scholarly journals Quorum Sensing Inhibitors to Quench P. aeruginosa Pathogenicity

2021 ◽  
Vol 14 (12) ◽  
pp. 1262
Author(s):  
Marine Duplantier ◽  
Elodie Lohou ◽  
Pascal Sonnet

The emergence and the dissemination of multidrug-resistant bacteria constitute a major public health issue. Among incriminated Gram-negative bacteria, Pseudomonas aeruginosa has been designated by the WHO as a critical priority threat. During the infection process, this pathogen secretes various virulence factors in order to adhere and colonize host tissues. Furthermore, P. aeruginosa has the capacity to establish biofilms that reinforce its virulence and intrinsic drug resistance. The regulation of biofilm and virulence factor production of this micro-organism is controlled by a specific bacterial communication system named Quorum Sensing (QS). The development of anti-virulence agents targeting QS that could attenuate P. aeruginosa pathogenicity without affecting its growth seems to be a promising new therapeutic strategy. This could prevent the selective pressure put on bacteria by the conventional antibiotics that cause their death and promote resistant strain survival. This review describes the QS-controlled pathogenicity of P. aeruginosa and its different specific QS molecular pathways, as well as the recent advances in the development of innovative QS-quenching anti-virulence agents to fight anti-bioresistance.

2021 ◽  
Author(s):  
Stephanie Rey ◽  
Nilofar Faruqui ◽  
Alex Hoose ◽  
Camilla Dondi ◽  
Maxim Ryadnov

The emergence of multidrug-resistant bacteria stimulates the search for antimicrobial materials capable of addressing challenges conventional antibiotics fail to address. The ability to target intracellular bacteria remains one of the...


2021 ◽  
Vol 21 ◽  
Author(s):  
Priyanka Ashwath ◽  
Akhila Dharnappa Sannejal

: The increasing resistance of the disease-causing pathogens to antimicrobial drugs is a public health concern and a socio-economic burden. The emergence of multi-drug resistant strains has made it harder to treat and combat infectious diseases with available conventional antibiotics. There are currently few effective therapeutic regimens for the successful prevention of infections caused by drug-resistant microbes. The various alternative strategies used in the recent past to decrease and limit antibiotic resistance in pathogens include bacteriophages, vaccines, anti-biofilm peptides, and antimicrobial peptides. However, in this review, we focus on the novel and robust molecular approach of antisense RNA (asRNA) technology and the clustered regulatory interspaced short palindromic repeat (CRISPR)-based antibiotic therapy, which can be exploited to selectively eradicate the drug-resistant bacterial strain in a sequence-specific fashion establishing opportunities in the treatment of multi-drug resistant related infections.


2021 ◽  
Vol 42 (6supl2) ◽  
pp. 3813-3824
Author(s):  
Rodrigo Pacheco Ornellas ◽  
◽  
Hugo Peralva Lopes ◽  
Daniela de Queiroz Baptista ◽  
Thomas Salles Dias ◽  
...  

Broiler chickens and derived products are a key source of Shiga toxin-producing Escherichia coli (STEC) in humans. This pathotype is responsible for causing severe episodes of diarrhea, which can progress to systemic complications. A rapid and accurate diagnosis of the disease, and early treatment of the infection with antimicrobials, can prevent it worsening. However, multidrug-resistant strains have potentially negative implications for treatment success. In this context, the aim of the present study was to isolate and identify multidrug-resistant STEC strains from broiler chickens and carcasses. Of 171 E. coli strains, isolated by conventional microbiological techniques and submitted to Polymerase Chain Reaction (PCR), for detection of stx1 and stx2 genes, 21.05% (36/171) were STEC pathotype, and most of them (66.67% - 24/36) carried both stx1 and eae genes. The multidrug resistance pattern was observed in 75% (27/36) of STEC strains. The presence of STEC in broiler chickens and carcasses reinforces that these sources may act as reservoirs for this pathotype. Multidrug-resistant bacteria contaminating animal products represent a public health issue because of the possibility of spread of multidrug-resistant determinants in the food chain and a higher risk of failure in human treatment when antimicrobials are needed.


Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 327 ◽  
Author(s):  
Mariana Espinosa-Valdés ◽  
Sara Borbolla-Alvarez ◽  
Ana Delgado-Espinosa ◽  
Juan Sánchez-Tejeda ◽  
Anabelle Cerón-Nava ◽  
...  

Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N-acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa. All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins.


2007 ◽  
Vol 2 (1) ◽  
pp. 1-33 ◽  
Author(s):  
Andrea Giuliani ◽  
Giovanna Pirri ◽  
Silvia Nicoletto

AbstractAntibiotic resistance is increasing at a rate that far exceeds the pace of new development of drugs. Antimicrobial peptides, both synthetic and from natural sources, have raised interest as pathogens become resistant against conventional antibiotics. Indeed, one of the major strengths of this class of molecules is their ability to kill multidrug-resistant bacteria. Antimicrobial peptides are relatively small (6 to 100 aminoacids), amphipathic molecules of variable length, sequence and structure with activity against a wide range of microorganisms including bacteria, protozoa, yeast, fungi, viruses and even tumor cells. They usually act through relatively non-specific mechanisms resulting in membranolytic activity but they can also stimulate the innate immune response. Several peptides have already entered pre-clinical and clinical trials for the treatment of catheter site infections, cystic fibrosis, acne, wound healing and patients undergoing stem cell transplantation. We review the advantages of these molecules in clinical applications, their disadvantages including their low in vivo stability, high costs of production and the strategies for their discovery and optimization.


2015 ◽  
Vol 3 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Tek Raj Awasthi ◽  
Narayan Dutt Pant ◽  
Puspa Raj Dahal

Involvement of multidrug resistant bacteria in causing community acquired infection is very serious public health issue. The main objective of our study was to determine the prevalence of multidrug resistant bacteria in causing community acquired urinary tract infection. In this study we cultured the 384 mid stream urine samples collected aseptically from the patients attending outpatient department of Seti zonal hospital and having no past history of hospitalization. The organisms isolated were identified by using conventional biochemical tests and antimicrobial susceptibility testing was performed by Kirby Bauer disc diffusion technique. Out of total 384 samples 98 (25.52%) samples showed significant bacterial growth. The most prevalent bacterium isolated was Escherichia coli. 42.86% of the bacteria isolated were found to be multidrug resistant (MDR). The involvement of such large numbers of multidrug resistant bacteria in causing community acquired urinary tract infection is very serious issue and cannot be neglected. And some abrupt initiatives should be taken by the responsible authorities to improve or at least avoid the further worsening of the situation.Nepal Journal of Biotechnology. Dec. 2015 Vol. 3, No. 1: 55-59


Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1587
Author(s):  
Feng Wang ◽  
Xiaohang Liu ◽  
Zhengyu Deng ◽  
Yao Zhang ◽  
Xinyu Ji ◽  
...  

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.


2012 ◽  
Vol 57 (1) ◽  
pp. 220-228 ◽  
Author(s):  
Jiexi Yan ◽  
Kairong Wang ◽  
Wen Dang ◽  
Ru Chen ◽  
Junqiu Xie ◽  
...  

ABSTRACTThe extensive use and misuse of antibiotics in medicine result in the emergence of multidrug-resistant bacteria, creating an urgent need for the development of new chemotherapeutic agents. Nowadays, antimicrobial peptides are widely recognized as a class of promising candidates with activity against multidrug-resistant bacteria. NK-18 is a truncated peptide derived from NK-Lysin, an effector of cytotoxic T cells and natural killer cells. In this study, we studied the antibacterial mechanism of action of NK-18. The results revealed that NK-18 has potent antibacterial activity againstEscherichia coliandStaphylococcus aureus. According to our findings, NK-18 is membrane active and its target of action is not only the bacterial membrane but also the DNA in the cytoplasm. The double targets of NK-18 make it difficult for bacteria to generate resistance, which may present a new strategy to defend against multidrug-resistant bacteria and provide a new lead in the design of potent antimicrobial peptides with therapeutic application in the presence of increasing resistance to conventional antibiotics.


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