The Role of Orientation of Surface Bound Dihydropyrrol-2-ones (DHP) on Biological Activity

Quorum sensing (QS) signaling system is important for bacterial growth, adhesion, and biofilm formation resulting in numerous infectious diseases. Dihydropyrrol-2-ones (DHPs) represent a novel class of antimicrobial agents that inhibit QS, and are less prone to develop bacterial resistance due to their non-growth inhibition mechanism of action which does not cause survival pressure on bacteria. DHPs can prevent bacterial colonization and quorum sensing when covalently bound to substrates. In this study, the role of orientation of DHP compounds was investigated after covalent attachment by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling reaction to amine-functionalized glass surfaces via various positions of the DHP scaffold. The functionalized glass surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and contact angle measurements and tested for their in vitro biological activity against S. aureus and P. aeruginosa. DHPs attached via the N-1 position resulted in the highest antibacterial activities against S. aureus, while no difference was observed for DHPs attached either via the N-1 position or the C-4 phenyl ring against P. aeruginosa.

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Study of the Regulatory Role of N-Acyl Homoserine Lactones Mediated Quorum Sensing in the Biological Activity of Burkholderia gladioli pv. agaricicola Causing Soft Rot of Agaricus spp.

Frontiers in Microbiology ◽

10.3389/fmicb.2019.02695 ◽

2019 ◽

Vol 10 ◽

Author(s):

Hazem S. Elshafie ◽

Giulia Devescovi ◽

Vittorio Venturi ◽

Ippolito Camele ◽

Sabino A. Bufo

Keyword(s):

Biological Activity ◽

Quorum Sensing ◽

Soft Rot ◽

Regulatory Role ◽

Homoserine Lactones ◽

Acyl Homoserine Lactones ◽

Burkholderia Gladioli

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Covalent Graft of Lipopeptides and Peptide Dendrimers to Cellulose Fibers

Coatings ◽

10.3390/coatings9100606 ◽

2019 ◽

Vol 9 (10) ◽

pp. 606 ◽

Cited By ~ 2

Author(s):

Andrea Orlandin ◽

Paolo Dolcet ◽

Barbara Biondi ◽

Geta Hilma ◽

Diana Coman ◽

...

Keyword(s):

Photoelectron Spectroscopy ◽

Antimicrobial Agents ◽

Cellulose Fibers ◽

Specific Weight ◽

Amide Bond ◽

Covalent Attachment ◽

Peptide Dendrimers ◽

Two Samples ◽

Covalently Linked ◽

Peptide Functionalization

Introduction: Bacterial proliferation in health environments may lead to the development of specific pathologies, but can be highly dangerous under particular conditions, such as during chemotherapy. To limit the spread of infections, it is helpful to use gauzes and clothing containing antibacterial agents. As cotton tissues are widespread in health care environments, in this contribution we report the preparation of cellulose fibers characterized by the covalent attachment of lipopeptides as possible antimicrobial agents. Aim: To covalently link peptides to cotton samples and characterize them. Peptides are expected to preserve the features of the fabrics even after repeated washing and use. Peptides are well tolerated by the human body and do not induce resistance in bacteria. Materials and Methods: A commercially available cotton tissue (specific weight of 150 g/m2, 30 Tex yarn fineness, fabric density of 270/230 threads/10 cm in the warp and weft) was washed with alkali and bleached and died. A piece of this tissue was accurately weighed, washed with methanol (MeOH) and N,N-dimethylformamide (DMF), and air-dried. Upon incubation with epibromohydrin, followed by treatment with Fmoc-NH-CH2CH2-NH2 and Fmoc removal, the peptides were synthesized by incorporating one amino acid at a time, beginning with the formation of an amide bond with the free NH2 of 1,2–diaminoethane. We also linked to the fibers a few peptide dendrimers, because the mechanism of action of these peptides often requires the formation of clusters. We prepared and characterized seven peptide-cotton samples. Results: The new peptide-cotton conjugates were characterized by means of FT-IR spectroscopy and X-ray Photoelectron Spectroscopy (XPS). This latter technique allows for discriminating among different amino acids and thus different peptide-cotton samples. Some samples maintain a pretty good whiteness degree even after peptide functionalization. Interestingly, these samples also display encouraging activities against a Gram positive strain. Conclusions: Potentially antimicrobial lipopeptides can be covalently linked to cotton fabrics, step-by-step. It is also possible to build on the cotton Lys-based dendrimers. XPS is a useful technique to discriminate among different types of nitrogen. Two samples displaying some antibacterial potency did also preserve their whiteness index.

