scholarly journals Hesperidin inhibits biofilm formation, virulence and staphyloxanthin synthesis in methicillin resistant Staphylococcus aureus by targeting SarA and CrtM: An in vitro and in silico approach

Author(s):  
Vijayakumar Karuppiah ◽  
Muhilvannan Seralathan ◽  
Arunvignesh Mani

Abstract Methicillin resistant Staphylococcus aureus is considered the multidrug resistant bacterium due to developing biofilm formation associated with antimicrobial resistance mechanisms. Therefore, inhibition of biofilm formation is an alternative therapeutic action to control MRSA infections. The present study revealed the non-antibacterial biofilm inhibitory potential of hesperidin against ATCC strain and clinical isolates of S. aureus. In addition, hesperidin treatment significantly impedes lipase, hemolysin, autolysin, autoaggregation and staphyloxanthin production. Reductions of staphyloxanthin production possibly increase the MRSA susceptibility rate to H2O2 oxidative stress condition. In gene expression study revealed the hesperidin treatment downregulated the biofilm-associated gene (sarA), polysaccharide intracellular adhesion gene (icaA and icaD), autolysin (altA), fibronectin-binding protein (fnbA and fnbB) and staphyloxanthin production (crtM). Molecular docking analysis predicted the ability of hesperidin to interact with SarA and CrtM proteins involved in biofilm formation and staphyloxanthin production in MRSA.

2010 ◽  
Vol 124 (6) ◽  
pp. 594-598 ◽  
Author(s):  
C H Jang ◽  
H Park ◽  
Y B Cho ◽  
C H Choi

AbstractBackground and objective:Bacterial biofilm formation has been implicated in the high incidence of persistent otorrhoea after tympanostomy tube insertion. It has been suggested that the tube material may be an important factor in the persistence of such otorrhoea. Development of methicillin-resistant Staphylococcus aureus otorrhoea after tympanostomy tube placement is a growing concern. We evaluated the effect of using vancomycin and chitosan coated tympanostomy tubes on the incidence of methicillin-resistant Staphylococcus aureus biofilm formation in vitro.Materials and methods:Three sets each of vancomycin-coated silicone tubes (n = 5), commercial silver oxide coated silicone tubes (n = 5) and uncoated tympanostomy tubes (as controls; n = 5) were compared as regards resistance to methicillin-resistant Staphylococcus aureus biofilm formation after in vitro incubation.Results:Scanning electron microscopy showed that the surfaces of the silver oxide coated tubes supported the formation of thick biofilms with crusts, comparable to the appearance of the uncoated tubes. In contrast, the surface of the vancomycin-coated tympanostomy tubes was virtually devoid of methicillin-resistant Staphylococcus aureus biofilm.Conclusion:Vancomycin-coated tympanostomy tubes resist methicillin-resistant Staphylococcus aureus biofilm formation. Pending further study, such tubes show promise in assisting the control of methicillin-resistant Staphylococcus aureus biofilm formation.


2016 ◽  
Vol 60 (10) ◽  
pp. 5688-5694 ◽  
Author(s):  
Daniel G. Meeker ◽  
Karen E. Beenken ◽  
Weston B. Mills ◽  
Allister J. Loughran ◽  
Horace J. Spencer ◽  
...  

ABSTRACTWe usedin vitroandin vivomodels of catheter-associated biofilm formation to compare the relative activity of antibiotics effective against methicillin-resistantStaphylococcus aureus(MRSA) in the specific context of an established biofilm. The results demonstrated that, underin vitroconditions, daptomycin and ceftaroline exhibited comparable activity relative to each other and greater activity than vancomycin, telavancin, oritavancin, dalbavancin, or tigecycline. This was true when assessed using established biofilms formed by the USA300 methicillin-resistant strain LAC and the USA200 methicillin-sensitive strain UAMS-1. Oxacillin exhibited greater activity against UAMS-1 than LAC, as would be expected, since LAC is an MRSA strain. However, the activity of oxacillin was less than that of daptomycin and ceftaroline even against UAMS-1. Among the lipoglycopeptides, telavancin exhibited the greatest overall activity. Specifically, telavancin exhibited greater activity than oritavancin or dalbavancin when tested against biofilms formed by LAC and was the only lipoglycopeptide capable of reducing the number of viable bacteria below the limit of detection. With biofilms formed by UAMS-1, telavancin and dalbavancin exhibited comparable activity relative to each other and greater activity than oritavancin. Importantly, ceftaroline was the only antibiotic that exhibited greater activity than vancomycin when testedin vivoin a murine model of catheter-associated biofilm formation. These results emphasize the need to consider antibiotics other than vancomycin, most notably, ceftaroline, for the treatment of biofilm-associatedS. aureusinfections, including by the matrix-based antibiotic delivery methods often employed for local antibiotic delivery in the treatment of these infections.


