are currently insufficient and alternative options are needed. A promising lead is to design therapeutics able to modulate key phenotypes in microbial virulence and thus control the progression of the infectious process without selecting resistant mutants. In this study, we developed a nanostructured system based on Fe3O4 nanoparticles (NPs) and eugenol, a natural plant-compound which has been previously shown to interfere with microbial virulence when utilized in subinhibitory concentrations. The obtained functional NPs are crystalline, with a spherical shape and 10–15 nm in size. The subinhibitory concentrations (MIC 1/2) of the eugenol embedded magnetite NPs (Fe3O4@EUG) modulate key virulence phenotypes, such as attachment, biofilm formation, persister selection by ciprofloxacin, and the production of soluble enzymes. To our knowledge, this is the first report on the ability of functional magnetite NPs to modulate P. aeruginosa virulence and phenotypic resistance; our data highlights the potential of these bioactive nanostructures to be used as anti-pathogenic agents.


2007 ◽  
Vol 60 (3) ◽  
pp. 669-672 ◽  
Author(s):  
Berthony Deslouches ◽  
Ivan A. Gonzalez ◽  
Dilhari DeAlmeida ◽  
Kazi Islam ◽  
Chad Steele ◽  
...  

2014 ◽  
Vol 1 (2) ◽  
pp. 123 ◽  
Author(s):  
Jennifer Borcherding ◽  
Jonas Baltrusaitis ◽  
Haihan Chen ◽  
Larissa Stebounova ◽  
Chia-Ming Wu ◽  
...  

2020 ◽  
Vol 75 (11) ◽  
pp. 3248-3259 ◽  
Author(s):  
Qi Yin ◽  
Siwen Wu ◽  
Lei Wu ◽  
Zhenling Wang ◽  
Yandong Mu ◽  
...  

Abstract Background Antimicrobial peptides are promising alternative antimicrobial agents to combat MDR. DP7, an antimicrobial peptide designed in silico, possesses broad-spectrum antimicrobial activities and immunomodulatory effects. However, the effects of DP7 against Pseudomonas aeruginosa and biofilm infection remain largely unexplored. Objectives To assess (i) the antimicrobial activity of DP7 against MDR P. aeruginosa; and (ii) the antibiofilm activity against biofilm infection. Also, to preliminarily investigate the possible antimicrobial mode of action. Methods The MICs of DP7 for 104 clinical P. aeruginosa strains (including 57 MDR strains) and the antibiofilm activity were determined. RNA-Seq, genome sequencing and cell morphology were conducted. Both acute and chronic biofilm infection mouse models were established. Two mutants, resulting from point mutations associated with LPS and biofilms, were constructed to investigate the potential mode of action. Results DP7, at 8–32 mg/L, inhibited the growth of clinical P. aeruginosa strains and, at 64 mg/L, reduced biofilm formation by 43% to 68% in vitro. In acute lung infection, 0.5 mg/kg DP7 exhibited a 70% protection rate and reduced bacterial colonization by 50% in chronic infection. DP7 mainly suppressed gene expression involving LPS and outer membrane proteins and disrupted cell wall structure. Genome sequencing of the DP7-resistant strain DP7R revealed four SNPs controlling LPS and biofilm production. gshA44 and wbpJ139 mutants displayed LPS reduction and motility deficiency, conferring the reduction of LPS and biofilm biomass of strain DP7R and indicating that LPS was a potential target of DP7. Conclusions These results demonstrate that DP7 may hold potential as an effective antimicrobial agent against MDR P. aeruginosa and related infections.


2008 ◽  
Vol 190 (16) ◽  
pp. 5624-5634 ◽  
Author(s):  
W. James Gooderham ◽  
Manjeet Bains ◽  
Joseph B. McPhee ◽  
Irith Wiegand ◽  
Robert E. W. Hancock

ABSTRACT Pseudomonas aeruginosa is an important opportunistic pathogen that causes infections that can be extremely difficult to treat due to its high intrinsic antibiotic resistance and broad repertoire of virulence factors, both of which are highly regulated. It is demonstrated here that the psrA gene, encoding a transcriptional regulator, was upregulated in response to subinhibitory concentrations of cationic antimicrobial peptides. Compared to the wild type and the complemented mutant, a P. aeruginosa PAO1 psrA::Tn5 mutant displayed intrinsic supersusceptibility to polymyxin B, a last-resort antimicrobial used against multidrug-resistant infections, and the bovine neutrophil antimicrobial peptide indolicidin; this supersusceptibility phenotype correlated with increased outer membrane permeabilization by these agents. The psrA mutant was also defective in simple biofilm formation, rapid attachment, and swarming motility, all of which could be complemented by the cloned psrA gene. The role of PsrA in global gene regulation was studied by comparing the psrA mutant to the wild type by microarray analysis, demonstrating that 178 genes were up- or downregulated ≥2-fold (P ≤ 0.05). Dysregulated genes included those encoding certain known PsrA targets, those encoding the type III secretion apparatus and effectors, adhesion and motility genes, and a variety of metabolic, energy metabolism, and outer membrane permeability genes. This suggests that PsrA might be a key regulator of antimicrobial peptide resistance and virulence.


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