scholarly journals Inhibition of Pseudomonas aeruginosa Biofilm Formation with Surface Modified Polymeric Nanoparticles

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 55 ◽  
Author(s):  
Tyler Flockton ◽  
Logan Schnorbus ◽  
Agustin Araujo ◽  
Jill Adams ◽  
Maryjane Hammel ◽  
...  

The gram-negative bacterial pathogen Pseudomonas aeruginosa represents a prominent clinical concern. Due to the observed high levels of antibiotic resistance, copious biofilm formation, and wide array of virulence factors produced by these bacteria, new treatment technologies are required. Here, we present the development of a series of P. aeruginosa LecA-targeted polymeric nanoparticles and demonstrate the anti-adhesion and biofilm inhibitory properties of these constructs.

2008 ◽  
Vol 190 (11) ◽  
pp. 3969-3978 ◽  
Author(s):  
Yosuke Tashiro ◽  
Nobuhiko Nomura ◽  
Ryoma Nakao ◽  
Hidenobu Senpuku ◽  
Reiko Kariyama ◽  
...  

ABSTRACT Pseudomonas aeruginosa is an opportunistic bacterial pathogen that is one of the most refractory to therapy when it forms biofilms in the airways of cystic fibrosis patients. To date, studies regarding the production of an immunogenic and protective antigen to inhibit biofilm formation by P. aeruginosa have been superficial. The previously uncharacterized outer membrane protein (OMP) Opr86 (PA3648) of P. aeruginosa is a member of the Omp85 family, of which homologs have been found in all gram-negative bacteria. Here we verify the availability of Opr86 as a protective antigen to inhibit biofilm formation by P. aeruginosa PAO1 and several other isolates. A mutant was constructed in which Opr86 expression could be switched on or off through a tac promoter-controlled opr86 gene. The result, consistent with previous Omp85 studies, showed that Opr86 is essential for viability and plays a role in OMP assembly. Depletion of Opr86 resulted in streptococci-like morphological changes and liberation of excess membrane vesicles. A polyclonal antibody against Opr86 which showed reactivity to PAO1 cells was obtained. The antibody inhibited biofilm formation by PAO1 and the other clinical strains tested. Closer examination of early attachment revealed that cells treated with the antibody were unable to attach to the surface. Our data suggest that Opr86 is a critical OMP and a potential candidate as a protective antigen against biofilm formation by P. aeruginosa.


Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1134
Author(s):  
Márió Gajdács ◽  
Zoltán Baráth ◽  
Krisztina Kárpáti ◽  
Dóra Szabó ◽  
Donatella Usai ◽  
...  

Pseudomonas aeruginosa (P. aeruginosa) possesses a plethora of virulence determinants, including the production of biofilm, pigments, exotoxins, proteases, flagella, and secretion systems. The aim of our present study was to establish the relationship between biofilm-forming capacity, the expression of some important virulence factors, and the multidrug-resistant (MDR) phenotype in P. aeruginosa. A total of three hundred and two (n = 302) isolates were included in this study. Antimicrobial susceptibility testing and phenotypic detection of resistance determinants were carried out; based on these results, isolates were grouped into distinct resistotypes and multiple antibiotic resistance (MAR) indices were calculated. The capacity of isolates to produce biofilm was assessed using a crystal violet microtiter-plate based method. Motility (swimming, swarming, and twitching) and pigment-production (pyoverdine and pyocyanin) were also measured. Pearson correlation coefficients (r) were calculated to determine for antimicrobial resistance, biofilm-formation, and expression of other virulence factors. Resistance rates were the highest for ceftazidime (56.95%; n = 172), levofloxacin (54.97%; n = 166), and ciprofloxacin (54.64%; n = 159), while lowest for colistin (1.66%; n = 5); 44.04% (n = 133) of isolates were classified as MDR. 19.87% (n = 60), 20.86% (n = 63) and 59.27% (n = 179) were classified as weak, moderate, and strong biofilm producers, respectively. With the exception of pyocyanin production (0.371 ± 0.193 vs. non-MDR: 0.319 ± 0.191; p = 0.018), MDR and non-MDR isolates did not show significant differences in expression of virulence factors. Additionally, no relevant correlations were seen between the rate of biofilm formation, pigment production, or motility. Data on interplay between the presence and mechanisms of drug resistance with those of biofilm formation and virulence is crucial to address chronic bacterial infections and to provide strategies for their management.


