scholarly journals Antibiofilm Activity of Phorbaketals from the Marine Sponge Phorbas sp. against Staphylococcus aureus

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 301
Author(s):  
Yong-Guy Kim ◽  
Jin-Hyung Lee ◽  
Sangbum Lee ◽  
Young-Kyung Lee ◽  
Buyng Su Hwang ◽  
...  

Biofilm formation by Staphylococcus aureus plays a critical role in the persistence of chronic infections due to its tolerance against antimicrobial agents. Here, we investigated the antibiofilm efficacy of six phorbaketals: phorbaketal A (1), phorbaketal A acetate (2), phorbaketal B (3), phorbaketal B acetate (4), phorbaketal C (5), and phorbaketal C acetate (6), isolated from the Korean marine sponge Phorbas sp. Of these six compounds, 3 and 5 were found to be effective inhibitors of biofilm formation by two S. aureus strains, which included a methicillin-resistant S. aureus. In addition, 3 also inhibited the production of staphyloxanthin, which protects microbes from reactive oxygen species generated by neutrophils and macrophages. Transcriptional analyses showed that 3 and 5 inhibited the expression of the biofilm-related hemolysin gene hla and the nuclease gene nuc1.

2021 ◽  
Author(s):  
Sharmistha Das ◽  
Payel Paul ◽  
Sudipta Chatterjee ◽  
Poulomi Chakraborty ◽  
Ranojit K. Sarker ◽  
...  

Abstract Biofilm, an aggregated form of microbial existence has been a major area of concern in the healthcare units. These sessile microbes not only protect themselves from the host immune system but also exhibit high resistance against several antimicrobials. One such widely reported Gram-positive pathogen is Staphylococcus aureus. This human commensal is known to cause severe harmful diseases like bacteremia, sepsis, pneumonia, etc. Thus, strategies need to be undertaken to deal with such biofilm challenges. In this respect, we aimed to inhibit microbial biofilm formation of Staphylococcus aureus under the influence of a natural compound, piperine. Our study revealed that the higher concentrations of piperine exhibited considerable antimicrobial activity against Staphylococcus aureus. Hence, lower concentrations of piperine were tested to examine its antibiofilm activity. Several experiments like crystal violet (CV) assay, total biofilm protein assay, and fluorescence microscopy observation established that lower concentrations (8 µg/mL and 16 µg/mL) of piperine showed efficient antibiofilm activity against Staphylococcus aureus. It was also noticed that the lower concentrations of piperine did not compromise the microbial growth of Staphylococcus aureus while exhibiting antibiofilm activity. In this connection, we also noticed that the lower concentrations of piperine showed a considerable reduction in microbial metabolic activity. Furthermore, we observed that the compound was found to accumulate reactive oxygen species in the bacterial cells that could play an important role in the inhibition of biofilm formation. Thus, piperine could be considered as a potential antibiofilm agent against the biofilm formation caused by Staphylococcus aureus.


2021 ◽  
Vol 204 (1) ◽  
Author(s):  
Sharmistha Das ◽  
Payel Paul ◽  
Sudipta Chatterjee ◽  
Poulomi Chakraborty ◽  
Ranojit K. Sarker ◽  
...  

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 652 ◽  
Author(s):  
Angela Di Somma ◽  
Antonio Moretta ◽  
Carolina Canè ◽  
Arianna Cirillo ◽  
Angela Duilio

