Focused review on dual inhibition of quorum sensing and efflux pumps: A potential way to combat multi drug resistant Staphylococcus aureus infections

2021 ◽  
Vol 190 ◽  
pp. 33-43
Author(s):  
Bhawandeep Kaur ◽  
Jeena Gupta ◽  
Sarika Sharma ◽  
Divakar Sharma ◽  
Sandeep Sharma
2003 ◽  
Vol 47 (6) ◽  
pp. 1979-1983 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Yael Gov ◽  
Roberto Ghiselli ◽  
Maria Simona Del Prete ◽  
...  

ABSTRACT Staphylococcus aureus is a prevalent cause of bacterial infections associated with indwelling medical devices. RNA III inhibiting peptide (RIP) is known to inhibit S. aureus pathogenesis by disrupting quorum-sensing mechanisms. RIP was tested in the present study for its ability to inhibit S. aureus biofilm formation in a rat Dacron graft model. The activity of RIP was synergistic with those of antibiotics for the complete prevention of drug-resistant S. aureus infections.


2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Eric F. Kong ◽  
Christina Tsui ◽  
Sona Kucharíková ◽  
Patrick Van Dijck ◽  
Mary Ann Jabra-Rizk

ABSTRACT In microbial biofilms, microorganisms utilize secreted signaling chemical molecules to coordinate their collective behavior. Farnesol is a quorum sensing molecule secreted by the fungal species Candida albicans and shown to play a central physiological role during fungal biofilm growth. Our pervious in vitro and in vivo studies characterized an intricate interaction between C. albicans and the bacterial pathogen Staphylococcus aureus, as these species coexist in biofilm. In this study, we aimed to investigate the impact of farnesol on S. aureus survival, biofilm formation, and response to antimicrobials. The results demonstrated that in the presence of exogenously supplemented farnesol or farnesol secreted by C. albicans in biofilm, S. aureus exhibited significantly enhanced tolerance to antimicrobials. By using gene expression studies, S. aureus mutant strains, and chemical inhibitors, the mechanism for the enhanced tolerance was attributed to upregulation of drug efflux pumps. Importantly, we showed that sequential exposure of S. aureus to farnesol generated a phenotype of high resistance to antimicrobials. Based on the presence of intracellular reactive oxygen species upon farnesol exposure, we hypothesize that antimicrobial tolerance in S. aureus may be mediated by farnesol-induced oxidative stress triggering the upregulation of efflux pumps, as part of a general stress response system. Hence, in mixed biofilms, C. albicans may influence the pathogenicity of S. aureus through acquisition of a drug-tolerant phenotype, with important therapeutic implications. Understanding interspecies signaling in polymicrobial biofilms and the specific drug resistance responses to secreted molecules may lead to the identification of novel targets for drug development.


2013 ◽  
Vol 7 (1) ◽  
pp. 72-82 ◽  
Author(s):  
Marta Martins ◽  
Matthew P McCusker ◽  
Miguel Viveiros ◽  
Isabel Couto ◽  
Séamus Fanning ◽  
...  

It is known that bacteria showing a multi-drug resistance phenotype use several mechanisms to overcome the action of antibiotics. As a result, this phenotype can be a result of several mechanisms or a combination of thereof. The main mechanisms of antibiotic resistance are: mutations in target genes (such as DNA gyrase and topoisomerase IV); over-expression of efflux pumps; changes in the cell envelope; down regulation of membrane porins, and modified lipopolysaccharide component of the outer cell membrane (in the case of Gram-negative bacteria). In addition, adaptation to the environment, such as quorum sensing and biofilm formation can also contribute to bacterial persistence. Due to the rapid emergence and spread of bacterial isolates showing resistance to several classes of antibiotics, methods that can rapidly and efficiently identify isolates whose resistance is due to active efflux have been developed. However, there is still a need for faster and more accurate methodologies. Conventional methods that evaluate bacterial efflux pump activity in liquid systems are available. However, these methods usually use common efflux pump substrates, such as ethidium bromide or radioactive antibiotics and therefore, require specialized instrumentation, which is not available in all laboratories. In this review, we will report the results obtained with the Ethidium Bromide-agar Cartwheel method. This is an easy, instrument-free, agar based method that has been modified to afford the simultaneous evaluation of as many as twelve bacterial strains. Due to its simplicity it can be applied to large collections of bacteria to rapidly screen for multi-drug resistant isolates that show an over-expression of their efflux systems. The principle of the method is simple and relies on the ability of the bacteria to expel a fluorescent molecule that is substrate for most efflux pumps, ethidium bromide. In this approach, the higher the concentration of ethidium bromide required to produce fluorescence of the bacterial mass, the greater the efflux capacity of the bacterial cells. We have tested and applied this method to a large number of Gram-positive and Gram-negative bacteria to detect efflux activity among these multi-drug resistant isolates. The presumptive efflux activity detected by the Ethidium Bromide-agar Cartwheel method was subsequently confirmed by the determination of the minimum inhibitory concentration for several antibiotics in the presence and absence of known efflux pump inhibitors.