2021 ◽  
Vol 12 ◽  
Author(s):  
Dan Yang ◽  
Suqi Hao ◽  
Ling Zhao ◽  
Fei Shi ◽  
Gang Ye ◽  
...  

With the prevalence of multidrug-resistant bacteria and clinical -acquired pathogenic infections, the development of quorum-sensing (QS) interfering agents is one of the most potential strategies to combat bacterial infections and antibiotic resistance. Chinese herbal medicines constitute a valuable bank of resources for the identification of QS inhibitors. Accordingly, in this research, some compounds were tested for QS inhibition using indicator strains. Paeonol is a phenolic compound, which can effectively reduce the production of violacein without affecting its growth in Chromobacterium violaceum ATCC 12472, indicating its excellent anti-QS activity. This study assessed the anti-biofilm activity of paeonol against Gram-negative pathogens and investigated the effect of paeonol on QS-regulated virulence factors in Pseudomonas aeruginosa. A Caenorhabditis elegans infection model was used to explore the anti-infection ability of paeonol in vivo. Paeonol exhibited an effective anti-biofilm activity against Gram-negative bacteria. The ability of paeonol to interfere with the AHL-mediated quorum sensing systems of P. aeruginosa was determined, found that it could attenuate biofilm formation, and synthesis of pyocyanin, protease, elastase, motility, and AHL signaling molecule in a concentration- and time-dependent manner. Moreover, paeonol could significantly downregulate the transcription level of the QS-related genes of P. aeruginosa including lasI/R, rhlI/R, pqs/mvfR, as well as mediated its virulence factors, lasA, lasB, rhlA, rhlC, phzA, phzM, phzH, and phzS. In vivo studies revealed that paeonol could reduce the pathogenicity of P. aeruginosa and enhance the survival rate of C. elegans, showing a moderate protective effect on C. elegans. Collectively, these findings suggest that paeonol attenuates bacterial virulence and infection of P. aeruginosa and that further research elucidating the anti-QS mechanism of this compound in vivo is warranted.


Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 170
Author(s):  
Angela França ◽  
Vânia Gaio ◽  
Nathalie Lopes ◽  
Luís D. R. Melo

Coagulase-negative staphylococci (CoNS) have emerged as major pathogens in healthcare-associated facilities, being S. epidermidis, S. haemolyticus and, more recently, S. lugdunensis, the most clinically relevant species. Despite being less virulent than the well-studied pathogen S. aureus, the number of CoNS strains sequenced is constantly increasing and, with that, the number of virulence factors identified in those strains. In this regard, biofilm formation is considered the most important. Besides virulence factors, the presence of several antibiotic-resistance genes identified in CoNS is worrisome and makes treatment very challenging. In this review, we analyzed the different aspects involved in CoNS virulence and their impact on health and food.


2016 ◽  
Vol 4 (2) ◽  
Author(s):  
Bhavani Manivannan ◽  
Niranjana Mahalingam ◽  
Sudhir Jadhao ◽  
Amrita Mishra ◽  
Pravin Nilawe ◽  
...  

We present the draft genome assembly of an extensively drug-resistant (XDR) Pseudomonas aeruginosa strain isolated from a patient with a history of genito urinary tuberculosis. The draft genome is 7,022,546 bp with a G+C content of 65.48%. It carries 7 phage genomes, genes for quorum sensing, biofilm formation, virulence, and antibiotic resistance.