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The role of reactive oxygen species in the biological activity of antimicrobial agents: An updated mini review

Chemico-Biological Interactions ◽

10.1016/j.cbi.2020.109023 ◽

2020 ◽

Vol 320 ◽

pp. 109023 ◽

Cited By ~ 6

Author(s):

P.-L. Lam ◽

R.S.-M. Wong ◽

K.-H. Lam ◽

L.-K. Hung ◽

M.-M. Wong ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Biological Activity ◽

Antimicrobial Agents ◽

Reactive Oxygen ◽

Oxygen Species

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Quorum Sensing Regulation as a Target for Antimicrobial Therapy

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666211202115259 ◽

2021 ◽

Vol 21 ◽

Author(s):

Caterine Henríquez Ruiz ◽

Estefanie Osorio-Llanes ◽

Mayra Hernández Trespalacios ◽

Evelyn Mendoza-Torres ◽

Wendy Rosales ◽

...

Keyword(s):

Quorum Sensing ◽

Molecular Mechanisms ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Bacterial Species ◽

Cell Communication ◽

Structural Evolution ◽

Structural Diversity ◽

Signal Molecules ◽

Bacterial Survival

: Some bacterial species use a cell-to-cell communication mechanism called Quorum Sensing (QS). Bacteria release small diffusible molecules, usually termed signals which allow the activation of beneficial phenotypes that guarantee bacterial survival and the expression of a diversity of virulence genes in response to an increase in population density. The study of the molecular mechanisms that relate signal molecules with bacterial pathogenesis is an area of growing interest due to its use as a possible therapeutic alternative through the development of synthetic analogues of autoinducers as a strategy to regulate bacterial communication as well as the study of bacterial resistance phenomena, the study of these relationships is based on the structural diversity of natural or synthetic autoinducers and their ability to inhibit bacterial QS, which can be approached with a molecular perspective from the following topics: i) Molecular signals and their role in QS regulation; ii) Strategies in the modulation of Quorum Sensing; iii) Analysis of Bacterial QS circuit regulation strategies; iv) Structural evolution of natural and synthetic autoinducers as QS regulators. This mini-review allows a molecular view of the QS systems, showing a perspective on the importance of the molecular diversity of autoinducer analogs as a strategy for the design of new antimicrobial agents.

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Intranasal Septal Splints: Prophylactic Antibiotics and Nasal Microbiology

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489419867976 ◽

2019 ◽

Vol 129 (1) ◽

pp. 5-11

Author(s):

Amit Ritter ◽

Uri Alkan ◽

Dafna Yahav ◽

Ethan Soudry ◽

Ella Reifen

Keyword(s):

Antibiotic Prophylaxis ◽

Bacterial Resistance ◽

Bacterial Colonization ◽

Prophylactic Antibiotic ◽

Prophylactic Antibiotic Therapy ◽

Prophylactic Antibiotic Treatment ◽

Resistant Strains ◽

Accepted Practice ◽

Type Strains

Objectives: Intranasal septal splints are often used in nasal septal surgeries. Routine use of postoperative antibiotics is an accepted practice, although data regarding its efficacy in preventing postsurgical complications are limited. This study aimed to examine bacterial colonization on septal splints following prophylactic antibiotic therapy and the association with postoperative infections. Methods: Fifty-five patients underwent septoplasty by a single surgeon between March 2015 and April 2016. All had intranasal septal splints and were given antibiotic prophylaxis for 7 days until removal of splints. Nasal cultures were taken before surgery, and septal splints were examined for bacterial colonization following their removal. Results: Thirty-six patients (65%) had positive nasal culture prior to surgery. The most common isolates were Staphylococcus aureus (30%) and Enterobacteriaceae species (66%). All these patients had postoperative bacterial colonization on septal splints. In 15 patients with negative preoperative cultures, bacteria were isolated postoperatively. An increased resistance profile was documented postoperatively in 9 patients (16%), including two with multidrug resistance. In two of these patients preoperative wild-type strains acquired antibiotic resistance postoperatively. No adverse drug reactions to antibiotics were reported. Conclusions: Increased bacterial growth and emergence of resistant strains were observed on intranasal septal splints despite prophylactic antibiotic treatment. Nonetheless, this did not translate into clinical infection. Thus, considering antibiotics overuse and increasing bacterial resistance, further research is needed to determine the role of antibiotic prophylaxis in the setting of intranasal splints.

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Biodegradable Polymeric Micro/Nano-Structures with Intrinsic Antifouling/Antimicrobial Properties: Relevance in Damaged Skin and Other Biomedical Applications

Journal of Functional Biomaterials ◽

10.3390/jfb11030060 ◽

2020 ◽

Vol 11 (3) ◽

pp. 60 ◽

Cited By ~ 3

Author(s):

Mario Milazzo ◽

Giuseppe Gallone ◽

Elena Marcello ◽

Maria Donatella Mariniello ◽

Luca Bruschini ◽

...