The increasing onset of multidrug-resistant bacteria has propelled microbiology research towards antimicrobial peptides as new possible antibiotics from natural sources. Antimicrobial peptides are short peptides endowed with a broad range of activity against both Gram-positive and Gram-negative bacteria and are less prone to trigger resistance. Besides their activity against planktonic bacteria, many antimicrobial peptides also show antibiofilm activity. Biofilms are ubiquitous in nature, having the ability to adhere to virtually any surface, either biotic or abiotic, including medical devices, causing chronic infections that are difficult to eradicate. The biofilm matrix protects bacteria from hostile environments, thus contributing to the bacterial resistance to antimicrobial agents. Biofilms are very difficult to treat, with options restricted to the use of large doses of antibiotics or the removal of the infected device. Antimicrobial peptides could represent good candidates to develop new antibiofilm drugs as they can act at different stages of biofilm formation, on disparate molecular targets and with various mechanisms of action. These include inhibition of biofilm formation and adhesion, downregulation of quorum sensing factors, and disruption of the pre-formed biofilm. This review focuses on the proprieties of antimicrobial and antibiofilm peptides, with a particular emphasis on their mechanism of action, reporting several examples of peptides that over time have been shown to have activity against biofilm.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hyo-Jung Shin ◽  
Sungtae Yang ◽  
Yong Lim

AbstractStaphylococcus aureus is one of the most common pathogens in biofilm-associated chronic infections. S. aureus living within biofilms evades the host immune response and is more resistant to antibiotics than planktonic bacteria. In this study, we generated S. aureus with low and high levels of biofilm formation using the rbf (regulator of biofilm formation) gene and performed a BioTimer assay to determine the minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of various types of antibiotics. We showed that biofilm formation by S. aureus had a greater effect on MBC than MIC, probably due to the different growth modes between planktonic and biofilm bacteria. Importantly, we found that the MBC for biofilm S. aureus was much higher than that for planktonic cells, but there was little difference in MBC between low and high levels of biofilm formation. These results suggest that once the biofilm is formed, the bactericidal activity of antibiotics is significantly reduced, regardless of the degree of S. aureus biofilm formation. We propose that S. aureus strains with varying degrees of biofilm formation may be useful for evaluating the anti-biofilm activity of antimicrobial agents and understanding antibiotic resistance mechanisms by biofilm development.


2019 ◽  
Author(s):  
Dongzhu Ma ◽  
Jonathan B. Mandell ◽  
Niles P. Donegan ◽  
Ambrose L. Cheung ◽  
Wanyan Ma ◽  
...  

AbstractStaphylococcus aureusis the major organism responsible for surgical implant infections. Antimicrobial treatment of these infections often fails leading to expensive surgical intervention and increased risk of mortality to the patient. The challenge in treating these infections is associated with the high tolerance ofS. aureusbiofilm to antibiotics. MazEF, a toxin-antitoxin system, is thought to be an important regulator of this phenotype, but its physiological function inS. aureusis controversial. Here, we examined the role of MazEF in developing chronic infections by comparing growth and antibiotic tolerance phenotypes in threeS. aureusstrains to their corresponding strains with disruption ofmazFexpression. Strains lackingmazFproduction showed increased biofilm growth, and decreased biofilm antibiotic tolerance. Deletion oficaADBCin themazF::tn background suppressed the growth phenotype observed withmazF-disrupted strains, suggesting the phenotype wasica-dependent. We confirmed these phenotypes in our murine animal model. Loss ofmazFresulted in increased bacterial burden and decreased survival rate compared to its wild-type strain demonstrating that loss of themazFgene caused an increase inS. aureusvirulence. Although lack ofmazFgene expression increasedS. aureusvirulence, it was more susceptible to antibioticsin vivo. Combined, the ability ofmazFto inhibit biofilm formation and promote biofilm antibiotic tolerance plays a critical role in transitioning from an acute to chronic infection that is difficult to eradicate with antibiotics alone.ImportanceSurgical infections are one of the most common types of infections obtained in a hospital.Staphylococcus aureusis the most common pathogen associated with this infection. These infections are resilient and difficult to eradicate as the bacteria form a biofilm, a community of bacteria held together by an extracellular matrix. Compared to bacteria floating in liquid, bacteria in a biofilm are more resistant to antibiotics. The mechanism behind how bacteria develop this resistance and establish a chronic infection is unknown. We demonstrate thatmazEF, a toxin-antitoxin gene, inhibits biofilm formation and promotes biofilm antibiotic tolerance which allowsS. aureusto transition from an acute to chronic infection that cannot be eradicated with antibiotics but is less virulent. This gene not only makes the bacteria more tolerant to antibiotics but makes the bacteria more tolerant to the host.


mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Dongzhu Ma ◽  
Jonathan B. Mandell ◽  
Niles P. Donegan ◽  
Ambrose L. Cheung ◽  
Wanyan Ma ◽  
...  