2004 ◽  
Vol 186 (9) ◽  
pp. 2880-2890 ◽  
Author(s):  
Isabelle Vallet ◽  
Stephen P. Diggle ◽  
Rachael E. Stacey ◽  
Miguel Cámara ◽  
Isabelle Ventre ◽  
...  

ABSTRACT Pseudomonas aeruginosa is an opportunistic bacterial pathogen which poses a major threat to long-term-hospitalized patients and individuals with cystic fibrosis. The capacity of P. aeruginosa to form biofilms is an important requirement for chronic colonization of human tissues and for persistence in implanted medical devices. Various stages of biofilm formation by this organism are mediated by extracellular appendages, such as type IV pili and flagella. Recently, we identified three P. aeruginosa gene clusters that were termed cup (chaperone-usher pathway) based on their sequence relatedness to the chaperone-usher fimbrial assembly pathway in other bacteria. The cupA gene cluster, but not the cupB or cupC cluster, is required for biofilm formation on abiotic surfaces. In this study, we identified a gene (mvaT) encoding a negative regulator of cupA expression. Such regulatory control was confirmed by several approaches, including lacZ transcriptional fusions, Northern blotting, and transcriptional profiling using DNA microarrays. MvaT also represses the expression of the cupB and cupC genes, although the extent of the regulatory effect is not as pronounced as with cupA. Consistent with this finding, mvaT mutants exhibit enhanced biofilm formation. Although the P. aeruginosa genome contains a highly homologous gene, mvaU, the repression of cupA genes is MvaT specific. Thus, MvaT appears to be an important regulatory component within a complex network that controls biofilm formation and maturation in P. aeruginosa.


2021 ◽  
Author(s):  
Zhexian Liu ◽  
Sarzana S. Hossain ◽  
Zayda Morales Moreira ◽  
Cara H. Haney

Pseudomonas aeruginosa , an opportunistic bacterial pathogen can synthesize and catabolize a number of small cationic molecules known as polyamines. In several clades of bacteria polyamines regulate biofilm formation, a lifestyle-switching process that confers resistance to environmental stress. The polyamine putrescine and its biosynthetic precursors, L-arginine and agmatine, promote biofilm formation in Pseudomonas spp. However, it remains unclear whether the effect is a direct effect of polyamines or through a metabolic derivative. Here we used a genetic approach to demonstrate that putrescine accumulation, either through disruption of the spermidine biosynthesis pathway or the catabolic putrescine aminotransferase pathway, promoted biofilm formation in P. aeruginosa . Consistent with this observation, exogenous putrescine robustly induced biofilm formation in P. aeruginosa that was dependent on putrescine uptake and biosynthesis pathways. Additionally, we show that L-arginine, the biosynthetic precursor of putrescine, also promoted biofilm formation, but via a mechanism independent of putrescine or agmatine conversion. We found that both putrescine and L-arginine induced a significant increase in the intracellular level of bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) (c-di-GMP), a bacterial second messenger widely found in Proteobacteria that upregulates biofilm formation. Collectively these data show that putrescine and its metabolic precursor arginine promote biofilm and c-di-GMP synthesis in P. aeruginosa . Importance: Biofilm formation allows bacteria to physically attach to a surface, confers tolerance to antimicrobial agents, and promotes resistance to host immune responses. As a result, regulation of biofilm is often crucial for bacterial pathogens to establish chronic infections. A primary mechanism of biofilm promotion in bacteria is the molecule c-di-GMP, which promotes biofilm formation. The level of c-di-GMP is tightly regulated by bacterial enzymes. In this study, we found that putrescine, a small molecule ubiquitously found in eukaryotic cells, robustly enhances P. aeruginosa biofilm and c-di-GMP. We propose that P. aeruginosa may sense putrescine as a host-associated signal that triggers a lifestyle switching that favors chronic infection.


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