scholarly journals Enhanced Resistance to Bacterial Infection in Protegrin-1 Transgenic Mice

2008 ◽  
Vol 52 (5) ◽  
pp. 1812-1819 ◽  
Author(s):  
Queenie C. K. Cheung ◽  
Patricia V. Turner ◽  
Cheng Song ◽  
De Wu ◽  
Hugh Y. Cai ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Bacterial Infection ◽  
Ectopic Expression ◽  
Farm Animals ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Cell Counts ◽  
Enhanced Resistance ◽  
Wide Range

ABSTRACT Antibiotic-resistant bacteria have become a public health concern. It was suggested that one source of resistant pathogens may be food-producing animals. Alternative approaches are therefore needed to enhance the resistance of farm animals to bacterial infection. Protegrin-1 (PG-1) is a neutrophil-derived antimicrobial peptide that possesses activity against a wide range of bacteria and enveloped viruses. Here we report on the production of transgenic mice that ectopically expressed PG-1 and compare their susceptibilities to Actinobacillus suis infection with those of their wild-type (WT) littermates. Of the 126 mice that were challenged with A. suis, 87% of the transgenic mice survived, whereas 31% of their WT littermates survived. The PG-1 transgenic mice had significantly lower bacterial loads in their lungs and reduced numbers of pulmonary pathological lesions. The antimicrobial function of PG-1 was confirmed in vitro by using fibroblast cells isolated from the transgenic mice but not the WT mice. Moreover, differential blood cell counts in bronchoalveolar lavage fluid indicated greater number of neutrophils in PG-1 transgenic mice than in their WT littermates after bacterial challenge. Our data suggest that the ectopic expression of PG-1 in mice confers enhanced resistance to bacterial infection, laying the foundation for the development of livestock with improved resistance to infection.

scholarly journals A Machine Learning Tool to Predict the Antibacterial Capacity of Nanoparticles

Nanomaterials ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1774
Author(s):  
Mahsa Mirzaei ◽  
Irini Furxhi ◽  
Finbarr Murphy ◽  
Martin Mullins
Keyword(s):  
Machine Learning ◽  
Performance Metrics ◽  
Exposure Dose ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Attribute Importance ◽  
Experimental Conditions ◽  
Wide Range ◽  
Antibacterial Capacity

The emergence and rapid spread of multidrug-resistant bacteria strains are a public health concern. This emergence is caused by the overuse and misuse of antibiotics leading to the evolution of antibiotic-resistant strains. Nanoparticles (NPs) are objects with all three external dimensions in the nanoscale that varies from 1 to 100 nm. Research on NPs with enhanced antimicrobial activity as alternatives to antibiotics has grown due to the increased incidence of nosocomial and community acquired infections caused by pathogens. Machine learning (ML) tools have been used in the field of nanoinformatics with promising results. As a consequence of evident achievements on a wide range of predictive tasks, ML techniques are attracting significant interest across a variety of stakeholders. In this article, we present an ML tool that successfully predicts the antibacterial capacity of NPs while the model’s validation demonstrates encouraging results (R2 = 0.78). The data were compiled after a literature review of 60 articles and consist of key physico-chemical (p-chem) properties and experimental conditions (exposure variables and bacterial clustering) from in vitro studies. Following data homogenization and pre-processing, we trained various regression algorithms and we validated them using diverse performance metrics. Finally, an important attribute evaluation, which ranks the attributes that are most important in predicting the outcome, was performed. The attribute importance revealed that NP core size, the exposure dose, and the species of bacterium are key variables in predicting the antibacterial effect of NPs. This tool assists various stakeholders and scientists in predicting the antibacterial effects of NPs based on their p-chem properties and diverse exposure settings. This concept also aids the safe-by-design paradigm by incorporating functionality tools.

scholarly journals Caerin 1.1 and 1.9 peptides from Australian tree frog inhibit antibiotic-resistant bacteria growth in a murine skin infection model

2021 ◽  
Author(s):  
Shu Chen ◽  
Pingping Zhang ◽  
Liyin Xiao ◽  
Ying Liu ◽  
Kuihai Wu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infection ◽  
Bacterial Resistance ◽  
Resistant Bacteria ◽  
Infection Model ◽  
Temperature Sensitive ◽  
Tree Frog ◽  
Bacteria Growth ◽  
Wide Range

