scholarly journals The Principles, Mechanisms, and Benefits of Unconventional Agents in the Treatment of Biofilm Infection

2020 ◽  
Vol 13 (10) ◽  
pp. 299
Author(s):  
Jasminka Talapko ◽  
Ivana Škrlec
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Treatment Strategies ◽  
Cationic Peptides ◽  
Bacterial Cells ◽  
Infectious Agents ◽  
Severe Infections ◽  
Eskape Pathogens ◽  
Interdependent Relationships ◽  
Biofilm Infection

Today, researchers are looking at new ways to treat severe infections caused by resistance to standard antibiotic therapy. This is quite challenging due to the complex and interdependent relationships involved: the cause of infection–the patient–antimicrobial agents. The sessile biofilm form is essential in research to reduce resistance to very severe infections (such as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter spp). The purpose of this study is to elucidate the mechanisms of the occurrence, maintenance, and suppression of biofilm infections. One form of biofilm suppression is the efficient action of natural antagonists of bacteria—bacteriophages. Bacteriophages effectively penetrate the biofilm’s causative cells. They infect those bacterial cells and either destroy them or prevent the infection spreading. In this process, bacteriophages are specific, relatively easy to apply, and harmless to the patient. Antimicrobial peptides (AMPs) support the mechanisms of bacteriophages’ action. AMPs could also attack and destroy infectious agents on their own (even on biofilm). AMPs are simple, universal peptide molecules, mainly cationic peptides. Additional AMP research could help develop even more effective treatments of biofilm (bacteriophages, antibiotics, AMPs, nanoparticles). Here, we review recent unconventional agents, such as bacteriophages and AMPs, used for eradication of biofilm, providing an overview of potentially new biofilm treatment strategies.

scholarly journals Changes in the Ultrastructure of Staphylococcus aureus Treated with Cationic Peptides and Chlorhexidine

2020 ◽  
Vol 8 (12) ◽  
pp. 1991
Author(s):  
Alina Grigor’eva ◽  
Alevtina Bardasheva ◽  
Anastasiya Tupitsyna ◽  
Nariman Amirkhanov ◽  
Nina Tikunova ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Membrane ◽  
Antimicrobial Peptides ◽  
Membrane Damage ◽  
Observation Time ◽  
Resistant Bacteria ◽  
Cationic Peptides ◽  
Bacterial Cells ◽  
Cell Membrane Damage

Antimicrobial peptides, including synthetic ones, are becoming increasingly important as a promising tool to fight multidrug-resistant bacteria. We examined the effect of cationic peptides H2N-Arg9-Phe2-C(O)NH2 and H2N-(Lys-Phe-Phe)3-Lys-C(O)NH2 on Staphylococcus aureus, which remains one of the most harmful pathogens. Antiseptic chlorhexidine served as reference preparation. We studied viability of S. aureus and examined its ultrastructure under treatment with 100 µM of R9F2 or (KFF)3K peptides or chlorhexidine using transmission electron microscopy of ultrathin sections. Bacterial cells were sampled as kinetic series starting from 1 min up to 4 h of treatment with preparations. Both peptides caused clearly visible damage of bacteria cell membrane within 1 min. Incubation of S. aureus with R9F2 or (KFF)3K peptides led to cell wall thinning, loss of cytoplasm structure, formation of mesosome-derived multimembrane structures and “decorated fibers” derived from DNA chains. The effect of R9F2 peptides on S. aureus was more severe than the effect of (KFF)3K peptides. Chlorhexidine heavily damaged the bacteria cell wall, in particular in areas of septa formation, while cytoplasm kept its structure within the observation time. Our study showed that cell membrane damage is critical for S. aureus viability; however, we believe that cell wall disorders should also be taken into account when analyzing the effects of the mechanisms of action of antimicrobial peptides (AMPs).

