scholarly journals Detection of Quorum-Sensing Molecules for Pathogenic Molecules Using Cell-Based and Cell-Free Biosensors

Antibiotics ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 259 ◽  
Author(s):  
Craig Miller ◽  
Jordon Gilmore
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Genetic Material ◽  
Treatment Strategies ◽  
Signaling Molecules ◽  
Resistant Bacteria ◽  
Acute Infections

Since the discovery and subsequent use of penicillin, antibiotics have been used to treat most bacterial infections in the U.S. Over time, the repeated prescription of many antibiotics has given rise to many antibiotic-resistant microbes. A bacterial strain becomes resistant by horizontal gene transfer, where surviving microbes acquire genetic material or DNA fragments from adjacent bacteria that encode for resistance. In order to avoid significant bacterial resistance, novel and target therapeutics are needed. Further advancement of diagnostic technologies could be used to develop novel treatment strategies. The use of biosensors to detect quorum-sensing signaling molecules has the potential to provide timely diagnostic information toward mitigating the multidrug-resistant bacteria epidemic. Resistance and pathogenesis are controlled by quorum-sensing (QS) circuits. QS systems secrete or passively release signaling molecules when the bacterial concentration reaches a certain threshold. Signaling molecules give an early indication of virulence. Detection of these compounds in vitro or in vivo can be used to identify the onset of infection. Whole-cell and cell-free biosensors have been developed to detect quorum-sensing signaling molecules. This review will give an overview of quorum networks in the most common pathogens found in chronic and acute infections. Additionally, the current state of research surrounding the detection of quorum-sensing molecules will be reviewed. Followed by a discussion of future works toward the advancement of technologies to quantify quorum signaling molecules in chronic and acute infections.

scholarly journals Multiple Mechanisms of the Synthesized Antimicrobial Peptide TS against Gram-Negative Bacteria for High Efficacy Antibacterial Action In Vivo

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 60
Author(s):  
Rui Zhang ◽  
Xiaobo Fan ◽  
Xinglu Jiang ◽  
Mingyuan Zou ◽  
Han Xiao ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Divalent Cations ◽  
Resistant Bacteria ◽  
Antibacterial Drug ◽  
Gram Negative Bacteria ◽  
Gram Negative

The emergence of drug-resistant bacteria emphasizes the urgent need for novel antibiotics. The antimicrobial peptide TS shows extensive antibacterial activity in vitro and in vivo, especially in gram-negative bacteria; however, its antibacterial mechanism is unclear. Here, we find that TS without hemolytic activity disrupts the integrity of the outer bacterial cell membrane by displacing divalent cations and competitively binding lipopolysaccharides. In addition, the antimicrobial peptide TS can inhibit and kill E. coli by disintegrating the bacteria from within by interacting with bacterial DNA. Thus, antimicrobial peptide TS’s multiple antibacterial mechanisms may not easily induce bacterial resistance, suggesting use as an antibacterial drug to be for combating bacterial infections in the future.

scholarly journals Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo, and Clinical Application

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1497
Author(s):  
Katarzyna M. Danis-Wlodarczyk ◽  
Daniel J. Wozniak ◽  
Stephen T. Abedon
Keyword(s):  
Bacterial Infections ◽  
Bacterial Resistance ◽  
High Efficiency ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
Drug Classes ◽  
Peptidoglycan Hydrolases ◽  
Bacterial Peptidoglycan

Over the past few decades, we have witnessed a surge around the world in the emergence of antibiotic-resistant bacteria. This global health threat arose mainly due to the overuse and misuse of antibiotics as well as a relative lack of new drug classes in development pipelines. Innovative antibacterial therapeutics and strategies are, therefore, in grave need. For the last twenty years, antimicrobial enzymes encoded by bacteriophages, viruses that can lyse and kill bacteria, have gained tremendous interest. There are two classes of these phage-derived enzymes, referred to also as enzybiotics: peptidoglycan hydrolases (lysins), which degrade the bacterial peptidoglycan layer, and polysaccharide depolymerases, which target extracellular or surface polysaccharides, i.e., bacterial capsules, slime layers, biofilm matrix, or lipopolysaccharides. Their features include distinctive modes of action, high efficiency, pathogen specificity, diversity in structure and activity, low possibility of bacterial resistance development, and no observed cross-resistance with currently used antibiotics. Additionally, and unlike antibiotics, enzybiotics can target metabolically inactive persister cells. These phage-derived enzymes have been tested in various animal models to combat both Gram-positive and Gram-negative bacteria, and in recent years peptidoglycan hydrolases have entered clinical trials. Here, we review the testing and clinical use of these enzymes.

