scholarly journals Hypertonic glucose inhibits growth and attenuates virulence factors of multidrug-resistant Pseudomonas aeruginosa

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Tao Chen ◽  
Ye Xu ◽  
Wenya Xu ◽  
Wenli Liao ◽  
Chunquan Xu ◽  
...  
2020 ◽  
Author(s):  
Tao Chen ◽  
Ye Xu ◽  
Wenya Xu ◽  
Wenli Liao ◽  
Chunquan Xu ◽  
...  

Abstract Background: Pseudomonas aeruginosa is the most common Gram-negative pathogen responsible for chronic wound infections, such as diabetic foot infections, and further exacerbates the treatment options and cost of such conditions. Hypertonic glucose, a commonly used prolotherapy solution, can accelerate the proliferation of granulation tissue and improve microcirculation in wounds. However, the action of hypertonic glucose on bacterial pathogens that infect wounds is unclear. In this study, we investigated the inhibitory effects of hypertonic glucose on multidrug-resistant P. aeruginosa strains isolated from diabetic foot infections. Hypertonic glucose represents a novel approach to control chronic wound infections caused by P. aeruginosa. Results: Four multidrug-resistant P. aeruginosa clinical strains isolated from diabetic foot ulcers from a tertiary hospital in China and the reference P. aeruginosa PAO1 strain were studied. Hypertonic glucose significantly inhibited the growth, biofilm formation, and swimming motility of P. aeruginosa clinical strains and PAO1. Furthermore, hypertonic glucose significantly reduced the production of pyocyanin and elastase virulence factors in P. aeruginosa. The expression of major quorum sensing genes (lasI, lasR, rhlI, and rhlR) in P. aeruginosa were all downregulated in response to hypertonic glucose treatment. In a Galleria mellonella larvae infection model, the administration of hypertonic glucose was shown to increase the survival rates of larvae infected by P. aeruginosa strains (3/5).Conclusions: Hypertonic glucose inhibited the growth, biofilm formation, and swimming motility of P. aeruginosa, as well as reduced the production of virulence factors and quorum sensing gene expression. Further studies that investigate hypertonic glucose therapy should be considered in treating chronic wound infections.


2020 ◽  
Author(s):  
Tao Chen ◽  
Ye Xu ◽  
Wenya Xu ◽  
Wenli Liao ◽  
Chunquan Xu ◽  
...  

Abstract Background: Pseudomonas aeruginosa is the most common Gram-negative pathogen responsible for chronic wound infections such as diabetic foot infections, which make chronic wound treatment become increasingly difficult and costly, further exacerbated. Hypertonic glucose, a commonly used prolotherapy solution, can accelerate the proliferation of granulation tissue and improve microcirculation in the wound, but the knowledge of the impacts that hypertonic glucose has on wound infecting pathogens has lagged. In this study, we aim to investigate the inhibitory effects of hypertonic glucose on diabetic foot infecting multidrug-resistant P. aeruginosa, to offer a novel approach to control the chronic wound infections caused by P. aeruginosa. Results: Four multidrug-resistant P. aeruginosa clinical strains isolated from diabetic foot ulcers from a tertiary hospital in China and P. aeruginosa PAO1 were studied. Hypertonic glucose had a remarkable inhibitory effect on growth of PAO1 and multidrug-resistant P. aeruginosa strains. Furthermore, hypertonic glucose significantly inhibited the formation of biofilm, the ability of swimming, and the production of virulence factors including pyocyanin and elastase in all P. aeruginosa strains. We examined the expressions of major quorum sensing related genes (lasI, lasR, rhlI, and rhlR) in P.aeruginosa and found these genes were all downregulated after hypertonic glucose treatment. In infection model of Galleria mellonella larvae, groups inoculated with P. aeruginosa strains which were treated with hypertonic glucose showed no increased survival rate than non-hypertonic glucose-treated groups. Conclusions: Our research suggested that hypertonic glucose displayed the ability to inhibit growth, biofilm formation and swimming motility as well as attenuate virulence factors of multidrug-resistant P. aeruginosa via regulating quorum sensing system. Further clinical studies combining hypertonic glucose with traditional antibiotics should be considered in chronic wound infections.


2020 ◽  
Author(s):  
Tao Chen ◽  
Ye Xu ◽  
Wenya Xu ◽  
Wenli Liao ◽  
Chunquan Xu ◽  
...  