2014 ◽  
Vol 21 ◽  
pp. 92
Author(s):  
K. Ganguly ◽  
J.L. Phillips ◽  
M.S. Wren ◽  
P.E. Pardington ◽  
S. Gnanakaran ◽  
...  

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 625
Author(s):  
Fatma Y. Ahmed ◽  
Usama Farghaly Aly ◽  
Rehab Mahmoud Abd El-Baky ◽  
Nancy G. F. M. Waly

Most of the infections caused by multi-drug resistant (MDR) P. aeruginosa strains are extremely difficult to be treated with conventional antibiotics. Biofilm formation and efflux pumps are recognized as the major antibiotic resistance mechanisms in MDR P. aeruginosa. Biofilm formation by P. aeruginosa depends mainly on the cell-to-cell communication quorum-sensing (QS) systems. Titanium dioxide nanoparticles (TDN) have been used as antimicrobial agents against several microorganisms but have not been reported as an anti-QS agent. This study aims to evaluate the impact of titanium dioxide nanoparticles (TDN) on QS and efflux pump genes expression in MDR P. aeruginosa isolates. The antimicrobial susceptibility of 25 P. aeruginosa isolates were performed by Kirby–Bauer disc diffusion. Titanium dioxide nanoparticles (TDN) were prepared by the sol gel method and characterized by different techniques (DLS, HR-TEM, XRD, and FTIR). The expression of efflux pumps in the MDR isolates was detected by the determination of MICs of different antibiotics in the presence and absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP). Biofilm formation and the antibiofilm activity of TDN were determined using the tissue culture plate method. The effects of TDN on the expression of QS genes and efflux pump genes were tested using real-time polymerase chain reaction (RT-PCR). The average size of the TDNs was 64.77 nm. It was found that TDN showed a significant reduction in biofilm formation (96%) and represented superior antibacterial activity against P. aeruginosa strains in comparison to titanium dioxide powder. In addition, the use of TDN alone or in combination with antibiotics resulted in significant downregulation of the efflux pump genes (MexY, MexB, MexA) and QS-regulated genes (lasR, lasI, rhll, rhlR, pqsA, pqsR) in comparison to the untreated isolate. TDN can increase the therapeutic efficacy of traditional antibiotics by affecting efflux pump expression and quorum-sensing genes controlling biofilm production.


2021 ◽  
Vol 140 ◽  
pp. 111768
Author(s):  
Janaína Esmeraldo Rocha ◽  
Thiago Sampaio de Freitas ◽  
Jayze da Cunha Xavier ◽  
Raimundo Luiz Silva Pereira ◽  
Francisco Nascimento Pereira Junior ◽  
...  

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 126
Author(s):  
Salvatore Princiotto ◽  
Stefania Mazzini ◽  
Loana Musso ◽  
Fabio Arena ◽  
Sabrina Dallavalle ◽  
...  

The global increase in infections by multi-drug resistant (MDR) pathogens is severely impacting our ability to successfully treat common infections. Herein, we report the antibacterial activity against S. aureus and E. faecalis (including some MDR strains) of a panel of adarotene-related synthetic retinoids. In many cases, these compounds showed, together with favorable MICs, a detectable bactericidal effect. We found that the pattern of substitution on adarotene could be modulated to obtain selectivity for antibacterial over the known anticancer activity of these compounds. NMR experiments allowed us to define the interaction between adarotene and a model of microorganism membrane. Biological assessment confirmed that the scaffold of adarotene is promising for further developments of non-toxic antimicrobials active on MDR strains.