2021 ◽  
Vol 12 ◽  
Author(s):  
Agathe Boudet ◽  
Pauline Sorlin ◽  
Cassandra Pouget ◽  
Raphaël Chiron ◽  
Jean-Philippe Lavigne ◽  
...  

Cystic fibrosis (CF) is a genetic disease with lung abnormalities making patients particularly predisposed to pulmonary infections. Staphylococcus aureus is the most frequently identified pathogen, and multidrug-resistant strains (MRSA, methicillin-resistant S. aureus) have been associated with more severe lung dysfunction leading to eradication recommendations. Diverse bacterial traits and adaptive skills, including biofilm formation, may, however, make antimicrobial therapy challenging. In this context, we compared the ability of a collection of genotyped MRSA isolates from CF patients to form biofilm with and without antibiotics (ceftaroline, ceftobiprole, linezolid, trimethoprim, and rifampicin). Our study used standardized approaches not previously applied to CF MRSA, the BioFilm Ring test® (BRT®), the Antibiofilmogram®, and the BioFlux™ 200 system which were adapted for use with the artificial sputum medium (ASM) mimicking conditions more relevant to the CF lung. We included 63 strains of 10 multilocus sequence types (STs) isolated from 35 CF patients, 16 of whom had chronic colonization. The BRT® showed that 27% of the strains isolated in 37% of the patients were strong biofilm producers. The Antibiofilmogram® performed on these strains showed that broad-spectrum cephalosporins had the lowest minimum biofilm inhibitory concentrations (bMIC) on a majority of strains. A focus on four chronically colonized patients with inclusion of successively isolated strains showed that ceftaroline, ceftobiprole, and/or linezolid bMICs may remain below the resistance thresholds over time. Studying the dynamics of biofilm formation by strains isolated 3years apart in one of these patients using BioFlux™ 200 showed that inhibition of biofilm formation was observed for up to 36h of exposure to bMIC and ceftaroline and ceftobiprole had a significantly greater effect than linezolid. This study has brought new insights into the behavior of CF MRSA which has been little studied for its ability to form biofilm. Biofilm formation is a common characteristic of prevalent MRSA clones in CF. Early biofilm formation was strain-dependent, even within a sample, and not only observed during chronic colonization. Ceftaroline and ceftobiprole showed a remarkable activity with a long-lasting inhibitory effect on biofilm formation and a conserved activity on certain strains adapted to the CF lung environment after years of colonization.


2013 ◽  
Vol 12 (4) ◽  
pp. 427-431
Author(s):  
S Ahmad

Background: Methicillin resistant Staphylococcus aureus (MRSA) is a multidrug resistant organism that threatens the effectiveness of antibiotics worldwide and is a threat in hospitals and long-term care settings. Aims: To determine the proportion of MRSA strains and their in vitro antibiotic susceptibility patterns against various antibiotics. Material and Methods: Different clinical specimens (n= 679) received at Al-Haram Diagnostic, Research and Training Center, Kashmir during a two year period commencing January, 2009 to December, 2010 were cultured, the isolates identified using standard microbiological techniques and their antibiotic susceptibilities determined. Results: Of the 679 specimens, Staphylococcus. aureus was isolated in 127 and 32 (25.2%) of these 127 were found be MRSA. No significant association with age or sex were observed in the MRSA positive specimens. MRSA were mainly isolated from burns, and skin and superficial soft tissue infections. MRSA isolates were found to be 100% sensitive to Vancomycin and 94%, 87%, 81%, 78% and 75% of isolates were resistant to Gentamycin, Tetracycline, Clindamycin, Erythromycin and Co-trimoxazole respectively. Conclusions: The relatively high proportion of MRSA and the associated antibiotic resistance seen in this study emphasizes the need for local or country based surveillance to characterize and monitor MRSA and to develop strategies that will improve MRSA treatment and control. DOI: http://dx.doi.org/10.3329/bjms.v12i4.16663 Bangladesh Journal of Medical Science Vol. 12 No. 04 October ’13 Page 427-431


