scholarly journals Antimicrobial Activity of Nanoconjugated Glycopeptide Antibiotics and Their Effect on Staphylococcus aureus Biofilm

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Berini ◽  
Viviana Teresa Orlandi ◽  
Federica Gamberoni ◽  
Eleonora Martegani ◽  
Ilaria Armenia ◽  
...  

In the era of antimicrobial resistance, the use of nanoconjugated antibiotics is regarded as a promising approach for preventing and fighting infections caused by resistant bacteria, including those exacerbated by the formation of difficult-to-treat bacterial biofilms. Thanks to their biocompatibility and magnetic properties, iron oxide nanoparticles (IONPs) are particularly attractive as antibiotic carriers for the targeting therapy. IONPs can direct conjugated antibiotics to infection sites by the use of an external magnet, facilitating tissue penetration and disturbing biofilm formation. As a consequence of antibiotic localization, a decrease in its administration dosage might be possible, reducing the side effects to non-targeted organs and the risk of antibiotic resistance spread in the commensal microbiota. Here, we prepared nanoformulations of the ‘last-resort’ glycopeptides teicoplanin and vancomycin by conjugating them to IONPs via surface functionalization with (3-aminopropyl) triethoxysilane (APTES). These superparamagnetic NP-TEICO and NP-VANCO were chemically stable and NP-TEICO (better than NP-VANCO) conserved the typical spectrum of antimicrobial activity of glycopeptide antibiotics, being effective against a panel of staphylococci and enterococci, including clinical isolates and resistant strains. By a combination of different methodological approaches, we proved that NP-TEICO and, although to a lesser extent, NP-VANCO were effective in reducing biofilm formation by three methicillin-sensitive or resistant Staphylococcus aureus strains. Moreover, when attracted and concentrated by the action of an external magnet, NP-TEICO exerted a localized inhibitory effect on S. aureus biofilm formation at low antibiotic concentration. Finally, we proved that the conjugation of glycopeptide antibiotics to IONPs reduced their intrinsic cytotoxicity toward a human cell line.

RSC Advances ◽  
2019 ◽  
Vol 9 (56) ◽  
pp. 32453-32461
Author(s):  
Yan-Ping Wu ◽  
Xiao-Yan Liu ◽  
Jin-Rong Bai ◽  
Hong-Chen Xie ◽  
Si-Liang Ye ◽  
...  

3-p-trans-Coumaroyl-2-hydroxyquinic acid (CHQA), a natural phenolic compound, prevented Staphylococcus aureus biofilm formation due to the inhibition of the initial attachment stage of biofilm development by targeting sortase A.


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.


2019 ◽  
Author(s):  
Jenish Shakya ◽  
Bijay Kumar Shrestha ◽  
Prince Subba ◽  
Hemanta Khanal

Abstract Background Staphylococcus aureus is one of the common cause of hospital acquired infection and community acquired infections. Nowadays these organisms became resistant towards variety of drugs. MRSA is the emerging antibiotic resistant bacteria that are resistant to methicillin antibiotic and known to be the infectious pathogen causing severe infection and a cause of fatal mortality.Materials and methodology Altogether 200 nasal swabs and 200 hand swabs were obtained from participants and transported to microbiology lab in cold chain. The samples were swabbed in mannitol salt agar (MSA) containing oxacillin powder of 6mg/L and incubated at 37°C for 24 hrs. Staphylococcus aureus colonies were identified based on growth characteristics on MSA plates (golden yellow colonies), Gram stain and positive results for coagulase tube test and catalase test. The pure isolated MRSA were subjected to antibiotic susceptibility tests and biofilm formation assays.Results From our study the overall prevalence of CA-MRSA was 61.5%. Higher frequency of multi-drug resistant MRSA was isolated. The biofilm producing CA-MRSA were 51.2% which showed high drug resistance and rest (48.7%) were non-biofilm producers. There was significant association in biofilm production with multi-drug resistance (p<0.05). Ciprofloxacin was most sensitive drug against the isolates which was statistically significant (p<0.05). The resistant pattern of biofilm producers reported high ability of multi-drug resistance compared to non-biofilm producers (p<0.05). Microtitre plate method was found to be gold standard over tube and congo red agar method for screening biofilm formation. Surprisingly the emergence of VISA and VRSA strains were significantly reported from our study. The prevalence of VISA and VRSA among CA-MRSA was found to be 49.5% and 40.6% respectively among the isolates which indicates the failure of Vancomycin drug in clinical therapy.Conclusions The prevalence of CA-MRSA was found more in barbers followed by beauticians and municipal waste workers in comparison to healthy controls. This study reported the higher carriage of CA-MRSA in potential risk population along with emergence of VISA and VRSA strains. Improvement in personal hygiene and formulation of appropriate health policy helps to prevent CA-MRSA infection. This study concludes that CA-MRSA is still emerging with multi-drug resistance.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249547
Author(s):  
Yu Luo ◽  
Daniel F. McAuley ◽  
Catherine R. Fulton ◽  
Joana Sá Pessoa ◽  
Ronan McMullan ◽  
...  

