Development of Broad-Spectrum Antibiofilm Drugs: Strategies and Challenges

Dharmaprakash, Akhilandeswarre; Ramamurthy, Thandavarayan; Joseph, Iype; Thomas, Sabu

doi:10.2217/fmb.15.14

Cited by 11 publications

(10 citation statements)

References 108 publications

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“…Further, microbroth dilution and AB assays showed the non-bactericidal nature of UMB (Figure 2). This non-lethal effect of UMB on MRSE is expected to have reduced probabilities of drug resistance development, since killing effect of a drug is stated to aid in drug resistance by triggering Darwinian selection pressure on microbes (McCann et al, 2008; Dharmaprakash et al, 2015). With these observations, 500 μg/ml of UMB was fixed as MBIC and used for subsequent bioassays.…”

Section: Discussionmentioning

confidence: 99%

Umbelliferone Impedes Biofilm Formation and Virulence of Methicillin-Resistant Staphylococcus epidermidis via Impairment of Initial Attachment and Intercellular Adhesion

Swetha

Pooranachithra

Ganapathy

et al. 2019

Front. Cell. Infect. Microbiol.

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Staphylococcus epidermidis is an opportunistic human pathogen, which is involved in numerous nosocomial and implant associated infections. Biofilm formation is one of the prime virulence factors of S. epidermidis that supports its colonization on biotic and abiotic surfaces. The global dissemination of three lineages of S. epidermidis superbugs highlights its clinical significance and the imperative need to combat its pathogenicity. Thus, in the current study, the antibiofilm activity of umbelliferone (UMB), a natural product of the coumarin family, was assessed against methicillin-resistant S. epidermidis (MRSE). UMB exhibited significant antibiofilm activity (83%) at 500 μg/ml concentration without growth alteration. Microscopic analysis corroborated the antibiofilm potential of UMB and unveiled its potential to impair intercellular adhesion, which was reflected in auto-aggregation and solid phase adherence assays. Furthermore, real time PCR analysis revealed the reduced expression of adhesion encoding genes (icaD, atlE, aap, bhp, ebh, sdrG, and sdrF). Down regulation of agrA and reduced production of secreted hydrolases upon UMB treatment were speculated to hinder invasive lifestyle of MRSE. Additionally, UMB hindered slime synthesis and biofilm matrix components, which were believed to augment antibiotic susceptibility. In vivo assays using Caenorhabditis elegans divulged the non-toxic nature of UMB and validated the antibiofilm, antivirulence, and antiadherence properties of UMB observed in in vitro assays. Thus, UMB impairs MRSE biofilm by turning down the initial attachment and intercellular adhesion. Altogether, the obtained results suggest the potent antibiofilm activity of UMB and the feasibility of using it in clinical settings for combating S. epidermidis infections.

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Section: Discussionmentioning

confidence: 99%

Umbelliferone Impedes Biofilm Formation and Virulence of Methicillin-Resistant Staphylococcus epidermidis via Impairment of Initial Attachment and Intercellular Adhesion

Swetha

Pooranachithra

Ganapathy

et al. 2019

Front. Cell. Infect. Microbiol.

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“…Antibiotics refer to drugs that kill the microorganisms or inhibit the growth of these microorganisms. The use of antimicrobial drugs saved numerous lives and resulted in less morbidity from different infections [1][2][3]. Nevertheless, bacteria start developing resistance to the antibiotics.…”

Section: Introductionmentioning

confidence: 99%

The Rate of Adherence to Antibiotics and Reasons for Non-adherence among the Public

Ahmed

2020

JPRI

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Aim: Poor adherence to antibiotics is common and related to poorer clinical outcomes such as increasing the bacterial resistance. To explore the rate of adherence to antibiotics and to know the reasons that lead to antibiotic non-adherence among the public. Methodology: This is a retrospective study include an online questionnaire survey for the participants who were prescribed oral antimicrobial drugs during the last year. The data was collected and analyzed using Excel sheet software and the Descriptive data were presented by frequencies and percentages. Results: The majority of the respondents stated that they sometimes forget to take their antibiotics. Moreover, 78.3% of them said that sometimes they forget to carry their drugs when they go out. They reported many reasons for noncompliance but the major reasons were “they do not need to continue treatment once the condition improves” followed by “they are too busy in study or work”. Conclusion: Numerous factors lead to antibiotic noncompliance, but the main reasons were related to the public knowledge and attitude. Therefore, antimicrobial stewardship programs should focus on the patient education to solve the problem of non-compliance.

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“…Clinical application of antimicrobial drugs has reduced morbidity from infectious diseases and saved countless lives. [1][2][3] Incorrect use and abuse of antibiotic agents are key drivers of the spread of antimicrobial drug resistance. Antimicrobial drug resistance is a key concern while instituting therapy for bacterial infections.…”

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confidence: 99%