Antibiofilm Effect of Adamantane Derivative against Staphylococcus aureus

2021 ◽  
Vol 83 (1) ◽  
pp. 58-67
Author(s):  
N.I. Hrynchuk ◽  
◽  
N.O. Vrynchanu ◽  
T.A. Buchtyarova ◽  
D.M. Dudikova ◽  
...  

Currently, one of the most urgent problems in clinical practice is the antibiotic therapy ineffectiveness at chronic diseases treatment caused by biofilms-forming microorganisms. One of the ways to its solution is the search for new compounds with antibiofilm activity which can prevent the adhesion of microorganisms, disrupt the structure of the biofilm matrix and affect the Quorum sensing system. The aim of the study was to investigate adamantane derivative 1-[4-(1-adamantyl) phenoxy]-3-(N-benzyl,N-dimethylamino)-2-propanol chloride (KVM-97) antimicrobial activity mechanism against Staphylococcus aureus biofilms. Methods. The ability of the adamantane derivative KVM-97 to prevent S. aureus biofilm formation and to destroy previously formed biofilms has been tested on polystyrene plates by gentian violet sorption on these structures, followed by desorption with organic solvent and use of resazurin (redox indicator). The S. aureus cells viability in mature biofilms was evaluated with specific dyes for living (acridine orange) and dead (propidium iodide) cells. Lowry method was used to assess the effect of KVM-97 on the matrix components for the total protein contents determination, the polysaccharides were detected spectrophotometrically (using phenol and sulfuric acid), Bap-protein – by test with Congo red. Persisters’ subpopulation was detected by activation of the SOS response in bacteria when exposed to high concentrations of antimicrobial substances. Results. It was found that KVM-97 (the compound with the adamantyl radical) showed an antibiofilm effect against S. aureus, decreasing biofilm biomass: at the biofilm formation stage – by 22.5% and 75.0%, while in case of 2-day biofilms treatment – by 34.5% and 32.4% at 0.5 MIC and 5.0 MIC respectively. Compound KVM-97 was able to reduce the number of metabolically active S. aureus cells only at the stage of biofilm formation (reduction by 92.7 and 95.8% at 2.0 and 5.0 MIC). Obtained results indicated that this adamantane-containing compound did not affect the protein and polysaccharides contents of S. aureus biofilms matrix. The changes of Bap-protein level caused by KVM-97 were not statistically significant (p>0.05). It was shown that KVM-97 did not prevent the formation of metabolically inactive persister cells; their share was 0.71% of the control. Conclusions. Thus, adamantane-containing compound KVM-97 is able to prevent S. aureus biofilm formation, causing significant biofilms’ mass reduction, as well as lowering the viable cells number in them and destroying already formed biofilms. Its antibiofilm effects are not associated with matrix protein and polysaccharides synthesis impairments. Further thorough investigations are needed to establish the effect of this compound on eDNA synthesis, the Quorum sensing system, and the ica and arg genes expression of S. aureus responsible for biofilm formation.

2020 ◽  
Vol 8 (8) ◽  
pp. 1131 ◽  
Author(s):  
Mihael Špacapan ◽  
Tjaša Danevčič ◽  
Polonca Štefanic ◽  
Michael Porter ◽  
Nicola R. Stanley-Wall ◽  
...  

Quorum sensing (QS) is often required for the formation of bacterial biofilms and is a popular target of biofilm control strategies. Previous studies implicate the ComQXPA quorum sensing system of Bacillus subtilis as a promoter of biofilm formation. Here, we report that ComX signaling peptide deficient mutants form thicker and more robust pellicle biofilms that contain chains of cells. We confirm that ComX positively affects the transcriptional activity of the PepsA promoter, which controls the synthesis of the major matrix polysaccharide. In contrast, ComX negatively controls the PtapA promoter, which drives the production of TasA, a fibrous matrix protein. Overall, the biomass of the mutant biofilm lacking ComX accumulates more monosaccharide and protein content than the wild type. We conclude that this QS phenotype might be due to extended investment into growth rather than spore development. Consistent with this, the ComX deficient mutant shows a delayed activation of the pre-spore specific promoter, PspoIIQ, and a delayed, more synchronous commitment to sporulation. We conclude that ComX mediated early commitment to sporulation of the wild type slows down biofilm formation and modulates the coexistence of multiple biological states during the early stages of biofilm development.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cristian Dotto ◽  
Andrea Lombarte Serrat ◽  
Martín Ledesma ◽  
Carlos Vay ◽  
Monika Ehling-Schulz ◽  
...  