Polymicrobial biofilms consisting of fungi and bacteria are frequently formed on endotracheal tubes and may contribute to development of ventilator associated pneumonia (VAP) in critically ill patients. This study aimed to determine the role of early Candida albicans biofilms in supporting dual-species (dual-kingdom) biofilm formation with respiratory pathogens in vitro, and investigated the effect of targeted antifungal treatment on bacterial cells within the biofilms. Dual-species biofilm formation between C. albicans and three respiratory pathogens commonly associated with VAP (Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus) was studied using quantitative PCR. It was shown that early C. albicans biofilms enhanced the numbers of E. coli and S. aureus (including methicillin resistant S. aureus; MRSA) but not P. aeruginosa within dual-species biofilms. Transwell assays demonstrated that contact with C. albicans was required for the increased bacterial cell numbers observed. Total Internal Reflection Fluorescence microscopy showed that both wild type and hyphal-deficient C. albicans provided a scaffold for initial bacterial adhesion in dual species biofilms. qPCR results suggested that further maturation of the dual-species biofilm significantly increased bacterial cell numbers, except in the case of E.coli with hyphal-deficient C. albicans (Ca_gcn5Δ/Δ). A targeted preventative approach with liposomal amphotericin (AmBisome®) resulted in significantly decreased numbers of S. aureus in dual-species biofilms, as determined by propidium monoazide-modified qPCR. Similar results were observed when dual-species biofilms consisting of clinical isolates of C. albicans and MRSA were treated with liposomal amphotericin. However, reductions in E. coli numbers were not observed following liposomal amphotericin treatment. We conclude that early C. albicans biofilms have a key supporting role in dual-species biofilms by enhancing bacterial cell numbers during biofilm maturation. In the setting of increasing antibiotic resistance, an important and unexpected consequence of antifungal treatment of dual-species biofilms, is the additional benefit of decreased growth of multi-drug resistant bacteria such as MRSA, which could represent a novel future preventive strategy.


2018 ◽  
Vol 13 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Liang Peng ◽  
Yunhao Xiong ◽  
Mei Wang ◽  
Manman Han ◽  
Weilan Cai ◽  
...  

AbstractThe essential oil of Mosla chinensis Maxim cv. Jiangxiangru is known for its antibacterial ability. This study aimed to investigate the chemical composition of Jiangxiangru essential oil and its inhibitory effect on Staphylococcus aureus biofilm formation. Gas chromatography/mass spectrometry (GC–MS) was used to determine the chemical composition of Jiangxiangru essential oil. Subsequently, the eight major chemical components were quantitatively analyzed using GC– MS, and their minimum inhibitory concentration (MIC) values against S. aureus were tested. Biofilm formation was detected by crystal violet semi-quantitative method and silver staining. Of the 59 peaks detected, 29 were identified by GC–MS. Of these peaks, thymol, carvacrol, p-cymene, γ-terpinene, thymol acetate, α-caryophyllene, 3-carene, and carvacryl acetate were present at a relatively higher concentration. The results of the quantitative test showed that thymol, carvacrol, p-cymene, and γ-terpinene were the major components of the essential oil. Among the eight reference substances, only thymol, carvacrol, and thymol acetate had lower MICs compared with the essential oil. Essential oil, carvacrol, carvacryl acetate, α-caryophyllene, and 3-carene showed the better inhibition of S. aureus biofilm formation. When one fourth of the MIC concentrations were used for these substances (0.0625 mg/mL for essential oil, 0.0305 mg/mL for carvacrol, 1.458 mg/mL for carvacryl acetate, 0.1268 mg/mL for α-caryophyllene, and 2.5975 mg/mL for 3-carene), the inhibition rates were over 80%. However, thymol, γ-terpinene, thymol acetate, and p-cymene showed a relatively poor inhibition of S. aureus biofilm formation. When 1× MIC concentrations of these substances were used, the inhibition rates were less than 50%. In conclusion, Jiangxiangru essential oil and its major components, carvacrol, carvacryl acetate, α-caryophyllene, and 3-carene, strongly inhibited biofilm formation in S. aureus.


