scholarly journals Conjugation of LasR Quorum-Sensing Inhibitors with Ciprofloxacin Decreases the Antibiotic Tolerance ofP. aeruginosaClinical Strains

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Daria Bortolotti ◽  
Claudio Trapella ◽  
Alessandra Bragonzi ◽  
Paolo Marchetti ◽  
Vinicio Zanirato ◽  
...  

Pseudomonas aeruginosais a Gram-negative bacterium that commonly infects subjects with weakened immune system causing deadly infections above all at pulmonary level. During infection,P. aeruginosaproduces a well-organized bacterial structure, called biofilm, activating the quorum-sensing (QS) signaling, a mechanism of gene regulation. In this work, we synthesized already known QS inhibitors (QSi) designed on the scaffold of the N-(3-oxododecanoyl) homoserine lactone (3O-C12-HSL) QS molecule and conjugated them with ciprofloxacin to inhibitP. aeruginosabiofilm formation and increase the antibiotic susceptibility of clinical strains. We identified, for the first time, a QSi conjugated with ciprofloxacin (ET37), that is able to reduce the formation of biofilm and the onset of tolerant clones inP. aeruginosaclinical strains. This compound could have a wide application in clinical setting. The possibility to affect biofilm formation in chronically infected patients, such as patients affected by cystic fibrosis, and to reduce the onset of ciprofloxacin resistance would improve patient healing and allow to decrease antibiotic drug dosage.


2019 ◽  
Vol 22 (1) ◽  
Author(s):  
Tepoerau Mai ◽  
Jordan Toullec ◽  
Simon Van Wynsberge ◽  
Marc Besson ◽  
Stephanie Soulet ◽  
...  

AbstractMarine natural products isolated from the sponge Fascaplysinopsis cf reticulata, in French Polynesia, were investigated as an alternative to antibiotics to control pathogens in aquaculture. The overuse of antibiotics in aquaculture is largely considered to be an environmental pollution, because it supports the transfer of antibiotic resistance genes within the aquatic environment. One environmentally friendly alternative to antibiotics is the use of quorum sensing inhibitors (QSIs). Quorum sensing (QS) is a regulatory mechanism in bacteria which control virulence factors through the secretion of autoinducers (AIs), such as acyl-homoserine lactone (AHL) in gram-negative bacteria. Vibrio harveyi QS is controlled through three parallel pathways: HAI-1, AI-2, and CAI-1. Bioassay-guided purification of F. cf reticulata extract was conducted on two bacterial species, i.e., Tenacibaculum maritimum and V. harveyi for antibiotic and QS inhibition bioactivities. Toxicity bioassay of fractions was also evaluated on the freshwater fish Poecilia reticulata and the marine fish Acanthurus triostegus. Cyclohexanic and dichloromethane fractions of F. cf reticulata exhibited QS inhibition on V. harveyi and antibiotic bioactivities on V. harveyi and T. maritimum, respectively. Palauolide (1) and fascaplysin (2) were purified as major molecules from the cyclohexanic and dichloromethane fractions, respectively. Palauolide inhibited QS of V. harveyi through HAI-1 QS pathway at 50 μg ml–1 (26 μM), while fascaplysin affected the bacterial growth of V. harveyi (50 μg ml–1) and T. maritimum (0.25 μg). The toxicity of fascaplysin-enriched fraction (FEF) was evaluated and exhibited a toxic effect against fish at 50 μg ml–1. This study demonstrated for the first time the QSI potential of palauolide (1). Future research may assess the toxicity of both the cyclohexanic fraction of the sponge and palauolide (1) on fish, to confirm their potential as alternative to antibiotics in fish farming.