AbstractSalicylic acid (SAL) has recently been shown to induce biofilm formation in Staphylococcus aureus and to affect the expression of virulence factors. This study was aimed to investigate the effect of SAL on the regulatory agr system and its impact on S. aureus biofilm formation. The agr quorum-sensing system, which is a central regulator in S. aureus pathogenicity, plays a pivotal role in the dispersal of S. aureus mature biofilms and contributes to the creation of new colonization sites. Here, we demonstrate that SAL impairs biofilm dispersal by interfering with agr expression. As revealed by our work, protease and surfactant molecule production is diminished, and bacterial cell autolysis is also negatively affected by SAL. Furthermore, as a consequence of SAL treatment, the S. aureus biofilm matrix revealed the lack of extracellular DNA. In silico docking and simulation of molecular dynamics provided evidence for a potential interaction of AgrA and SAL, resulting in reduced activity of the agr system. In conclusion, SAL stabilized the mature S. aureus biofilms, which may prevent bacterial cell dissemination. However, it may foster the establishment of infections locally and consequently increase bacterial persistence leading to therapeutic failure.


PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153468 ◽  
Author(s):  
Yan Chen ◽  
Tangjuan Liu ◽  
Ke Wang ◽  
Changchun Hou ◽  
Shuangqi Cai ◽  
...  

2019 ◽  
Vol 9 ◽  
Author(s):  
Ying Su ◽  
Kaihao Tang ◽  
Jiwen Liu ◽  
Yan Wang ◽  
Yanfen Zheng ◽  
...  

2019 ◽  
Author(s):  
Andrew A. Bridges ◽  
Bonnie L. Bassler

AbstractVibrio cholerae possesses multiple quorum-sensing systems that control virulence and biofilm formation among other traits. At low cell densities, when quorum-sensing autoinducers are absent, V. cholerae forms biofilms. At high cell densities, when autoinducers have accumulated, biofilm formation is repressed and dispersal occurs. Here, we focus on the roles of two well-characterized quorum-sensing autoinducers that function in parallel. One autoinducer, called CAI-1, is used to measure vibrio abundance, and the other autoinducer, called AI-2, is a broadly-made universal autoinducer that is presumed to enable V. cholerae to assess the total bacterial cell density of the vicinal community. The two V. cholerae autoinducers funnel information into a shared signal relay pathway. This feature of the quorum-sensing system architecture has made it difficult to understand how specific information can be extracted from each autoinducer, how the autoinducers might drive distinct output behaviors, and in turn, how the bacteria use quorum sensing to distinguish self from other in bacterial communities. We develop a live-cell biofilm formation and dispersal assay that allows examination of the individual and combined roles of the two autoinducers in controlling V. cholerae behavior. We show that the quorum-sensing system works as a coincidence detector in which both autoinducers must be present simultaneously for repression of biofilm formation to occur. Within that context, the CAI-1 quorum-sensing pathway is activated when only a few V. cholerae cells are present, whereas the AI-2 pathway is activated only at much higher cell density. The consequence of this asymmetry is that exogenous sources of AI-2, but not CAI-1, contribute to satisfying the coincidence detector to repress biofilm formation and promote dispersal. We propose that V. cholerae uses CAI-1 to verify that some of its kin are present before committing to the high-cell-density quorum-sensing mode, but it is, in fact, the universal autoinducer AI-2, that sets the pace of the V. cholerae quorum-sensing program. This first report of unique roles for the different V. cholerae autoinducers suggests that detection of self fosters a distinct outcome from detection of other.


mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Morgan L. Grundstad ◽  
Corey P. Parlet ◽  
Jakub M. Kwiecinski ◽  
Jeffrey S. Kavanaugh ◽  
Heidi A. Crosby ◽  
...  