2021 ◽  
Vol 28 (4) ◽  
pp. 24-36
Author(s):  
Mohd Taufiq Mat Jalil ◽  
Darah Ibrahim

Background: The emergence of multidrug-resistant pathogens associated with biofilm formation can cause life-threatening infections to humans. Therefore, the present study aims to evaluate the effects of the fungal extract of Lasiodiplodia pseudotheobromae (L. pseudotheobromae) Industrial Biotechnology Research Laboratory (IBRL) OS-64 on bacterial cells and the biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA). Methods: Broth microdilution and semi-quantitative adherence assays were conducted to determine the anti-biofilm activity of the fungal extract. Light and scanning electron microscopy (SEM) analyses were performed to observe the effect of the fungal extract on biofilm formation by MRSA. Results: The transmission electron microscopy (TEM) microphotographs showed that the bacterial cells were severely damaged upon 24 h exposure to the extract and displayed several symptoms such as cell shrinkage and breakage. Meanwhile, results from the antibiofilm study indicated the extract attenuated the initial and preformed biofilms of MRSA by 80.82% and 61.39%, respectively. The initial biofilm was more sensitive to the extract compared to the pre-formed biofilm, as evidenced by the light microscopy and SEM observations that demonstrated more severe bacterial cell damage on the initial biofilms compared to pre-formed biofilms. Conclusion: The ethyl acetate extract of L. pseudotheobromae IBRL OS-64 significantly inhibited bacterial cells growth and eliminated biofilm formation by MRSA.


ACS Omega ◽  
2020 ◽  
Vol 5 (48) ◽  
pp. 31100-31114
Author(s):  
Anthonymuthu Selvaraj ◽  
Alaguvel Valliammai ◽  
Pandiyan Muthuramalingam ◽  
Arumugam Priya ◽  
Manokaran Suba ◽  
...  

2011 ◽  
Vol 55 (5) ◽  
pp. 2042-2053 ◽  
Author(s):  
Roya Zoraghi ◽  
Raymond H. See ◽  
Peter Axerio-Cilies ◽  
Nag S. Kumar ◽  
Huansheng Gong ◽  
...  

ABSTRACTNovel classes of antimicrobials are needed to address the challenge of multidrug-resistant bacteria such as methicillin-resistantStaphylococcus aureus(MRSA). Using the architecture of the MRSA interactome, we identified pyruvate kinase (PK) as a potential novel drug target based upon it being a highly connected, essential hub in the MRSA interactome. Structural modeling, including X-ray crystallography, revealed discrete features of PK in MRSA, which appeared suitable for the selective targeting of the bacterial enzyme.In silicolibrary screening combined with functional enzymatic assays identified an acyl hydrazone-based compound (IS-130) as a potent MRSA PK inhibitor (50% inhibitory concentration [IC50] of 0.1 μM) with >1,000-fold selectivity over human PK isoforms. Medicinal chemistry around the IS-130 scaffold identified analogs that more potently and selectively inhibited MRSA PK enzymatic activity andS. aureusgrowthin vitro(MIC of 1 to 5 μg/ml). These novel anti-PK compounds were found to possess antistaphylococcal activity, including both MRSA and multidrug-resistantS. aureus(MDRSA) strains. These compounds also exhibited exceptional antibacterial activities against other Gram-positive genera, including enterococci and streptococci. PK lead compounds were found to be noncompetitive inhibitors and were bactericidal. In addition, mutants with significant increases in MICs were not isolated after 25 bacterial passages in culture, indicating that resistance may be slow to emerge. These findings validate the principles of network science as a powerful approach to identify novel antibacterial drug targets. They also provide a proof of principle, based upon PK in MRSA, for a research platform aimed at discovering and optimizing selective inhibitors of novel bacterial targets where human orthologs exist, as leads for anti-infective drug development.


Author(s):  
Hye-Kyung Cho ◽  
Melissa J. Karau ◽  
Kerryl E. Greenwood-Quaintance ◽  
Karl A. Hansford ◽  
Matthew A. Cooper ◽  
...  

MRSA periprosthetic 1 joint infection (PJI) can be challenging to treat due to biofilm formation, alongside sometimes limited vancomycin activity (1-3).…


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