Progress and Challenges in Implementing the Research on ESKAPE Pathogens

2010 ◽  
Vol 31 (S1) ◽  
pp. S7-S10 ◽  
Author(s):  
Louis B. Rice
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Optimal Strategies ◽  
Resistance Mechanisms ◽  
Antimicrobial Use ◽  
Individual Resistance ◽  
Population Science ◽  
Eskape Pathogens ◽  
Modern Hospital ◽  
The Impact

The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, andEnterobacterspecies) are responsible for a substantial percentage of nosocomial infections in the modern hospital and represent the vast majority of isolates whose resistance to antimicrobial agents presents serious therapeutic dilemmas for physicians. Over the years, improved molecular biology techniques have led to detailed information about individual resistance mechanisms in all these pathogens. However, there remains a lack of compelling data on the interplay between resistance mechanisms and between the bacteria themselves. In addition, data on the impact of clinical interventions to decrease the prevalence of resistance are also lacking. The difficulty in identifying novel antimicrobial agents with reliable activity against these pathogens argues for an augmentation of research in the basic and population science of resistance, as well as careful studies to identify optimal strategies for infection control and antimicrobial use.

scholarly journals Biofilm Matrix Exoproteins Induce a Protective Immune Response against Staphylococcus aureus Biofilm Infection

2013 ◽  
Vol 82 (3) ◽  
pp. 1017-1029 ◽  
Author(s):  
Carmen Gil ◽  
Cristina Solano ◽  
Saioa Burgui ◽  
Cristina Latasa ◽  
Begoña García ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Extracellular Proteins ◽  
Protective Immune Response ◽  
Surrounding Tissue ◽  
Bacterial Cells ◽  
Content Type ◽  
Biofilm Infection ◽  
Biofilm Matrix

ABSTRACTTheStaphylococcus aureusbiofilm mode of growth is associated with several chronic infections that are very difficult to treat due to the recalcitrant nature of biofilms to clearance by antimicrobials. Accordingly, there is an increasing interest in preventing the formation ofS. aureusbiofilms and developing efficient antibiofilm vaccines. Given the fact that during a biofilm-associated infection, the first primary interface between the host and the bacteria is the self-produced extracellular matrix, in this study we analyzed the potential of extracellular proteins found in the biofilm matrix to induce a protective immune response againstS. aureusinfections. By using proteomic approaches, we characterized the exoproteomes of exopolysaccharide-based and protein-based biofilm matrices produced by two clinicalS. aureusstrains. Remarkably, results showed that independently of the nature of the biofilm matrix, a common core of secreted proteins is contained in both types of exoproteomes. Intradermal administration of an exoproteome extract of an exopolysaccharide-dependent biofilm induced a humoral immune response and elicited the production of interleukin 10 (IL-10) and IL-17 in mice. Antibodies against such an extract promoted opsonophagocytosis and killing ofS. aureus. Immunization with the biofilm matrix exoproteome significantly reduced the number of bacterial cells inside a biofilm and on the surrounding tissue, using anin vivomodel of mesh-associated biofilm infection. Furthermore, immunized mice also showed limited organ colonization by bacteria released from the matrix at the dispersive stage of the biofilm cycle. Altogether, these data illustrate the potential of biofilm matrix exoproteins as a promising candidate multivalent vaccine againstS. aureusbiofilm-associated infections.

scholarly journals Pexiganan in Combination with Nisin to Control Polymicrobial Diabetic Foot Infections

Antibiotics ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 128 ◽  
Author(s):  
Diana Gomes ◽  
Raquel Santos ◽  
Rui S. Soares ◽  
Solange Reis ◽  
Sandra Carvalho ◽  
...  
Keyword(s):  
Diabetic Foot ◽  
Antimicrobial Agents ◽  
Guar Gum ◽  
Three Dimensional ◽  
Treatment Strategies ◽  
Complementary Therapy ◽  
Multidrug Resistant ◽  
Aureus Strain ◽  
Bacterial Cells ◽  
Diabetic Foot Infections

