scholarly journals Treatment of Staphylococcus aureus Biofilm Infection by the Quorum-Sensing Inhibitor RIP

2007 ◽  
Vol 51 (6) ◽  
pp. 2226-2229 ◽  
Author(s):  
Naomi Balaban ◽  
Oscar Cirioni ◽  
Andrea Giacometti ◽  
Roberto Ghiselli ◽  
Joel B. Braunstein ◽  
...  

ABSTRACT The quorum-sensing inhibitor RIP inhibits staphylococcal TRAP/agr systems and both TRAP- and agr-negative strains are deficient in biofilm formation in vivo, indicating the importance of quorum sensing to biofilms in the host. RIP injected systemically into rats has been found to have strong activity in preventing methicillin-resistant Staphylococcus aureus graft infections, suggesting that RIP can be used as a therapeutic agent.

2006 ◽  
Vol 51 (7) ◽  
pp. 2594-2596 ◽  
Author(s):  
Paloma Anguita-Alonso ◽  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Fiorenza Orlando ◽  
...  

ABSTRACT Staphylococci, common orthopedic pathogens, form antibiotic-resistant biofilms. Polymethylmethacrylate (PMMA) beads loaded with the quorum-sensing inhibitor RNAIII-inhibiting peptide (RIP) were implanted in rats and shown to prevent methicillin-resistant Staphylococcus aureus infection. RIP release was bimodal, typical of previously-tested antibiotics. These results suggest that RIP-PMMA warrants further evaluation for management of orthopedic infections caused by staphylococci.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Shizhou Wu ◽  
Yunjie Liu ◽  
Hui Zhang ◽  
Lei Lei

Aim. Antibiotic abuse contributes to the emergence of methicillin-resistant Staphylococcus aureus (MRSA). It is increasingly important to screen new antimicrobial agents for the management of MRSA infections. G. chinensis, a nontoxic Chinese herbal medicine, is considered a potential antibacterial agent. The aim of this study was to investigate the bactericidal effects of the aqueous extracts of G. chinensis on MRSA. The potential mechanisms of G. chinensis aqueous extract inhibition of the pathogenicity of MRSA in vivo are also discussed. Methods. G. chinensis aqueous extract was prepared and its antimicrobial activities were examined by determining its minimum inhibitory concentration (MIC). Biofilm biomass was determined by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). RNA sequencing (RNA-seq) was used to evaluate differentially expressed functional pathways in MRSA treated with G. chinensis aqueous extract. We validated the role of G. chinensis aqueous extract in the invasive ability and pathogenicity of MRSA in vivo using a rat infectious model. Results. The results indicated that MRSA was sensitive to the G. chinensis aqueous extracts at concentration of 31.25μg/mL. G. chinensis extract led to a reduction in dextran-dependent aggregation and biofilm formation in MRSA. Based on the transcriptome analysis, G. chinensis aqueous extracts significantly downregulated the gene expression related to biofilm formation and carbohydrate metabolism. G. chinensis aqueous extract inhibited the invasive ability and the pathogenicity of MRSA in vivo. Conclusion. The antimicrobial properties of G. chinensis aqueous extract are likely related to its modulation of MRSA biofilm formation and carbohydrate metabolism. G. chinensis aqueous extract is a promising supplementary therapy to lessen or eliminate the use of antibiotics and is a potential tool for the management of MRSA infections.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Shizhou Wu ◽  
Yunjie Liu ◽  
Lei Lei ◽  
Hui Zhang

Abstract Objectives Methicillin-resistant Staphylococcus aureus (MRSA) strains present an urgent medical problem in osteomyelitis cases. Our previous study indicated that the YycFG two-component regulatory pathway is associated with the bacterial biofilm organization of MRSA strains. The aim of this study was to investigate the regulatory roles of ASyycG in the bacterial biofilm formation and the pathogenicity of MRSA strains using an antisense RNA strategy. Methods An ASyycG-overexpressing MRSA clinical isolate was constructed. The bacterial growth was monitored, and the biofilm biomass on bone specimens was examined using scanning electron microscopy and confocal laser scanning microscopy. Furthermore, quantitative RT-PCR (QRT-PCR) analysis was used to measure the expression of yycF/G/H and icaA/D in the MRSA and ASyycG strains. The expression of the YycG protein was quantified by Western blot assays. We validated the role of ASyycG in the invasive ability and pathogenicity of the strains in vivo using histology and peptide nucleic acid fluorescent in situ hybridization. Results The results showed that overexpression of ASyycG lead to a reduction in biofilm formation and exopolysaccharide (EPS) synthesis compared to the control MRSA strains. The ASyycG strains exhibited decreased expression of the yycF/G/H and icaA/D genes. Furthermore, Western blot data showed that the production of the YycG protein was inhibited in the ASyycG strains. In addition, we demonstrated that ASyycG suppressed the invasive ability and pathogenicity of the strain in vivo using an SPF (specific pathogen free) rat model. Conclusion In summary, the overexpression of ASyycG leads to a reduction in biofilm formation and bacterial pathogenicity in vivo, which provides a potential target for the management of MRSA-induced osteomyelitis.