AbstractHost-defence caerin 1.9 peptide was originally isolated from skin secretion of Australian tree frog, and inhibits the growth of a wide range of bacteria in vitro. In this study, we demonstrated that caerin 1.9 shows high bioactivity against several bacteria strains, such as Staphylococcus aureus, Acinetobacter Baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus hemolyiicus in vitro. Importantly, unlike antibiotic Tazocin, caerin 1.9 does not induce bacterial resistance after 30 rounds of in vitro culture. Moreover, caerin 1.1, another peptide of caerin family, has additive antibacterial effect when used together with caerin 1.9. Furthermore, caerin 1.1 and 1.9 prepared in the form of a temperature sensitive gel inhibit MRSA growth in skin bacterial infection model of two murine strains. These results indicate that caerin 1.1 and 1.9 may have the advantage than conventional antibiotics against bacterial infection of skin.

scholarly journals In Vitro Synergistic Interactions of Isavuconazole and Echinocandins against Candida auris

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 355
Author(s):  
Unai Caballero ◽  
Sarah Kim ◽  
Elena Eraso ◽  
Guillermo Quindós ◽  
Valvanera Vozmediano ◽  
...  
Keyword(s):  
Interaction Model ◽  
Antifungal Drugs ◽  
Health Concern ◽  
Candida Auris ◽  
Fungistatic Activity ◽  
Drug Concentrations ◽  
Low Concentrations ◽  
Wide Range ◽  
Time Kill

Candida auris is an emergent fungal pathogen that causes severe infectious outbreaks globally. The public health concern when dealing with this pathogen is mainly due to reduced susceptibility to current antifungal drugs. A valuable alternative to overcome this problem is to investigate the efficacy of combination therapy. The aim of this study was to determine the in vitro interactions of isavuconazole with echinocandins against C. auris. Interactions were determined using a checkerboard method, and absorbance data were analyzed with different approaches: the fractional inhibitory concentration index (FICI), Greco universal response surface approach, and Bliss interaction model. All models were in accordance and showed that combinations of isavuconazole with echinocandins resulted in an overall synergistic interaction. A wide range of concentrations within the therapeutic range were selected to perform time-kill curves. These confirmed that isavuconazole–echinocandin combinations were more effective than monotherapy regimens. Synergism and fungistatic activity were achieved with combinations that included isavuconazole in low concentrations (≥0.125 mg/L) and ≥1 mg/L of echinocandin. Time-kill curves revealed that once synergy was achieved, combinations of higher drug concentrations did not improve the antifungal activity. This work launches promising results regarding the combination of isavuconazole with echinocandins for the treatment of C. auris infections.

scholarly journals A Putative Cro-Like Repressor Contributes to Arylomycin Resistance in Staphylococcus aureus

2015 ◽  
Vol 59 (6) ◽  
pp. 3066-3074 ◽  
Author(s):  
Arryn Craney ◽  
Floyd E. Romesberg
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Transcriptional Regulator ◽  
Signal Peptidase ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Type I ◽  
Wall Teichoic Acid ◽  
Content Type ◽  
Wide Range

ABSTRACTAntibiotic-resistant bacteria are a significant public health concern and motivate efforts to develop new classes of antibiotics. One such class of antibiotics is the arylomycins, which target type I signal peptidase (SPase), the enzyme responsible for the release of secreted proteins from their N-terminal leader sequences. Despite the essentiality, conservation, and relative accessibility of SPase, the activity of the arylomycins is limited against some bacteria, including the important human pathogenStaphylococcus aureus. To understand the origins of the limited activity againstS. aureus, we characterized the susceptibility of a panel of strains to two arylomycin derivatives, arylomycin A-C16and its more potent analog arylomycin M131. We observed a wide range of susceptibilities to the two arylomycins and found that resistant strains were sensitized by cotreatment with tunicamycin, which inhibits the first step of wall teichoic acid synthesis. To further understand howS. aureusresponds to the arylomycins, we profiled the transcriptional response ofS. aureusNCTC 8325 to growth-inhibitory concentrations of arylomycin M131 and found that it upregulates the cell wall stress stimulon (CWSS) and an operon consisting of a putative transcriptional regulator and three hypothetical proteins. Interestingly, we found that mutations in the putative transcriptional regulator are correlated with resistance, and selection for resistanceex vivodemonstrated that mutations in this gene are sufficient for resistance. The results begin to elucidate howS. aureuscopes with secretion stress and how it evolves resistance to the inhibition of SPase.

scholarly journals Bcl-2 antagonist apogossypol (NSC736630) displays single-agent activity in Bcl-2–transgenic mice and has superior efficacy with less toxicity compared with gossypol (NSC19048)

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 3211-3219 ◽  
Author(s):  
Shinichi Kitada ◽  
Christina L. Kress ◽  
Maryla Krajewska ◽  
Lee Jia ◽  
Maurizio Pellecchia ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Parent Compound ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Low Grade ◽  
Altered Expression ◽  
Cell Counts