scholarly journals Ajoene, a Sulfur-Rich Molecule from Garlic, Inhibits Genes Controlled by Quorum Sensing

2012 ◽  
Vol 56 (5) ◽  
pp. 2314-2325 ◽  
Author(s):  
Tim Holm Jakobsen ◽  
Maria van Gennip ◽  
Richard Kerry Phipps ◽  
Meenakshi Sundaram Shanmugham ◽  
Louise Dahl Christensen ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Treatment Strategies ◽  
Significant Inhibition ◽  
Control Group ◽  
Content Type ◽  
Multiresistant Bacteria

ABSTRACTIn relation to emerging multiresistant bacteria, development of antimicrobials and new treatment strategies of infections should be expected to become a high-priority research area. Quorum sensing (QS), a communication system used by pathogenic bacteria likePseudomonas aeruginosato synchronize the expression of specific genes involved in pathogenicity, is a possible drug target. Previousin vitroandin vivostudies revealed a significant inhibition ofP. aeruginosaQS by crude garlic extract. By bioassay-guided fractionation of garlic extracts, we determined the primary QS inhibitor present in garlic to be ajoene, a sulfur-containing compound with potential as an antipathogenic drug. By comprehensivein vitroandin vivostudies, the effect of synthetic ajoene towardP. aeruginosawas elucidated. DNA microarray studies of ajoene-treatedP. aeruginosacultures revealed a concentration-dependent attenuation of a few but central QS-controlled virulence factors, including rhamnolipid. Furthermore, ajoene treatment ofin vitrobiofilms demonstrated a clear synergistic, antimicrobial effect with tobramycin on biofilm killing and a cease in lytic necrosis of polymorphonuclear leukocytes. Furthermore, in a mouse model of pulmonary infection, a significant clearing of infectingP. aeruginosawas detected in ajoene-treated mice compared to a nontreated control group. This study adds to the list of examples demonstrating the potential of QS-interfering compounds in the treatment of bacterial infections.

scholarly journals Tackling Virulence of Pseudomonas aeruginosa by the Natural Furanone Sotolon

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 871
Author(s):  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
Ahmed Al Saqr ◽  
Ahmed Alalaiwe ◽  
Hisham A. Abbas ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Therapeutic Agent ◽  
Bacterial Resistance ◽  
Inhibitory Concentration ◽  
Bacterial Biofilm ◽  
Resistant Bacteria ◽  
Resistance Development

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics.

scholarly journals A Review of the Combination Therapy of Low Frequency Ultrasound with Antibiotics

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Yun Cai ◽  
Jin Wang ◽  
Xu Liu ◽  
Rui Wang ◽  
Lei Xia
Keyword(s):  
Combination Therapy ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Low Frequency ◽  
Bactericidal Effect ◽  
Low Frequency Ultrasound ◽  
Biofilm Bacteria ◽  
Frequency Ultrasound

Single antimicrobial therapy has been unable to resist the global spread of bacterial resistance. Literatures of availablein vitroandin vivostudies were reviewed and the results showed that low frequency ultrasound (LFU) has a promising synergistic bactericidal effect with antibiotics against both planktonic and biofilm bacteria. It also can facilitate the release of antibiotics from medical implants. As a noninvasive and targeted therapy, LFU has great potential in treating bacterial infections. However, more in-depth and detailed studies are still needed before LFU is officially applied as a combination therapy in the field of anti-infective treatment.

In Vitro and In Vivo Efficacy of Catheters Impregnated With Antiseptics or Antibiotics: Evaluation of the Risk of Bacterial Resistance to the Antimicrobials in the Catheters

2001 ◽  
Vol 22 (10) ◽  
pp. 640-646 ◽  
Author(s):  
Lester A. Sampath ◽  
Suhas M. Tambe ◽  
Shanta M. Modak
Keyword(s):  
Bacterial Resistance ◽  
Test Organism ◽  
Similar Efficacy ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
In Vivo Efficacy ◽  
Development Of Resistance ◽  
Zones Of Inhibition