2021 ◽  
Vol 53 (2) ◽  
pp. 149-156
Author(s):  
Fernando Gomes Figueredo ◽  
Rodrigo Emmanuel L. T. Parente ◽  
Maynara Rodrigues Cavalcante-Figueredo ◽  
Jakson Gomes Figueiredo ◽  
Raimundo Luiz Pereira da Silva ◽  
...  

2020 ◽  
Vol 41 (S1) ◽  
pp. s40-s40
Author(s):  
Hsiu Wu ◽  
Tyler Kratzer ◽  
Liang Zhou ◽  
Minn Soe ◽  
Jonathan Edwards ◽  
...  

Background: To provide a standardized, risk-adjusted method for summarizing antimicrobial use (AU), the Centers for Disease Control and Prevention developed the standardized antimicrobial administration ratio, an observed-to-predicted use ratio in which predicted use is estimated from a statistical model accounting for patient locations and hospital characteristics. The infection burden, which could drive AU, was not available for assessment. To inform AU risk adjustment, we evaluated the relationship between the burden of drug-resistant gram-positive infections and the use of anti-MRSA agents. Methods: We analyzed data from acute-care hospitals that reported ≥10 months of hospital-wide AU and microbiologic data to the National Healthcare Safety Network (NHSN) from January 2018 through June 2019. Hospital infection burden was estimated using the prevalence of deduplicated positive cultures per 1,000 admissions. Eligible cultures included blood and lower respiratory specimens that yielded oxacillin/cefoxitin–resistant Staphylococcus aureus (SA) and ampicillin-nonsusceptible enterococci, and cerebrospinal fluid that yielded SA. The anti-MRSA use rate is the total antimicrobial days of ceftaroline, dalbavancin, daptomycin, linezolid, oritavancin, quinupristin/dalfopristin, tedizolid, telavancin, and intravenous vancomycin per 1,000 days patients were present. AU rates were modeled using negative binomial regression assessing its association with infection burden and hospital characteristics. Results: Among 182 hospitals, the median (interquartile range, IQR) of anti-MRSA use rate was 86.3 (59.9–105.0), and the median (IQR) prevalence of drug-resistant gram-positive infections was 3.4 (2.1–4.8). Higher prevalence of drug-resistant gram-positive infections was associated with higher use of anti-MRSA agents after adjusting for facility type and percentage of beds in intensive care units (Table 1). Number of hospital beds, average length of stay, and medical school affiliation were nonsignificant. Conclusions: Prevalence of drug-resistant gram-positive infections was independently associated with the use of anti-MRSA agents. Infection burden should be used for risk adjustment in predicting the use of anti-MRSA agents. To make this possible, we recommend that hospitals reporting to NHSN’s AU Option also report microbiologic culture results.Funding: NoneDisclosures: None


Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 321
Author(s):  
Shekh Sabir ◽  
Tsz Tin Yu ◽  
Rajesh Kuppusamy ◽  
Basmah Almohaywi ◽  
George Iskander ◽  
...  

The quorum sensing (QS) system in multi-drug-resistant bacteria such as P. aeruginosa is primarily responsible for the development of antibiotic resistance and is considered an attractive target for antimicrobial drug discovery. In this study, we synthesised a series of novel selenourea and thiourea-containing dihydropyrrol-2-one (DHP) analogues as LasR antagonists. The selenium DHP derivatives displayed significantly better quorum-sensing inhibition (QSI) activities than the corresponding sulphur analogues. The most potent analogue 3e efficiently inhibited the las QS system by 81% at 125 µM and 53% at 31 µM. Additionally, all the compounds were screened for their minimum inhibitory concentration (MIC) against the Gram-positive bacterium S. aureus, and interestingly, only the selenium analogues showed antibacterial activity, with 3c and 3e being the most potent with a MIC of 15.6 µM.


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