Abstract Background: Pseudomonas aeruginosa is the most common Gram-negative pathogen responsible for chronic wound infections, such as diabetic foot infections, and further exacerbates the treatment options and cost of such conditions. Hypertonic glucose, a commonly used prolotherapy solution, can accelerate the proliferation of granulation tissue and improve microcirculation in wounds. However, the action of hypertonic glucose on bacterial pathogens that infect wounds is unclear. In this study, we investigated the inhibitory effects of hypertonic glucose on multidrug-resistant P. aeruginosa strains isolated from diabetic foot infections. Hypertonic glucose represents a novel approach to control chronic wound infections caused by P. aeruginosa. Results: Four multidrug-resistant P. aeruginosa clinical strains isolated from diabetic foot ulcers from a tertiary hospital in China and the model P. aeruginosa PAO1 strain were studied. Hypertonic glucose significantly inhibited the growth, biofilm formation, and swimming motility of P. aeruginosa clinical strains and PAO1. Furthermore, hypertonic glucose significantly reduced the production of pyocyanin and elastase virulence factors in P. aeruginosa. The expression of major quorum sensing genes (lasI, lasR, rhlI, and rhlR) in P. aeruginosa were all downregulated in response to hypertonic glucose treatment. In a Galleria mellonella larvae infection model, the administration of hypertonic glucose was shown to increase the survival rates of larvae infected by P. aeruginosa strains (3/5).Conclusions: Hypertonic glucose inhibited the growth, biofilm formation, and swimming motility of P. aeruginosa, as well as reduced the production of virulence factors and quorum sensing gene expression. Further studies that investigate hypertonic glucose therapy should be considered in treating chronic wound infections.


2019 ◽  
Vol 10 (9) ◽  
pp. 5759-5767
Author(s):  
Wan-Ting Lee ◽  
Boon-Khai Tan ◽  
Su-Anne Eng ◽  
Gan Chee Yuen ◽  
Kit Lam Chan ◽  
...  

A strategy to circumvent the problem of multidrug resistant pathogens is the discovery of anti-infectives targeting bacterial virulence or host immunity.


2017 ◽  
Vol 66 (4) ◽  
pp. 427-431 ◽  
Author(s):  
Tomasz Bogiel ◽  
Aleksander Deptuła ◽  
Joanna Kwiecińska-Piróg ◽  
Małgorzata Prażyńska ◽  
Agnieszka Mikucka ◽  
...  

Pseudomonas aeruginosa rods are one of the most commonly isolated microorganisms from clinical specimens, usually responsible for nosocomial infections. Antibiotic-resistant P. aeruginosa strains may present reduced expression of virulence factors. This fact may be caused by appropriate genome management to adapt to changing conditions of the hospital environment. Virulence factors genes may be replaced by those crucial to survive, like antimicrobial resistance genes. The aim of this study was to evaluate, using PCR, the occurrence of exoenzyme S-coding gene (exoS) in two distinct groups of P. aeruginosa strains: 83 multidrug-sensitive (MDS) and 65 multidrug-resistant (MDR) isolates. ExoS gene was noted in 72 (48.7%) of the examined strains: 44 (53.0%) MDS and 28 (43.1%) MDR. The observed differences were not statistically significant (p = 0.1505). P. aeruginosa strains virulence is rather determined by the expression regulation of the possessed genes than the difference in genes frequency amongst strains with different antimicrobial susceptibility patterns.


2021 ◽  
Vol 12 ◽  
Author(s):  
Dejing Shang ◽  
Xue Han ◽  
Wanying Du ◽  
Zhiru Kou ◽  
Fengquan Jiang

Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence, biofilm formation and antibiotic efflux pump expression. The development of effective small molecules targeting the QS system and biofilm formation represents a novel attractive strategy. In this present study, the effects of a series of Trp-containing peptides on the QS-regulated virulence and biofilm development of multidrug-resistant P. aeruginosa, as well as their synergistic antibacterial activity with three classes of traditional chemical antibiotics were investigated. The results showed that Trp-containing peptides at low concentrations reduced the production of QS-regulated virulence factors by downregulating the gene expression of both the las and rhl systems in the strain MRPA0108. Biofilm formation was inhibited in a concentration-dependent manner, which was associated with extracellular polysaccharide production inhibition by downregulating pelA, algD, and pslA transcription. These changes correlated with alterations in the extracellular production of pseudomonal virulence factors and swarming motility. In addition, the combination of Trp-containing peptides at low concentration with the antibiotics ceftazidime and piperacillin provided synergistic effects. Notably, L11W and L12W showed the highest synergy with ceftazidime and piperacillin. A mechanistic study demonstrated that the Trp-containing peptides, especially L12W, significantly decreased β-lactamase activity and expression of efflux pump genes OprM, MexX, and MexA, resulting in a reduction in antibiotic efflux from MRPA0108 cells and thus increasing the antibacterial activity of these antibiotics against MRPA0108.