2020 ◽  
Vol 26 ◽  
Author(s):  
Madison Tonkin ◽  
Shama Khan ◽  
Mohmmad Younus Wani ◽  
Aijaz Ahmad

: Quorum sensing is defined as cell to cell communication between microorganisms, which enables microorganisms to behave as multicellular organisms. Quorum sensing enables many collaborative benefits such as synchronisation of virulence factors and biofilm formation. Both quorum sensing as well as biofilm formation encourage the development of drug resistance in microorganisms. Biofilm formation and quorum sensing are causally linked to each other and play role in the pathogenesis of microorganisms. With the increasing drug resistance against the available antibiotics and antifungal medications, scientists are combining different options to develop new strategies. Such strategies rely on the inhibition of the communication and virulence factors rather than on killing or inhibiting the growth of the microorganisms. This review encompasses the communication technique used by microorganisms, how microorganism resistance is linked to quorum sensing and various chemical strategies to combat quorum sensing and thereby drug resistance. Several compounds have been identified as quorum sensing inhibitors and are known to be effective in reducing resistance as they do not kill the pathogens but rather disrupt their communication. Natural compounds have been identified as anti-quorum sensing agents. However, natural compounds present several related disadvantages. Therefore, the need for the development of synthetic or semi-synthetic compounds has arisen. This review argues that anti-quorum sensing compounds are effective in disrupting quorum sensing and could therefore be effective in reducing microorganism drug resistance.



2013 ◽  
Vol 825 ◽  
pp. 107-110
Author(s):  
Sören Bellenberg ◽  
Robert Barthen ◽  
Mario Vera ◽  
Nicolas Guiliani ◽  
Wolfgang Sand

A functional luxIR-type Quorum Sensing (QS) system is present in Acidithiobacillus ferrooxidans. However, cell-cell communication among various acidophilic chemolithoautotrophs growing on pyrite has not been studied in detail. These aspects are the scope of this study with emphasis on the effects exerted by the N-acyl-homoserine lactone (AHL) type signaling molecules which are produced by Acidithiobacillus ferrooxidans. Their effects on attachment and leaching efficiency by other leaching bacteria, such as Acidithiobacillus ferrivorans, Acidiferrobacter spp. SPIII/3 and Leptospirillum ferrooxidans in pure and mixed cultures growing on pyrite is shown.



2013 ◽  
Vol 76 (2) ◽  
pp. 239-247 ◽  
Author(s):  
IQBAL KABIR JAHID ◽  
NA-YOUNG LEE ◽  
ANNA KIM ◽  
SANG-DO HA

Aeromonas hydrophila recently has received increased attention because it is opportunistic and a primary human pathogen. A. hydrophila biofilm formation and its control are a major concern for food safety because biofilms are related to virulence. Therefore, we investigated biofilm formation, motility inhibition, quorum sensing, and exoprotease production of this opportunistic pathogen in response to various glucose concentrations from 0.05 to 2.5% (wt/vol). More than 0.05% glucose significantly impaired (P < 0.05) quorum sensing, biofilm formation, protease production, and swarming and swimming motility, whereas bacteria treated with 0.05% glucose had activity similar to that of the control (0% glucose). A stage shift biofilm assay revealed that the addition of glucose (2.5%) inhibited initial biofilm formation but not later stages. However, addition of quorum sensing molecules N-3-butanoyl-DL-homoserine lactone and N-3-hexanoyl homoserine lactone partially restored protease production, indicating that quorum sensing is controlled by glucose concentrations. Thus, glucose present in food or added as a preservative could regulate acyl-homoserine lactone quorum sensing molecules, which mediate biofilm formation and virulence in A. hydrophila.



2007 ◽  
Vol 73 (20) ◽  
pp. 6339-6344 ◽  
Author(s):  
Tomohiro Morohoshi ◽  
Toshitaka Shiono ◽  
Kiyomi Takidouchi ◽  
Masashi Kato ◽  
Norihiro Kato ◽  
...  

