scholarly journals Evaluation of the Efficacy of a Bacteriophage in the Treatment of Pneumonia Induced by Multidrug ResistanceKlebsiella pneumoniaein Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Fang Cao ◽  
Xitao Wang ◽  
Linhui Wang ◽  
Zhen Li ◽  
Jian Che ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Burst Size ◽  
Multidrug Resistant ◽  
Lung Lesion ◽  
Lytic Bacteriophage ◽  
Short Latent Period ◽  
Dose Dependent ◽  
Antibiotic Control

Multidrug-resistantKlebsiella pneumoniae(MRKP) has steadily grown beyond antibiotic control. However, a bacteriophage is considered to be a potential antibiotic alternative for treating bacterial infections. In this study, a lytic bacteriophage, phage 1513, was isolated using a clinical MRKP isolate KP 1513 as the host and was characterized. It produced a clear plaque with a halo and was classified as Siphoviridae. It had a short latent period of 30 min, a burst size of 264 and could inhibit KP 1513 growthin vitrowith a dose-dependent pattern. Intranasal administration of a single dose of 2 × 109 PFU/mouse 2 h after KP 1513 inoculation was able to protect mice against lethal pneumonia. In a sublethal pneumonia model, phage-treated mice exhibited a lower level ofK. pneumoniaeburden in the lungs as compared to the untreated control. These mice lost less body weight and exhibited lower levels of inflammatory cytokines in their lungs. Lung lesion conditions were obviously improved by phage therapy. Therefore, phage 1513 has a great effectin vitroandin vivo, which has potential to be used as an alternative to an antibiotic treatment of pneumonia that is caused by the multidrug-resistantK. pneumoniae.

scholarly journals Clavanin A Improves Outcome of Complications from Different Bacterial Infections

2014 ◽  
Vol 59 (3) ◽  
pp. 1620-1626 ◽  
Author(s):  
Osmar N. Silva ◽  
Isabel C. M. Fensterseifer ◽  
Elaine A. Rodrigues ◽  
Hortência H. S. Holanda ◽  
Natasha R. F. Novaes ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Toxicity Tests ◽  
Cytotoxic Activities ◽  
Content Type ◽  
Wound Model ◽  
Acute Toxicity Tests

ABSTRACTThe rapid increase in the incidence of multidrug-resistant infections today has led to enormous interest in antimicrobial peptides (AMPs) as suitable compounds for developing unusual antibiotics. In this study, clavanin A, an antimicrobial peptide previously isolated from the marine tunicateStyela clava, was selected as a purposeful molecule that could be used in controlling infection and further synthesized. Clavanin A wasin vitroevaluated againstStaphylococcus aureusandEscherichia colias well as toward L929 mouse fibroblasts and skin primary cells (SPCs). Moreover, this peptide was challenged here in anin vivowound and sepsis model, and the immune response was also analyzed. Despite displaying clearin vitroantimicrobial activity toward Gram-positive and -negative bacteria, clavanin A showed no cytotoxic activities against mammalian cells, and in acute toxicity tests, no adverse reaction was observed at any of the concentrations. Moreover, clavanin A significantly reduced theS. aureusCFU in an experimental wound model. This peptide also reduced the mortality of mice infected withE. coliandS. aureusby 80% compared with that of control animals (treated with phosphate-buffered saline [PBS]): these data suggest that clavanin A prevents the start of sepsis and thereby reduces mortality. These data suggest that clavanin A is an AMP that could improve the development of novel peptide-based strategies for the treatment of wound and sepsis infections.

scholarly journals Isolation and characterization of a lytic bacteriophage against Pseudomonas aeruginosa

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sonika Sharma ◽  
Sibnarayan Datta ◽  
Soumya Chatterjee ◽  
Moumita Dutta ◽  
Jhuma Samanta ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Burst Size ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Potential Candidate ◽  
Lytic Bacteriophage ◽  
Isolation And Characterization ◽  
Phage Proteins