Abstract Altered expression of Bcl-2 family proteins plays central roles in apoptosis dysregulation in cancer and leukemia, promoting malignant cell expansion and contributing to chemoresistance. In this study, we compared the toxicity and efficacy in mice of natural product gossypol and its semisynthetic derivative apo-gossypol, compounds that bind and inhibit antiapoptotic Bcl-2 family proteins. Daily oral dosing studies showed that mice tolerate doses of apogossypol 2- to 4-times higher than gossypol. Hepatotoxicity and gastrointestinal toxicity represented the major adverse activities of gossypol, with apogossypol far less toxic. Efficacy was tested in transgenic mice in which Bcl-2 is overexpressed in B cells, resembling low-grade follicular lymphoma in humans. In vitro, Bcl-2–expressing B cells from transgenic mice were more sensitive to cytotoxicity induced by apogossypol than gossypol, with LD50 values of 3 to 5 μM and 7.5 to 10 μM, respectively. In vivo, using the maximum tolerated dose of gossypol for sequential daily dosing, apogossypol displayed superior activity to gossypol in terms of reducing splenomegaly and reducing B-cell counts in spleens of Bcl-2–transgenic mice. Taken together, these studies indicate that apogossypol is superior to parent compound gossypol with respect to toxicology and efficacy, suggesting that further development of this compound for cancer therapy is warranted.

scholarly journals In vitro Insecticidal and Time-Kill Profile of Ethyl Acetate Extract of Marine Streptomyces sp. Isolated from Sundarbans, Bangladesh

2015 ◽  
Vol 17 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Md Anwarul Haque ◽  
Ashish Kumar Sarker ◽  
Mohammad Sayful Islam ◽  
Md Ajijur Rahman ◽  
Md Akter Uzzaman Chouduri ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Mangrove Forest ◽  
Bacterial Strains ◽  
Streptomyces Species ◽  
Streptomyces Sp ◽  
Cell Counts ◽  
Wide Range ◽  
Marine Streptomyces ◽  
Time Kill

The marine soil and sediment samples were collected from different locations of mangrove forest Sundarbans, Bangladesh the largest tidal halophytic mangrove forest in the world. A total of twenty nine Actinomycete strains (AIAH-1 to AIAH-29) were isolated by serial dilution method using isolation media. Among twenty nine strains, AIAH-10 was selected for further study due to its potent antibacterial activity against a wide range of pathogenic bacterial strains. On the basis of morphological, cultural and biochemical studies, the strain AIAH-10 was assigned to Streptomyces sp. The present study was designed to investigate the in vitro insecticidal and time-kill profile of ethyl acetate extracts of marine Streptomyces sp. A dose dependent mortality was observed against the larvae of Sitophilus oryzae. The larval mortality was recorded as 100% in the concentration of 80 mg/ml and higher concentrations, LC50 was found as 11.48 mg/ml. The minimum inhibitory concentration was recorded as 8 to 32 mg/ml against six different pathogenic bacterial strains. Average Log10 reductions in viable cell counts for the extracts ranged from 1.91 Log10 and 2.86 Log10 cfu/mL after 3 h interaction and 2.10 Log10 and 2.93 Log10 after 6 h interaction at MIC, 2 × MIC, 3 × MIC and 4 × MIC concentrations. This investigation reveals that the Streptomyces species isolated from Sundarbans, Bangladesh may be interesting source for the isolation of potent bioactive compounds. DOI: http://dx.doi.org/10.3329/bpj.v17i2.22332 Bangladesh Pharmaceutical Journal 17(2): 151-156, 2014

scholarly journals Synthesis, In Silico, and In Vitro Evaluation of Long Chain Alkyl Amides from 2-Amino-4-Quinolone Derivatives as Biofilm Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 327 ◽  
Author(s):  
Mariana Espinosa-Valdés ◽  
Sara Borbolla-Alvarez ◽  
Ana Delgado-Espinosa ◽  
Juan Sánchez-Tejeda ◽  
Anabelle Cerón-Nava ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Biofilm Formation ◽  
Active Sites ◽  
Multidrug Resistant ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Biofilm Inhibition ◽  
Amide Derivatives ◽  
Long Chain

Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N-acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa. All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins.

scholarly journals The Pomegranate: Effects on Bacteria and Viruses That Influence Human Health

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Amy B. Howell ◽  
Doris H. D'Souza
Keyword(s):  
Antimicrobial Activity ◽  
Foodborne Pathogens ◽  
Clinical Results ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Oral Bacteria ◽  
Resistant Bacteria ◽  
Wide Range