ABSTRACT Quorum sensing is a regulatory system for controlling gene expression in response to increasing cell density. N-Acylhomoserine lactone (AHL) is produced by gram-negative bacteria, which use it as a quorum-sensing signal molecule. Serratia marcescens is a gram-negative opportunistic pathogen which is responsible for an increasing number of serious nosocomial infections. S. marcescens AS-1 produces N-hexanoyl homoserine lactone (C6-HSL) and N-(3-oxohexanoyl) homoserine lactone and regulates prodigiosin production, swarming motility, and biofilm formation by AHL-mediated quorum sensing. We synthesized a series of N-acyl cyclopentylamides with acyl chain lengths ranging from 4 to 12 and estimated their inhibitory effects on prodigiosin production in AS-1. One of these molecules, N-nonanoyl-cyclopentylamide (C9-CPA), had a strong inhibitory effect on prodigiosin production. C9-CPA also inhibited the swarming motility and biofilm formation of AS-1. A competition assay revealed that C9-CPA was able to inhibit quorum sensing at four times the concentration of exogenous C6-HSL and was more effective than the previously reported halogenated furanone. Our results demonstrated that C9-CPA was an effective quorum-sensing inhibitor for S. marcescens AS-1.



2001 ◽  
Vol 67 (4) ◽  
pp. 1865-1873 ◽  
Author(s):  
Teresa R. De Kievit ◽  
Richard Gillis ◽  
Steve Marx ◽  
Chris Brown ◽  
Barbara H. Iglewski

ABSTRACT Acylated homoserine lactone molecules are used by a number of gram-negative bacteria to regulate cell density-dependent gene expression by a mechanism known as quorum sensing (QS). InPseudomonas aeruginosa, QS or cell-to-cell signaling controls expression of a number of virulence factors, as well as biofilm differentiation. In this study, we investigated the role played by the las and rhl QS systems during the early stages of static biofilm formation when cells are adhering to a surface and forming microcolonies. These studies revealed a marked difference in biofilm formation between the PAO1 parent and the QS mutants when glucose, but not citrate, was used as the sole carbon source. To further elucidate the contribution of lasI andrhlI to biofilm maturation, we utilized fusions to unstable green fluorescent protein in concert with confocal microscopy to perform real-time temporal and spatial studies of these genes in a flowing environment. During the course of 8-day biofilm development,lasI expression was found to progressively decrease over time. Conversely, rhlI expression remained steady throughout biofilm development but occurred in a lower percentage of cells. Spatial analysis revealed that lasI andrhlI were maximally expressed in cells located at the substratum and that expression decreased with increasing biofilm height. Because QS was shown previously to be involved in biofilm differentiation, these findings have important implications for the design of biofilm prevention and eradication strategies.





Biofilms ◽  
2004 ◽  
Vol 1 (2) ◽  
pp. 91-99 ◽  
Author(s):  
S. R. Schooling ◽  
U. K. Charaf ◽  
D. G. Allison ◽  
P. Gilbert

Biofilms are often considered as localized zones of high cell density. Quorum sensing provides a means for control of population processes and has been implicated in the regulation of biofilm activities. We present a role for quorum sensing in programmed detachment and dispersal processes. Biofilms of Pseudomonas aeruginosa PAO1 and its isogenic homoserine lactone (HSL) mutant P. aeruginosa PAO-JP2 were grown in batch culture on glass substrata; differences were found in the rate and extent of formation of biofilm. Climax communities were observed for PAO1 at 24 h. These were later accompanied by foaming, a drop in the surface tension of culture media and dispersal of the biofilm, after which no subsequent biofilm accretion occurred. PAO-JP2 cultures reformed biofilm post-detachment and did not foam. Prevention of biofilm reformation in the wild type was related to some component excreted into the culture medium. Rhamnolipid, a biosurfactant regulated by quorum sensing, was detected in PAO1 cultures. When rhamnolipid was added to freshly inoculated substrata, biofilm formation was inhibited. At 20 h, PAO1 biofilms were transferred to medium with added rhamnolipid: biofilm was relatively unaffected. Biofilm events were also studied in medium supplemented with N-butyryl-L-homoserine lactone, which is involved in the regulation of rhamnolipid synthesis. Both strains exhibited similar trends of rapid biofilm formation and dramatic changes in the rate and extent of biofilm accretion. In both cases, there was premature foaming, lowered surface tension and elevated rhamnolipid levels. A role for HSLs in maintenance of biofilm and events leading to dispersion of cells is proposed. This role would encompass dispersion but not necessarily detachment of cells from biofilm and supports a new function for rhamnolipid in pathogenesis, whereby rhamnolipid would promote the dissemination of cells from a nidus of infection.



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