AbstractObjective:To compare the efficacy of a new antiseptic catheter containing silver sulfadiazine and chlorhexidine on the external surface and chlorhexidine in the lumens to an antibiotic catheter impregnated with minocycline and rifampin on its external and luminal surfaces.Design:Experimental trial.Methods:Antimicrobial spectrum of catheters was determined by zones of inhibition. Resistance to luminal colonization was tested in vitro by locking catheter lumens withStaphylococcus epidermidisorStaphylococcus aureusculture after 7 days of perfusion. In vitro development of resistance to the antiseptic or antibiotic combination used in catheters was investigated. In vivo efficacy was tested (rat subcutaneous model) by challenge with sensitive or antibiotic-resistant bacteria.Results:Antiseptic and antibiotic catheters exhibited broad-spectrum action. However, antibiotic catheters were not effective againstCandidaspecies andPseudomonas aeruginosa.Both catheters prevented luminal colonization. Compared to controls, both test catheters resisted colonization when challenged withS aureus7 and 14 days' postimplant (P<.05).Repeated in vitro exposure ofS epidermidisculture to the antibiotic and antiseptic combinations led to small increases in the minimum inhibitory concentration (15 times and 2 times, respectively). Unlike the antibiotic catheter, the in vitro and in vivo activity of the antiseptic catheter was unaffected by the resistance profile of the test organism. Antiseptic catheters were more effective than antibiotic catheters in preventing colonization by rifampin-resistantS epidermidisin vivo (P<.05).Conclusions:Antiseptic and antibiotic catheters exhibit similar efficacy; however, when challenged with a rifampin-resistant strain, the antibiotic catheter appeared to be more susceptible to colonization than the antiseptic device.

scholarly journals Antibacterial Efficacy of Temperate Phage-Mediated Inhibition of Bacterial Group Motilities

2012 ◽  
Vol 56 (11) ◽  
pp. 5612-5617 ◽  
Author(s):  
In-Young Chung ◽  
Nuri Sim ◽  
You-Hee Cho
Keyword(s):  
Bacterial Infections ◽  
Systemic Infection ◽  
Temperate Phage ◽  
Twitching Motility ◽  
Bacterial Group ◽  
Swarming Motility ◽  
Content Type ◽  
Acute Infections

ABSTRACTPhage therapy against bacterial pathogens has been resurrected as an alternative and supplementary anti-infective modality. Here, we observed that bacterial group motilities were impaired inPseudomonas aeruginosastrain PA14 lysogens for some temperate siphophages; the PA14 lysogens for DMS3 and MP22 were impaired in swarming motility, whereas the PA14 lysogen for D3112 was impaired in twitching motility. The swarming and twitching motilities of PA14 were also affected in the presence of MP22 and D3112, respectively. Thein vitrokilling activities of D3112 and MP22 toward PA14 did not differ, and neither did theirin vivopersistence in the absence of bacterial infections in mice as well as in flies. Nevertheless, administration of D3112, not MP22, significantly reduced the mortality and the bacterial burdens in murine peritonitis-sepsis andDrosophilasystemic infection caused by PA14. Taken together, we suggest that a temperate phage-mediated twitching motility inhibition might be comparably effective to control the acute infections caused byP. aeruginosa.

scholarly journals Effective antibacterial and anti-hemolysin activity of ellipticine hydrochloride against Streptococcus suis in mouse model

2021 ◽  
Author(s):  
Chenchen Wang ◽  
Hao Lu ◽  
Manli Liu ◽  
Gaoyan Wang ◽  
Xiaodan Li ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Hemolytic Activity ◽  
Bacterial Resistance ◽  
Bacterial Load ◽  
Streptococcus Suis ◽  
Resistant Bacteria ◽  
Inappropriate Use ◽  
Important Virulence Factor