ABSTRACT Staphylococcus aureus is the major organism responsible for surgical implant infections. Antimicrobial treatment of these infections often fails, leading to expensive surgical intervention and increased risk of mortality to the patient. The challenge in treating these infections is associated with the high tolerance of S. aureus biofilm to antibiotics. MazEF, a toxin-antitoxin system, is thought to be an important regulator of this phenotype, but its physiological function in S. aureus is controversial. Here, we examined the role of MazEF in developing chronic infections by comparing growth and antibiotic tolerance phenotypes in three S. aureus strains to their corresponding strains with disruption of mazF expression. Strains lacking mazF production showed increased biofilm growth and decreased biofilm antibiotic tolerance. Deletion of icaADBC in the mazF::Tn background suppressed the growth phenotype observed with mazF-disrupted strains, suggesting the phenotype was ica dependent. We confirmed these phenotypes in our murine animal model. Loss of mazF resulted in increased bacterial burden and decreased survival rate of mice compared to its wild-type strain demonstrating that loss of the mazF gene caused an increase in S. aureus virulence. Although lack of mazF gene expression increased S. aureus virulence, it was more susceptible to antibiotics in vivo. Combined, the ability of mazF to inhibit biofilm formation and promote biofilm antibiotic tolerance plays a critical role in transitioning from an acute to chronic infection that is difficult to eradicate with antibiotics alone. IMPORTANCE Surgical infections are one of the most common types of infections encountered in a hospital. Staphylococcus aureus is the most common pathogen associated with this infection. These infections are resilient and difficult to eradicate, as the bacteria form biofilm, a community of bacteria held together by an extracellular matrix. Compared to bacteria that are planktonic, bacteria in a biofilm are more resistant to antibiotics. The mechanism behind how bacteria develop this resistance and establish a chronic infection is unknown. We demonstrate that mazEF, a toxin-antitoxin gene, inhibits biofilm formation and promotes biofilm antibiotic tolerance which allows S. aureus to transition from an acute to chronic infection that cannot be eradicated with antibiotics but is less virulent. This gene not only makes the bacteria more tolerant to antibiotics but makes the bacteria more tolerant to the host.


2019 ◽  
Vol 86 (5) ◽  
Author(s):  
Thaís Glatthardt ◽  
Juliana Curityba de Mello Campos ◽  
Raiane Cardoso Chamon ◽  
Thiago Freitas de Sá Coimbra ◽  
Giulia de Almeida Rocha ◽  
...  

ABSTRACT The microbiota influences host health through several mechanisms, including protecting it from pathogen colonization. Staphylococcus epidermidis is one of the most frequently found species in the skin microbiota, and its presence can limit the development of pathogens such as Staphylococcus aureus. S. aureus causes diverse types of infections ranging from skin abscesses to bloodstream infections. Given the increasing prevalence of S. aureus drug-resistant strains, it is imperative to search for new strategies for treatment and prevention. Thus, we investigated the activity of molecules produced by a commensal S. epidermidis isolate against S. aureus biofilms. We showed that molecules present in S. epidermidis cell-free conditioned media (CFCM) caused a significant reduction in biofilm formation in most S. aureus clinical isolates, including all 4 agr types and agr-defective strains, without any impact on growth. S. epidermidis molecules also disrupted established S. aureus biofilms and reduced the antibiotic concentration required to eliminate them. Preliminary characterization of the active compound showed that its activity is resistant to heat, protease inhibitors, trypsin, proteinase K, and sodium periodate treatments, suggesting that it is not proteinaceous. RNA sequencing revealed that S. epidermidis-secreted molecules modulate the expression of hundreds of S. aureus genes, some of which are associated with biofilm production. Biofilm formation is one of the main virulence factors of S. aureus and has been associated with chronic infections and antimicrobial resistance. Therefore, molecules that can counteract this virulence factor may be promising alternatives as novel therapeutic agents to control S. aureus infections. IMPORTANCE S. aureus is a leading agent of infections worldwide, and its main virulence characteristic is the ability to produce biofilms on surfaces such as medical devices. Biofilms are known to confer increased resistance to antimicrobials and to the host immune responses, requiring aggressive antibiotic treatment and removal of the infected surface. Here, we investigated a new source of antibiofilm compounds, the skin microbiome. Specifically, we found that a commensal strain of S. epidermidis produces molecules with antibiofilm activity, leading to a significant decrease of S. aureus biofilm formation and to a reduction of previously established biofilms. The molecules potentiated the activity of antibiotics and affected the expression of hundreds of S. aureus genes, including those associated with biofilm formation. Our research highlights the search for compounds that can aid us in the fight against S. aureus infections.