Diabetic foot ulcers (DFUs) are major complications of Diabetes mellitus being responsible for significant morbidity and mortality. DFUs frequently become chronically infected by a complex community of bacteria, including multidrug-resistant and biofilm-producing strains of Staphylococcus aureus and Pseudomonas aeruginosa. Diabetic foot infections (DFI) are often recalcitrant to conventional antibiotics and alternative treatment strategies are urgently needed. Antimicrobial Peptides (AMPs), such as pexiganan and nisin, have been increasingly investigated and reported as effective antimicrobial agents. Here, we evaluated the antibacterial potential of pexiganan and nisin used in combination (dual-AMP) to control the growth of planktonic and biofilm co-cultures of S. aureus and P. aeruginosa clinical strains, co-isolated from a DFU. A DFU collagen three-dimensional (3D) model was used to evaluate the distribution and efficacy of AMPs locally delivered into the model. The concentration of pexiganan required to inhibit and eradicate both planktonic and biofilm-based bacterial cells was substantially reduced when used in combination with nisin. Moreover, incorporation of both AMPs in a guar gum delivery system (dual-AMP biogel) did not affect the dual-AMP antimicrobial activity. Importantly, the application of the dual-AMP biogel resulted in the eradication of the S. aureus strain from the model. In conclusion, data suggest that the local application of the dual-AMPs biogel constitutes a potential complementary therapy for the treatment of infected DFU.

scholarly journals Staphylococcus aureus Biofilm: Morphology, Genetics, Pathogenesis and Treatment Strategies

2021 ◽  
Vol 18 (14) ◽  
pp. 7602
Author(s):  
Muhammad Idrees ◽  
Sheeba Sawant ◽  
Nazira Karodia ◽  
Ayesha Rahman
Keyword(s):  
Staphylococcus Aureus ◽  
Global Economy ◽  
Gene Evolution ◽  
Complex Structure ◽  
Genetic Material ◽  
Treatment Strategies ◽  
Host Immune System ◽  
Bacterial Cells ◽  
Antibacterial Drugs ◽  
Animal Populations

Staphylococcus aureus is a nosocomial bacterium causing different infectious diseases, ranging from skin and soft tissue infections to more serious and life-threatening infections such as septicaemia. S. aureus forms a complex structure of extracellular polymeric biofilm that provides a fully secured and functional environment for the formation of microcolonies, their sustenance and recolonization of sessile cells after its dispersal. Staphylococcus aureus biofilm protects the cells against hostile conditions, i.e., changes in temperature, limitations or deprivation of nutrients and dehydration, and, more importantly, protects the cells against antibacterial drugs. Drugs are increasingly becoming partially or fully inactive against S. aureus as they are either less penetrable or totally impenetrable due to the presence of biofilms surrounding the bacterial cells. Other factors, such as evasion of innate host immune system, genome plasticity and adaptability through gene evolution and exchange of genetic material, also contribute to the ineffectiveness of antibacterial drugs. This increasing tolerance to antibiotics has contributed to the emergence and rise of antimicrobial resistance (AMR), a serious problem that has resulted in increased morbidity and mortality of human and animal populations globally, in addition to causing huge financial losses to the global economy. The purpose of this review is to highlight different aspects of S. aureus biofilm formation and its overall architecture, individual biofilm constituents, clinical implications and role in pathogenesis and drug resistance. The review also discusses different techniques used in the qualitative and quantitative investigation of S. aureus biofilm and various strategies that can be employed to inhibit and eradicate S. aureus biofilm.

scholarly journals Multiple Low Frequency Ultrasound Enhances Bactericidal Activity of Vancomycin against Methicillin-ResistantStaphylococcus aureusBiofilms

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Jin Wang ◽  
Ke Wen ◽  
Xu Liu ◽  
Chun-xiao Weng ◽  
Rui Wang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Synergistic Effect ◽  
Antimicrobial Agents ◽  
Synergistic Effects ◽  
Low Frequency ◽  
Drug Concentrations ◽  
Broth Microdilution Method ◽  
Low Frequency Ultrasound ◽  
Biofilm Infection ◽  
Frequency Ultrasound