Keyword(s):

Biomedical Applications ◽

Bacterial Resistance ◽

Bacterial Colonization ◽

Antimicrobial Properties ◽

Breast Implants ◽

Skin Damage ◽

Nano Structures ◽

Inner Organs ◽

Healthcare Associated

Bacterial colonization of implanted biomedical devices is the main cause of healthcare-associated infections, estimated to be 8.8 million per year in Europe. Many infections originate from damaged skin, which lets microorganisms exploit injuries and surgical accesses as passageways to reach the implant site and inner organs. Therefore, an effective treatment of skin damage is highly desirable for the success of many biomaterial-related surgical procedures. Due to gained resistance to antibiotics, new antibacterial treatments are becoming vital to control nosocomial infections arising as surgical and post-surgical complications. Surface coatings can avoid biofouling and bacterial colonization thanks to biomaterial inherent properties (e.g., super hydrophobicity), specifically without using drugs, which may cause bacterial resistance. The focus of this review is to highlight the emerging role of degradable polymeric micro- and nano-structures that show intrinsic antifouling and antimicrobial properties, with a special outlook towards biomedical applications dealing with skin and skin damage. The intrinsic properties owned by the biomaterials encompass three main categories: (1) physical–mechanical, (2) chemical, and (3) electrostatic. Clinical relevance in ear prostheses and breast implants is reported. Collecting and discussing the updated outcomes in this field would help the development of better performing biomaterial-based antimicrobial strategies, which are useful to prevent infections.

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Meta-Analysis of the Adverse Effects of Long-Term Azithromycin Use in Patients with Chronic Lung Diseases

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02067-13 ◽

2013 ◽

Vol 58 (1) ◽

pp. 511-517 ◽

Cited By ~ 30

Author(s):

Hui Li ◽

Ding-Hui Liu ◽

Lu-Lu Chen ◽

Qi Zhao ◽

Yan-Zhe Yu ◽

...

Keyword(s):

Adverse Effects ◽

Adverse Events ◽

Lung Diseases ◽

Bacterial Resistance ◽

Bacterial Colonization ◽

Meta Analysis ◽

Placebo Treatment ◽

Chronic Lung Diseases

ABSTRACTThe adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use.

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Potential Role of Pharmacokinetics, Pharmacodynamics, and Computerized Databases in Controlling Bacterial Resistance

Infection Control and Hospital Epidemiology ◽

10.1086/503169 ◽

2000 ◽

Vol 21 (S1) ◽

pp. S18-S21 ◽

Cited By ~ 8

Author(s):

Judith M. Hyatt ◽

Jerome J. Schentag

Keyword(s):

Potential Role ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Resistance Mechanisms ◽

Bacterial Isolation ◽

Ciprofloxacin Resistance ◽

Antibiotic Cycling ◽

The Impact ◽

Emergence Of Resistance

AbstractBacterial resistance to antibiotics continues to be a problem, in spite of increased knowledge of resistance mechanisms. Due to the multifactorial nature of bacterial resistance, studies that evaluate the association between antimicrobial exposure and emergence of resistance may fail to find a relationship unless other factors, in particular the association between patient-pathogen pharmacokinetics (PK) and pharmacodynamics (PD) and the emergence of bacterial resistance, are evaluated as well. It has been hypothesized that, in conjunction with good infection control practices, cycling of antimicrobial agents may prove to be effective in reducing resistance emergence.There is some indication that there may be a relationship between the level of antibiotic exposure and the probability of emergence of bacterial resistance. As shown in our companion article in this supplement, factors associated with ciprofloxacin resistance in Pseudomonas aeruginosa included increased length of stay prior to isolation, exposure to ciprofloxacin, and respiratory tract site of bacterial isolation. However, in patients who received ciprofloxacin therapy, when exposure was at an area under the 24-hour inhibitory concentration curve (AUIC24)>110 (μg·h/mL)/μg/mL, resistance was decreased to 11%, a rate similar to that seen in respiratory isolates not exposed to ciprofloxacin (7%).While the length of time the patient spends in the hospital and the site of infection cannot be controlled, by using PK and PD principles for dosing of ciprofloxacin, the emergence of ciprofloxacin resistance in P aeruginosa may be reduced. Prospective antibiotic-cycling studies may help to determine not only the impact of antibiotic cycling on the institution's antibiogram but also, through the use of PK and PD principles, may help to determine appropriate dosing schedules for antibiotics in order to reduce the probability of emergence of bacterial resistance.

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