2020 ◽  
Vol 21 (16) ◽  
pp. 5632
Author(s):  
Jong-Kook Lee ◽  
Yoonkyung Park

Novel antibiotic drugs are urgently needed because of the increase in drug-resistant bacteria. The use of antimicrobial peptides has been suggested to replace antibiotics as they have strong antimicrobial activity and can be extracted from living organisms such as insects, marine organisms, and mammals. HPA3NT3-A2 ([Ala1,8] HPA3NT3) is an antimicrobial peptide that is an analogue of the HP (2–20) peptide derived from Helicobacter pylori ribosomal protein L1. Although this peptide was shown to have strong antimicrobial activity against drug-resistant bacteria, it also showed lower toxicity against sheep red blood cells (RBCs) and HaCaT cells compared to HPA3NT3. The l-Lys residues of HPA3NT3-A2 was substituted with d-Lys residues (HPA3NT3-A2D; [d-Lys2,5,6,9,10,15] HPA3NT3-A2) to prevent the cleavage of peptide bonds by proteolytic enzymes under physiological conditions. This peptide showed an increased half-life and maintained its antimicrobial activity in the serum against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) (pathogen). Furthermore, the antimicrobial activity of HPA3NT3-A2D was not significantly affected in the presence of mono- or divalent ions (Na+, Mg2+, Ca2+). Finally, l- or d-HPA3NT3-A2 peptides exhibited the strongest antimicrobial activity against antibiotic-resistant bacteria and failed to induce resistance in Staphylococcus aureus after 12 passages.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hellen Braga Martins Oliveira ◽  
Nathan das Neves Selis ◽  
Beatriz Almeida Sampaio ◽  
Manoel Neres Santos Júnior ◽  
Suzi Pacheco de Carvalho ◽  
...  

AbstractMethicillin-resistant Staphylococcus aureus (MRSA) is responsible for high morbidity and mortality rates. Citral has been studied in the pharmaceutical industry and has shown antimicrobial activity. This study aimed to analyze the antimicrobial activity of citral in inhibiting biofilm formation and modulating virulence genes, with the ultimate goal of finding a strategy for treating infections caused by MRSA strains. Citral showed antimicrobial activity against MRSA isolates with minimum inhibitory concentration (MIC) values between 5 mg/mL (0.5%) and 40 mg/mL (4%), and minimum bactericidal concentration (MBC) values between 10 mg/mL (1%) and 40 mg/mL (4%). The sub-inhibitory dose was 2.5 mg/mL (0.25%). Citral, in an antibiogram, modulated synergistically, antagonistically, or indifferent to the different antibiotics tested. Prior to evaluating the antibiofilm effects of citral, we classified the bacteria according to their biofilm production capacity. Citral showed greater efficacy in the initial stage, and there was a significant reduction in biofilm formation compared to the mature biofilm. qPCR was used to assess the modulation of virulence factor genes, and icaA underexpression was observed in isolates 20 and 48. For icaD, seg, and sei, an increase was observed in the expression of ATCC 33,591. No significant differences were found for eta and etb. Citral could be used as a supplement to conventional antibiotics for MRSA infections.