Methicillin-resistantStaphylococcus aureus(MRSA) biofilm infections are difficult to treat due to the high antimicrobial resistance of biofilm. Therefore, new treatments are needed for more effective bacteria clearance. This study was to investigate whether low frequency ultrasound (LFU) can enhance the activity of antimicrobial agents against MRSA biofilm infection. Broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of vancomycin (VAN), linezolid (LIN), and levofloxacin (LEV) against three clinical isolated strains, including one methicillin-susceptibleStaphylococcus aureus(MSSA) strain and two MRSA strains. Effects of various influencing factors, such as antimicrobial agents, drug concentrations, ultrasonic intensity, and single (S-LFU, 5 or 15 min) or multiple ultrasound (M-LFU, 5 min every 8 h), on the inhibition of biofilms were investigated. The bactericidal effects of S-LFU or M-LFU on MRSA or MSSA biofilms were determined by colony counts. Right after ultrasound, synergistic effects were observed in groups of S-LFU combined with three antimicrobial agents against MSSA biofilm, but for MRSA biofilm, only S-LFU plus VAN had synergistic effect. At the time point of 24 h, M-LFU plus VAN treatment had synergistic bactericidal effect against MRSA and MSSA biofilms, and the synergy showed that VAN is concentration-dependent, but no synergistic effects were observed in all S-LFU combination groups. In conclusion, combination of M-LFU and antimicrobial agents had a better synergistic effect than S-LFU against MRSA or MSSA biofilm. LFU may be useful in treating biofilm infection in the future.

scholarly journals In VitroActivities of Antibiotics and Antimicrobial Cationic Peptides Alone and in Combination against Methicillin-Resistant Staphylococcus aureus Biofilms

2012 ◽  
Vol 56 (12) ◽  
pp. 6366-6371 ◽  
Author(s):  
Emel Mataraci ◽  
Sibel Dosler
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Antibiofilm Activity ◽  
Cationic Peptides ◽  
Planktonic Cells ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Strains ◽  
Almost All

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains are most often found as hospital- and community-acquired infections. The danger of MRSA infections results from not only the emergence of multidrug resistance but also the occurrence of bacteria that form strong biofilms. We investigated thein vitroactivities of antibiotics (daptomycin, linezolid, teichoplanine, azithromycin, and ciprofloxacin) and antimicrobial cationic peptides {AMPs; indolicidin, CAMA [cecropin (1-7)–melittin A (2-9) amide], and nisin} alone or in combination against MRSA ATCC 43300 biofilms. The MICs and minimum biofilm eradication concentrations (MBECs) were determined by the broth microdilution technique. Antibiotic and AMP combinations were assessed using the checkerboard technique. For MRSA planktonic cells, MICs of antibiotics and AMPs ranged between 0.125 and 512 and 8 and 16 mg/liter, respectively, and the MBEC values were between 512 and 5,120 and 640 mg/liter, respectively. With a fractional inhibitory concentration of ≤0.5 as the borderline, synergistic interactions against MRSA biofilms were frequent with almost all antibiotic-antibiotic and antibiotic-AMP combinations. Against planktonic cells, they generally had an additive effect. No antagonism was observed. All of the antibiotics, AMPs, and their combinations were able to inhibit the attachment of bacteria at 1/10 MIC and biofilm formation at 1× MIC. Biofilm-associated MRSA was not affected by therapeutically achievable concentrations of antimicrobial agents. Use of a combination of antimicrobial agents can provide a synergistic effect, which rapidly enhances antibiofilm activity and may help prevent or delay the emergence of resistance. AMPs seem to be good candidates for further investigations in the treatment of MRSA biofilms, alone or in combination with antibiotics.

Homologous and heterologous adaptation and thermochemical inactivation of Staphylococcus aureus to cinnamaldehyde

2020 ◽  
Author(s):  
Luciana Vitorino ◽  
Tenille Ribeiro de Souza ◽  
Michelle Carlota Gonçalves ◽  
Letícia Andrade do Vale ◽  
Roberta Hilsdorf Piccoli
Keyword(s):  
Staphylococcus Aureus ◽  
Exposure Time ◽  
Antimicrobial Agents ◽  
Acid Stress ◽  
Bactericidal Effect ◽  
Adaptive Plasticity ◽  
Bacterial Cells ◽  
Positive Effect ◽  
Sublethal Concentrations ◽  
Antibacterial Potential