Streptococcal toxic shock-like syndrome (STSLS) caused by the epidemic strain of Streptococcus suis leads to severe inflammation and high mortality. The life and health of humans and animals are also threatened by the increasingly severe antimicrobial resistance in Streptococcus suis (S. suis). To discover novel strategies for the treatment of S. suis is an urgent need. Suilysin (SLY) is considered to be an important virulence factor in the pathogenesis of S. suis. In this study, ellipticine hydrochloride (EH) was firstly reported as a compound to antagonize the hemolytic activity of SLY. In vitro, EH was found to effectively inhibit SLY-mediated hemolytic activity. Furthermore, EH and SLY had a strong affinity, thereby directly binding to SLY to interfere the hemolytic activity. Meanwhile, it was worth noting that EH was also found to have a significant antibacterial activity. In vivo, compared with traditional ampicillin, EH could not only significantly improve the survival rate of mice infected with S. suis 2 strain Sc19, but also relieve lung pathological damage. Furthermore, EH effectively decreased the levels of inflammatory cytokines (IL-6, TNF-α) and blood biochemistry (ALT, AST, CK) in Sc19-infected mice. Additionally, EH markedly reduced the bacterial load of tissues in Sc19-infected mice. In conclusion, our findings suggest that EH can be a potential compound for treating S. suis infection in view of its antibacterial and anti-hemolysin activity. Importance In recent years, the inappropriate use of antibiotics unnecessarily causes the continuous emergence of resistant bacteria. The antimicrobial resistance of Streptococcus suis (S. suis) becomes also an increasingly serious problem. Targeting virulence can reduce the selective pressure of bacteria on antibiotics, thereby alleviating the development of bacterial resistance to a certain extent. Meanwhile, the excessive inflammatory response caused by S. suis infection is considered the primary cause of acute death. Here, we found that ellipticine hydrochloride (EH) exhibited effective antibacterial and anti-hemolysin activity against S. suis in vitro. In vivo, compared with ampicillin, EH had a significant protective effect on S. suis 2 strain Sc19-infected mice. Our results indicated that EH with dual antibacterial and antivirulence effects will contribute to medicating S. suis infections and alleviating the antimicrobial resistance of S. suis to a certain extent. More importantly, EH may develop into a promising drug for the treatment of acute death caused by excessive inflammation.

scholarly journals Antimicrobial applications of nanoliposome encapsulated silver nanoparticles: a potential strategy to overcome bacterial resistance

2020 ◽  
Vol 16 ◽  
Author(s):  
M.R. Mozafari ◽  
Sarabanou Torkaman ◽  
Fatemeh Mahsa Karamouzian ◽  
Babak Rasti ◽  
Bikash Baral
Keyword(s):  
Silver Nanoparticles ◽  
Bacterial Infections ◽  
Bacterial Resistance ◽  
Water Soluble ◽  
Severe Illness ◽  
Efficient System ◽  
Antimicrobial Substances ◽  
Potential Strategy

: Bacterial infections result in hundreds of million cases of severe illness annually worldwide. Rapidly increasing drug resistance of pathogens further aggravates this threat to human health and warrants the search for effective broadspectrum antibacterial agents. Silver metal has a long history of application in human medicine and healthcare. In ancient times, silver was employed as a disinfectant for water purification and storage while it is still being used as an antimicrobial ingredient in some nanotechnology-based products. Encapsulation of antimicrobial substances such as silver nanoparticles in nanoliposomes could provide protection and targeting for the encapsulated or entrapped material. Nanoliposomes are biocompatible and biodegradable drug delivery systems with the ability to encapsulate both lipidsoluble and water-soluble compounds, as well as metal ions. Furthermore, nanoliposomes have been shown to be able to deliver encapsulated agents to target bacteria in vitro as well as in vivo. In this review, we present the use of nanoliposome-encapsulated silver nanoparticles as an efficient system for antibacterial applications.

Functional Nanomaterials for the Detection and Control of Bacterial Infections

2019 ◽  
Vol 19 (27) ◽  
pp. 2449-2475 ◽  
Author(s):  
Huiqiong Jia ◽  
Mohamed S. Draz ◽  
Zhi Ruan
Keyword(s):  
Bacterial Infections ◽  
Chemical Properties ◽  
Multidrug Resistant ◽  
Optimal Time ◽  
Resistant Bacteria ◽  
Functional Nanomaterials ◽  
Detection Techniques ◽  
Physical And Chemical

Infections with multidrug-resistant bacteria that are difficult to treat with commonly used antibiotics have spread globally, raising serious public health concerns. Conventional bacterial detection techniques are time-consuming, which may delay treatment for critically ill patients past the optimal time. There is an urgent need for rapid and sensitive diagnosis and effective treatments for multidrug-resistant pathogenic bacterial infections. Advances in nanotechnology have made it possible to design and build nanomaterials with therapeutic and diagnostic capabilities. Functional nanomaterials that can specifically interact with bacteria offer additional options for the diagnosis and treatment of infections due to their unique physical and chemical properties. Here, we summarize the recent advances related to the preparation of nanomaterials and their applications for the detection and treatment of bacterial infection. We pay particular attention to the toxicity of therapeutic nanoparticles based on both in vitro and in vivo assays. In addition, the major challenges that require further research and future perspectives are briefly discussed.

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