2019 ◽  
Author(s):  
God’spower Bello-Onaghise ◽  
Xing Xiaoxu ◽  
Zhou Yonghui ◽  
Qu Qianwei ◽  
Cui Wenqiang ◽  
...  

ABSTRACTThe biofilm of bacteria plays an important role in antibiotic resistance and chronic infection. Thus, in order to solve the problem of resistant bacteria, it is very important to find new drugs that can inhibit the formation of biofilms. In recent years, researchers have shifted their attention to natural products. As a flavonoid, rutin has been reported to have a variety of biological activities, interestingly, in this study, the inhibitory effect of rutin on the biofilm of Staphylococcus xylosus was investigated. We confirmed that rutin could effectively inhibit the biofilm formation of S. xylosus, then, for the sake of discussion on how it interferes with the biofilm formation, the interaction between rutin and imidazolyl phosphate dehydratase (IGPD) which has been identified as the key enzyme that plays a vital role in the process of biofilm formation was analyzed by molecular docking, the results showed that rutin had a strong affinity with IGPD, it occupied the hydrophobic cavity of the active center forming four hydrogen bonds and many other interactions. In addition, we proved that rutin was able to combine with IGPD using SPR technique. Therefore, we determined the enzyme activity and histidine content of IGPD, the result indicated that rutin could simultaneously inhibit the activity of IGPD and abrogate the synthesis of histidine. Interestingly, the hisB gene encoding for IGPD and IGPD in S. xylosus were also significantly inhibited when the bacterial culture was treated with rutin. Taken together, the results have provided evidence that rutin is a natural drug that has the ability to interfere with the formation of biofilm in S. xylosus. It is therefore a potential enzyme inhibitor of IGPD.Author’s SummaryStaphylococcus xylosus has been isolated from a variety of infections, and the biofilm formed by S. xylosus can help the bacteria evade the immune system of the host and cause chronic infections. Here, we dealt with this menace by establishing a highly effective drug with the ability to interfere with the process involved in the formation of biofilm in S. xylosus. IGPD has been reported to be directly involved in the formation of biofilm in Staphylococcus xylosus and it is known to be present in a variety of microorganisms. Based on this study, we developed a drug therapy targeting IGPD and at the same time interfere with the formation of biofilm in S. xylosus


2020 ◽  
Vol 10 (4) ◽  
pp. 44-48
Author(s):  
Nihed BARGHOUT ◽  
Nada CHEBATA ◽  
Saida MOUMENE ◽  
Seddik KHENNOUF ◽  
Abdelaziz GHARBI ◽  
...  

Polianthes tuberosa L. (Amaryllidaceae) is an ornamental and medicinal plant. Its flowers and bulbs are used traditionally as a diuretic, emetic, against rashes and gonorrhea. The aim of this work was, to evaluate the antioxidant and antimicrobial activities of bulbs and bulbils alkaloid extracts of P. tuberosa. Antiradical effect was assessed against DPPH radical. However, antimicrobial activity was measured through the disc diffusion method against Escherichae coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Staphylococcus aureus resistant to Methicillin (MRSA) and Candida albicans ATCC 90028. The scavenging effect against DPPH showed that the bulbs and bulbils alkaloids extracts exhibited an antiradical effect with IC50 = 0.231±0.017 mg/mL and 0.233±0.093 mg/mL respectively, less than the effect of vitamin C with IC50 = 0.0194±0.0002 mg/mL. Antimicrobial activity results reveal that both alkaloid bulbs extracts at 50 mg/mL did not have any inhibitory effect against the studied strains using the disc diffusion method. According to this work, bulbs and bulbils alkaloid extracts show a moderate antioxidant effect; that could be recommended as a natural antioxidant. Although tuberose bulbs were used traditionally as a soap substitute; bulbs alkaloid extract has no antimicrobial effect. Keywords: Polianthes tuberosa L., bulbs, bulbils, alkaloids, antiradical activity, antimicrobial activity.


2018 ◽  
Vol 15 (8) ◽  
pp. 475-480 ◽  
Author(s):  
Yan-Ping Wu ◽  
Jin-Rong Bai ◽  
Elena Grosu ◽  
Kai Zhong ◽  
Li-Jin Liu ◽  
...  

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