Staphylococcus aureus causes food intoxication and can become resistant to a large number of drugs. Thus, there is a growing interest in understanding the mechanisms involved in the adaptation of bacterial cells to environmental stresses or to antimicrobial agents. In this context, we evaluated the cinnamaldehyde (CIN) MBC for two contaminating food strains of S. aureus (GL 5674 and GL 8702) and tested the hypothesis that the exposure of these strains to sublethal concentrations of CIN and pH could increase their resistance to this antimicrobial, to acid stress and also to stress at high temperatures. Thus, the ability of the strains to adapt to CIN and acid stress was evaluated, as well as the cross adaptation between acid stress and CIN. The strains GL 5674 and GL 8702 of S. aureus are sensitive to CIN in MBCs of 0.25% and 0.5% respectively, proving the antibacterial potential of this compound, but we proved the hypothesis of homologous adaptation to CIN. The strains grew in concentrations higher than the MBC after being previously exposed to sublethal concentrations of CIN. It was also observed heterologous adaptation of the strains, which, after exposure to the minimum pH of growth, were able to grow in concentrations greater than the MBC of CIN. GL 5674 showed greater adaptive plasticity, considerably reducing its minimum inhibitory pH and increasing its MBC after adaptation. Our results show a positive effect of adaptation to CIN, on the resistance of S. aureus (p <0.0001) to CIN, at a temperature of 37 ° C. However, in the absence of adaptation, the presence of CIN in S. aureus cultures maintained at 37 ° C, associated with increased exposure time showed an efficient bactericidal effect. Our results call attention to the conscious use of CIN as an antimicrobial agent and presents the possibility of using CIN, associated with the temperature of 37 ºC and the exposure time of 35 min, as a promising measure for the elimination of pathogenic strains .

scholarly journals Tailoring nanoparticle-biofilm interactions to increase efficacy of antimicrobial agents against Staphylococcus aureus

2020 ◽  
Author(s):  
Henry Devlin ◽  
Stephanie Fulaz ◽  
Stefania Vitale ◽  
Laura Quinn ◽  
James O'Gara ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Mesoporous Silica Nanoparticles ◽  
Local Concentration ◽  
Bacterial Cells ◽  
Chronic Infections ◽  
Antimicrobial Drugs ◽  
Common Causes ◽  
Surface Functionalizations ◽  
Positively Charged

<p>Considering the timeline required for the development of novel antimicrobial drugs, increased attention should be given to repurposing existing drugs and improving their antimicrobial efficacy, particularly for chronic infections associated with biofilms. Methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) are common causes of biofilm-associated infections however each species has a distinct biofilm phenotype resulting in different biofilm matrix characteristics.. Nanoparticles (NPs) have the potential to significantly enhance the delivery of antimicrobial agents into biofilms, however the physicochemical properties which influence these interactions between NPs and the biofilm are not fully understood. The influence of NP surface chemistry on interactions with MRSA and MSSA biofilms was explored in this study. Mesoporous silica nanoparticles (MSNs) with different surface functionalizations (bare-B, amine-D, carboxyl-C, aromatic-A) were synthesised. Following interaction studies, MSNs were loaded with vancomycin (VAN) to observe biofilm eradication. The two negatively charged MSNs (MSN-B and MSN-C) showed a higher VAN loading in comparison to the positively charged MSNs (MSN-D and MSN-A). Cellular binding with MSN suspensions (0.25 mg mL<sup>-1</sup>) correlated with reduced viability of both MSSA and MRSA biofilm cells. MSNs were shown to be efficient carriers of vancomycin while also displaying significantly improved efficiency compared to free VAN. This allowed the administration of low MSNs concentrations, while maintaining a high local concentration of the antibiotic surrounding the bacterial cells, indicating a promising novel therapeutic approach for S. aureus biofilm infections.</p>

5-Benzylidene-4-Oxazolidinones are Synergistic with Antibiotics for the Treatment of Staphylococcus Aureus Biofilms

2019 ◽  
Author(s):  
Bram Frohock ◽  
Jessica M. Gilbertie ◽  
Jennifer C. Daiker ◽  
Lauren V. Schnabel ◽  
Joshua Pierce
Keyword(s):  
Staphylococcus Aureus ◽  
Human Health ◽  
Matrix Model ◽  
Bacterial Load ◽  
Collagen Matrix ◽  
Resistance Mechanisms ◽  
Novel Therapeutics ◽  
Innovative Treatment ◽  
Antibiotic Action ◽  
Biofilm Infection

<div>The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative treatment approaches to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms and in combination with common antibiotics are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.</div>

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