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.


2003 ◽  
Vol 187 (4) ◽  
pp. 625-630 ◽  
Author(s):  
Naomi Balaban ◽  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Yael Gov ◽  
Roberto Ghiselli ◽  
...  

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.


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

2007 ◽  
Vol 51 (12) ◽  
pp. 4518-4520 ◽  
Author(s):  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Daniele Minardi ◽  
Fiorenza Orlando ◽  
Federico Mocchegiani ◽  
...  

ABSTRACT Ureteral stents coated with the quorum-sensing inhibitor RNAIII-inhibiting peptide (RIP) were implanted in rat bladders and shown to suppress Staphylococcus aureus formation on the stent and in urine and was especially effective when combined with teicoplanin. Coating ureteral stents with RIP thus increases the efficacy of teicoplanin in preventing ureteral stent-associated staphylococcal infections.


1996 ◽  
Vol 40 (11) ◽  
pp. 2529-2534 ◽  
Author(s):  
M B Frosco ◽  
J L Melton ◽  
F P Stewart ◽  
B A Kulwich ◽  
L Licata ◽  
...  

Levofloxacin, the active L-isomer of ofloxacin, has demonstrated strong activity against Staphylococcus aureus both in vitro and in vivo. In a murine model of hematogenous pyelonephritis, the in vivo efficacies of levofloxacin and ciprofloxacin were evaluated against two methicillin-susceptible and two methicillin-resistant S. aureus strains. All four isolates had virtually identical susceptibilities to levofloxacin and ciprofloxacin. Pyelonephritis was induced in carrageenan-primed mice by an intravenous injection of 0.5 ml of 10(7) CFU of methicillin-susceptible S. aureus isolates per ml or 10(8) CFU of methicillin-resistant S. aureus isolates per ml. At 1 h postinfection, the mice were treated orally with levofloxacin or ciprofloxacin once a day or twice a day (total daily dose of 20 to 160 mg/kg of body weight) for 4 days. Mice were euthanized 24 h after the final treatment, and the kidneys were excised and weighed. The kidneys were prepared for histological examination or were homogenized to determine the numbers of CFU per gram of tissue quantitatively. The reduction in the mean log10 number of CFU per gram as a function of total daily dose was recorded. A dose-response analysis showed that levofloxacin was superior to ciprofloxacin for all four isolates at any dose or regimen tested, independent of the methicillin susceptibility of the isolates. By using an inverse prediction technique, the equivalent effective doses of levofloxacin (once a day) were less than those of ciprofloxacin (twice a day) by 5.2 and 3.2 times, respectively, for methicillin-susceptible S. aureus 9039 and 3087. For methicillin-resistant S. aureus 667 and 2878, the equivalent effective doses of levofloxacin (once a day) were less than those of ciprofloxacin (twice a day) by 4.1 and 6.4 times, respectively. In a separate study, histological examination of all infected, untreated mice showed moderate to marked hematogenous pyelonephritis. Levofloxacin-treated mice (40 mg/kg once a day) showed no evidence of pyelonephritis in the kidneys, whereas the kidneys of mice treated with the same dose of ciprofloxacin showed only a reduction in the severity of the lesions. Treatment with ciprofloxacin (80 mg/kg twice a day) demonstrated a histology comparable to that of treatment with levofloxacin (40 mg/kg once a day). Levofloxacin (40 mg/kg once a day) reduced the log10 numbers of CFU per gram by 5 log10; however, ciprofloxacin (80 mg/kg twice a day) reduced the numbers of CFU per gram by only 3 log10. In the present murine model of pyelonephritis, levofloxacin was superior to ciprofloxacin in preventing pyelonephritis and eradicating S. aureus.


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