2020 ◽  
Vol 15 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Liyun Wang ◽  
Chuankai Xia ◽  
Yajun Guo ◽  
Chunjun Yang ◽  
Cheng Cheng ◽  
...  

Aim: The global of spread multidrug-resistant Pseudomonas aeruginosa has become a public health threat. Cold atmospheric plasma (CAP) is reported to have bactericidal efficacy; however, its effects on clinical super multidrug-resistant P. aeruginosa are unclear. The aim of this study was to investigate the bactericidal efficacy of CAP on a strain of super multidrug-resistant P. aeruginosa. Materials & methods: The effects of CAP treatments were evaluated using assays for the detection of growth, viability, metabolism, virulence factors and reactive oxygen species (ROS) levels. Results: Both CAP treatments dose-dependently inhibited cell viability and metabolic activity, and decreased the expression of several virulence factors. CAP treatment induced a significant increase in intracellular ROS levels, and ROS scavengers inhibited this effect. Conclusion: CAP treatment is a promising option for the clinical inhibition of multidrug-resistant P. aeruginosa, and the development of CAP technologies might be the key to solving the long-standing problem of drug-resistant bacteria.


2019 ◽  
Vol 20 (5) ◽  
pp. 471-487 ◽  
Author(s):  
Anna Clara M. Galdino ◽  
Matheus P. de Oliveira ◽  
Teodorico C. Ramalho ◽  
Alexandre A. de Castro ◽  
Marta H. Branquinha ◽  
...  

Pseudomonas aeruginosa is a non-fermentative, gram-negative bacterium that is one of the most common pathogens responsible for hospital-acquired infections worldwide. The management of the infections caused by P. aeruginosa represents a huge challenge in the healthcare settings due to the increased emergence of resistant isolates, some of them resistant to all the currently available antimicrobials, which results in elevated morbimortality rates. Consequently, the development of new therapeutic strategies against multidrug-resistant P. aeruginosa is urgent and needful. P. aeruginosa is wellrecognized for its extreme genetic versatility and its ability to produce a lush variety of virulence factors. In this context, pseudolysin (or elastase B) outstands as a pivotal virulence attribute during the infectious process, playing multifunctional roles in different aspects of the pathogen-host interaction. This protein is a 33-kDa neutral zinc-dependent metallopeptidase that is the most abundant peptidase found in pseudomonal secretions, which contributes to the invasiveness of P. aeruginosa due to its ability to cleave several extracellular matrix proteins and to disrupt the basolateral intercellular junctions present in the host tissues. Moreover, pseudolysin makes P. aeruginosa able to overcome host defenses by the hydrolysis of many immunologically relevant molecules, including antibodies and complement components. The attenuation of this striking peptidase therefore emerges as an alternative and promising antivirulence strategy to combat antibiotic-refractory infections caused by P. aeruginosa. The anti-virulence approach aims to disarm the P. aeruginosa infective arsenal by inhibiting the expression/activity of bacterial virulence factors in order to reduce the invasiveness of P. aeruginosa, avoiding the emergence of resistance since the proliferation is not affected. This review summarizes the most relevant features of pseudolysin and highlights this enzyme as a promising target for the development of new anti-virulence compounds.


Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 260 ◽  
Author(s):  
Syed Ghazanfar Ali ◽  
Mohammad Azam Ansari ◽  
Mohammad A. Alzohairy ◽  
Mohammad N. Alomary ◽  
Mohammad Jalal ◽  
...  

Synthesis of nanoparticles using the plants has several advantages over other methods due to the environmentally friendly nature of plants. Besides being environmentally friendly, the synthesis of nanoparticles using plants or parts of the plants is also cost effective. The present study focuses on the biosynthesis of zinc oxide nanoparticles (ZnO NPs) using the seed extract of Butea monsoperma and their effect on to the quorum-mediated virulence factors of multidrug-resistant clinical isolates of Pseudomonas aeruginosa at sub minimum inhibitory concentration (MIC). The synthesized ZnO NPs were characterized by different techniques, such as Fourier transform infra-red spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), and transmission electron microscopy (TEM). The average size of the nanoparticles was 25 nm as analyzed by TEM. ZnO NPs at sub MIC decreased the production of virulence factors such as pyocyanin, protease and hemolysin for P. aeruginosa (p ≤ 0.05). The interaction of NPs with the P. aeruginosa cells on increasing concentration of NPs at sub MIC levels showed greater accumulation of nanoparticles inside the cells as analyzed by TEM.


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