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) infections impact all patient populations both in the community and in health care settings. Despite advances in our knowledge of MRSA virulence, little is known about the regulatory mechanisms of USA100 health care-associated MRSA isolates, which are the second most frequently identified MRSA isolates found in all infections. This work focused on the contribution of the USA100 agr type II quorum-sensing system to virulence and antibiotic resistance. From a MRSA strain collection, we selected 16 representative USA100 isolates, constructed mutants with Δagr mutations, and characterized selected strain pairs for virulence factor expression, murine skin infection, and antibiotic resistance. For each strain pair, hemolysis and extracellular protease expression were significantly greater in the wild-type (WT) strains than in the Δagr mutants. Similarly, mice challenged with the WT strains had larger areas of dermonecrosis and greater weight loss than those challenged with the Δagr mutants, demonstrating that the USA100 agr system regulates virulence. Although USA100 isolates exhibit a high level of antibiotic resistance, the WT and Δagr strain pairs showed no difference in MICs by MIC testing. However, in the presence of a sub-MIC of vancomycin, most of the USA100 Δagr mutants exhibited slower growth than the WT isolates, and a couple of the Δagr mutants also grew more slowly in the presence of a sub-MIC of cefoxitin. Altogether, our findings demonstrate that the USA100 agr system is a critical regulator of virulence, and it may have a contribution to the optimal survival of these MRSA strains in the presence of antibiotics. IMPORTANCE USA100 health care-associated MRSA isolates are highly antibiotic resistant and can cause invasive disease across all patient populations. Even though USA100 strains are some of the most frequently identified causes of infections, little is known about virulence regulation in these isolates. Our study demonstrates that the USA100 agr quorum-sensing system is important for the control of toxin and exoenzyme production and that the agr system has a key role in skin infection. In some USA100 isolates, the agr system is important for growth in the presence of low levels of antibiotics. Altogether, our findings demonstrate that the USA100 agr system is a critical regulator of virulence and that it may make a contribution to the optimal survival of these MRSA strains in the presence of antibiotics.


2011 ◽  
Vol 79 (10) ◽  
pp. 4050-4060 ◽  
Author(s):  
Jorge E. Vidal ◽  
Herbert P. Ludewick ◽  
Rebekah M. Kunkel ◽  
Dorothea Zähner ◽  
Keith P. Klugman

ABSTRACTStreptococcus pneumoniaeis the leading cause of death in children worldwide and forms highly organized biofilms in the nasopharynx, lungs, and middle ear mucosa. TheluxS-controlled quorum-sensing (QS) system has recently been implicated in virulence and persistence in the nasopharynx, but its role in biofilms has not been studied. Here we show that this QS system plays a major role in the control ofS. pneumoniaebiofilm formation. Our results demonstrate that theluxSgene is contained by invasive isolates and normal-flora strains in a region that contains genes involved in division and cell wall biosynthesis. TheluxSgene was maximally transcribed, as a monocistronic message, in the early mid-log phase of growth, and this coincides with the appearance of early biofilms. Demonstrating the role of the LuxS system in regulatingS. pneumoniaebiofilms, at 24 h postinoculation, two different D39ΔluxSmutants produced ∼80% less biofilm biomass than wild-type (WT) strain D39 did. Complementation of these strains withluxS, either in a plasmid or integrated as a single copy in the genome, restored their biofilm level to that of the WT. Moreover, a soluble factor secreted by WT strain D39 or purified AI-2 restored the biofilm phenotype of D39ΔluxS. Our results also demonstrate that during the early mid-log phase of growth, LuxS regulates the transcript levels oflytA, which encodes an autolysin previously implicated in biofilms, and also the transcript levels ofply, which encodes the pneumococcal pneumolysin. In conclusion, theluxS-controlled QS system is a key regulator of early biofilm formation byS. pneumoniaestrain D39.


2016 ◽  
Vol 7 ◽  
Author(s):  
Jaime Canovas ◽  
Mara Baldry ◽  
Martin S. Bojer ◽  
Paal S. Andersen ◽  
Bengt H. Gless ◽  
...  

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