Pomegranates have been known for hundreds of years for their multiple health benefits, including antimicrobial activity. The recent surge in multidrug-resistant bacteria and the possibility of widespread global virus pandemics necessitate the need for additional preventative and therapeutic options to conventional drugs. Research indicates that pomegranates and their extracts may serve as natural alternatives due to their potency against a wide range of bacterial and viral pathogens. Nearly every part of the pomegranate plant has been tested for antimicrobial activities, including the fruit juice, peel, arils, flowers, and bark. Many studies have utilized pomegranate peel with success. There are various phytochemical compounds in pomegranate that have demonstrated antimicrobial activity, but most of the studies have found that ellagic acid and larger hydrolyzable tannins, such as punicalagin, have the highest activities. In some cases the combination of the pomegranate constituents offers the most benefit. The positive clinical results on pomegranate and suppression of oral bacteria are intriguing and worthy of further study. Much of the evidence for pomegranates’ antibacterial and antiviral activities against foodborne pathogens and other infectious disease organisms comes fromin vitrocell-based assays, necessitating further confirmation ofin vivoefficacy through human clinical trials.

scholarly journals Detection and Quantification of the Red Tide Dinoflagellate Karenia brevis by Real-Time Nucleic Acid Sequence-Based Amplification

2004 ◽  
Vol 70 (8) ◽  
pp. 4727-4732 ◽  
Author(s):  
Erica T. Casper ◽  
John H. Paul ◽  
Matthew C. Smith ◽  
Michael Gray
Keyword(s):  
Nucleic Acid ◽  
Real Time ◽  
Wildlife Conservation ◽  
Red Tide ◽  
Diagnostic Testing ◽  
Karenia Brevis ◽  
Nucleic Acid Sequence ◽  
Cell Counts ◽  
Wide Range

ABSTRACT Nucleic acid sequence-based amplification (NASBA) is an isothermal method of RNA amplification that has been previously used in clinical diagnostic testing. A real-time NASBA assay has been developed for the detection of rbcL mRNA from the red tide dinoflagellate Karenia brevis. This assay is sensitive to one K. brevis cell and 1.0 fg of in vitro transcript, with occasional detection of lower concentrations of transcript. The assay did not detect rbcL mRNA from a wide range of nontarget organisms and environmental clones, while 10 strains (all tested) of K. brevis were detected. By the use of standard curves based on time to positivity, concentrations of K. brevis in environmental samples were predicted by NASBA and classified into different levels of blooms per the Florida Fish and Wildlife Conservation Commission (FWC) system. NASBA classification matched FWC classification (based on cell counts) 72% of the time. Those samples that did not match were off by only one class. NASBA is sensitive, rapid, and effective and may be used as an additional or alternative method to detect and quantify K. brevis in the marine environment.

scholarly journals An Integrated HOCl-Producing E-Scaffold Is Active Against Monomicrobial and Polymicrobial Biofilms

2021 ◽  
Author(s):  
Laure Flurin ◽  
Yash S. Raval ◽  
Abdelrhman Mohamed ◽  
Kerryl E. Greenwood-Quaintance ◽  
Edison J. Cano ◽  
...  
Keyword(s):  
Low Dose ◽  
Hypochlorous Acid ◽  
Viable Cell ◽  
Chloride Ions ◽  
Resistant Bacteria ◽  
Wound Infections ◽  
Microbial Biofilms ◽  
Cell Counts ◽  
Acquired Antibiotic Resistance

Oxidizing agents like hypochlorous acid (HOCl) have antimicrobial activity. We developed an integrated electrochemical scaffold or ‘e-scaffold’ that delivers a continuous low dose of HOCl aimed at targeting microbial biofilms without exceeding concentrations toxic to humans, as a prototype of a device being developed to treat wound infections in humans. In this work, we tested the device against 33 isolates of bacteria (including isolates with acquired antibiotic resistance) grown as in vitro biofilms, alongside 12 combinations of dual-species in vitro biofilms. Biofilms were grown on the bottoms of 12-well plates for 24 hours. An integrated e-scaffold was placed atop each biofilm and polarized at 1.5V for 1, 2 or 4 hours. HOCl was produced electrochemically by oxidizing chloride ions (Cl-) in solution to chlorine (Cl2); dissolved Cl2 spontaneously dissociates in water to produce HOCl. The cumulative concentration of HOCl produced at the working electrode in each well was estimated to be 7.89, 13.46, and 29.50 mM after 1, 2 and 4 hours of polarization, respectively. Four hours of polarization caused an average reduction of 6.13 log10 CFU/cm2 (±1.99 log10 CFU/cm2) of viable cell counts of mono-species biofilms and 5.53 log10 CFU/cm2 (±2.31 log10 CFU/cm2) for the 12 dual-species biofilms studied. The described integrated e-scaffold reduces viable bacterial cell counts in biofilms formed by an array of antibiotic-susceptible and -resistant bacteria alone and in combination.

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