2018 ◽  
Vol 18 (1) ◽  
pp. 42-55
Author(s):  
Annisa Fitria

Chronical wound often caused by bacteria which has antibiotic resistance characteristic and presence of biofilm formation. This study aims to evaluate the bactericidal and antibiofilm activity of stem bark of Jatropha multifida L. against Staphylococcus aureus and MRSA (Methicillin-Resistant Staphylococcus aureus), as alternative antimicrobial agents. Examination of bactericidal activity of the extract was performed by time-kill assay to determine the speed of the extract to eradicate bacteria. The inhibitory activity of extract toward biofilm production was quantified using spectrophotometric method. The extract showed bactericidal activity which can be achieved at 8 hours and 12 hours against Staphylococcus aureus and MRSA in MBC value of 0.5 mg/mL and 1 mg/mL. The extract exhibited antibiofilm activity which indicates by its IC50 value of 0.3 mg/mL and 0.76 mg/mL against Staphylococcus aureus and MRSA. These experiments have shown the potential of the extract of  Jatropha multifida L. stem bark as a bioactive substance in a topical agent for chronical skin infection.  


2018 ◽  
pp. 93-100
Author(s):  
D. M. Dudikova ◽  
Z. S. Suvorova ◽  
V. V. Nedashkivska ◽  
A. O. Sharova ◽  
M. L. Dronova ◽  
...  

Bacterial biofilm, particularly formed by Pseudomonas aeruginosa, are a cause of severe chronic infectious diseases. Bacteria within a biofilm are phenotypically more resistant to antibiotics and the macroorganism immune system, making it an important virulence factor for many microbes. The aminopropanol derivatives with adamantyl (KVM-97) and N-alkylaryl radicals (KVM-194, KVM-204, KVM-261, and KVM-262) were used as study object. The aim of this study was to investigate the antibiofilm activity of compounds on biofilm formation and on mature biofilm of P. aeruginosa. The effects of the aminopropanol derivatives on the biofilm mass were evaluated by using crystal violet assay. Ciprofloxacin, meropenem, ceftazidime, gentamicin were used as reference substances. Reported results demonstrate that all compounds displayed antibiofilm activity at the tested concentrations. Remarkable reduction in biofilm formation of P. aeruginosa was found after treatment with KVM-97, KVM-261 and KVM-262 in high concentration (5× MIC), biofilm inhibition activity were 84.3%, 90.5% and 83.3% respectively. After a treatment with KVM-204 at 250 μg/ml (5× MIC) 76.6% of the preformed 24-hr biofilms were destroyed. Furthermore, compounds KVM-97, KVM-194, and KVM-261 in both concentrations showed potent antibiofilm activity against the P. aeruginosa, inhibition activity values being between 56.7 and 65.7%. All tested compounds in dose-dependent manner exhibited pronounced inhibition activity against mature 5-days P. аeruginosa biofilm. It was also observed that tested compounds show high antibiofilm activity in comparison to reference antimicrobials. The aminopropanol derivatives may provide templates for a new group of antimicrobial agents and potential future therapeutics for treating chronic infections.


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