AbstractIn recent years, the use of bacteriophages (or 'phages') against multidrug-resistant (MDR) bacteria including Pseudomonas aeruginosa has drawn considerable attention, globally. In this work, we report the isolation and detailed characterization of a highly lytic Pseudomonasphage DRL-P1 isolated from wastewater. Under TEM, DRL-P1 appeared as a member of the phage family Myoviridae. DRL-P1 featured rapid adsorption (~ 5 min), short-latency (~ 30 min), and large burst size (~ 100 PFU per infected cell). DRL-P1 can withstand a wide temperature range (4 °C to 40 °C) and pH (5.0 to 10.0) conditions. The 66,243 bp DRL-P1 genome (MN564818) encodes at least 93 ORFs, of which 36 were functionally annotated based on homology with similar phage proteins available in the databases. Comparative analyses of related genomes suggest an independent evolutionary history and discrete taxonomic position of DRL-P1 within genus Pbunavirus. No toxin or antibiotic resistance genes was identified. DRL-P1 is tolerant to lyophilization and encapsulation techniques and retained lytic activity even after 18 months of storage. We also demonstrated decontaminating potentials of DRL-P1 in vitro, on an artificially contaminated cover-slip model. To the best of our knowledge, this is the first Pbunavirus to be reported from India. Our study suggests DRL-P1 as a potential candidate for various applications.

scholarly journals Deimmunized Lysostaphin Synergizes with Small-molecule Chemotherapies and Re-sensitizes MRSA to β-Lactam Antibiotics

2020 ◽  
pp. AAC.01707-20
Author(s):  
Yongliang Fang ◽  
Jack R. Kirsch ◽  
Liang Li ◽  
Seth A. Brooks ◽  
Spencer Heim ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Standard Of Care ◽  
Rapid Onset ◽  
Multidrug Resistant ◽  
Genetically Engineered ◽  
High Potency ◽  
Onset Of Action ◽  
New Antibiotics

There is an urgent need for novel agents to treat drug-resistant bacterial infections, such as multidrug-resistant Staphylococcus aureus (MRSA). Desirable properties for new antibiotics include high potency, narrow species selectivity, low propensity to elicit new resistance phenotypes, and synergy with standard of care (SOC) chemotherapies. Here, we describe analysis of the anti-MRSA potential exhibited by F12, an innovative anti-MRSA lysin that has been genetically engineered to evade detrimental antidrug immune responses in human patients. F12 possesses high potency and rapid onset of action, it has narrow selectivity against pathogenic Staphylococci, and it manifests synergy with numerous SOC antibiotics. Additionally, resistance to F12 and β-lactam antibiotics appears mutually exclusive, and importantly we provide evidence that F12 re-sensitizes normally resistant MRSA strains to β-lactams both in vitro and in vivo. These results suggest that combinations of F12 and SOC antibiotics could be a promising new approach to treating refractory S. aureus infections.

An effective zinc phthalocyanine derivative against multidrug-resistant bacterial infection

2017 ◽  
Vol 21 (03) ◽  
pp. 205-210 ◽  
Author(s):  
Dong Wang ◽  
Yuxiang Zhang ◽  
Shufeng Yan ◽  
Zihan Chen ◽  
Yicai Deng ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Red Light ◽  
Multidrug Resistant ◽  
Zinc Phthalocyanine ◽  
In Vivo Studies ◽  
Infection Model ◽  
Clinical Test ◽  
Phthalocyanine Derivative

Bacterial skin and soft tissue infections are abundant worldwide. The rise in the incidence of multidrug-resistant (MDR) bacterial infections has made the need for alternative means of treatment more pressing. We herein report a zinc phthalocyanine derivative, pentalysine [Formula: see text]-carbonylphthalocyanine zinc (ZnPc-(Lys)[Formula: see text] and its strong capability of killing nosocomial MDR bacteria, including MDR-Escherichia coli and MDR-Acinetobacter baumannii. In vitro studies, we observed that ZnPc-(Lys)5 in micromolar concentrations killed above MDR bacteria in 6~6.5 log10 orders with only 5-min illumination of red light at a dosage of 12.75 J/cm[Formula: see text]. Further in vivo studies on a mouse infection model demonstrated that ZnPc-(Lys)5 efficiently inhibited the MDR bacterial growth after one-time photodynamic antibacterial therapy and, interestingly, significantly accelerated the wound healing. Putting together, our findings establish ZnPc-(Lys)5 as a potent antimicrobial candidate for the clinical test on localized infection.

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.

scholarly journals Conjugative Delivery of CRISPR-Cas9 for the Selective Depletion of Antibiotic-Resistant Enterococci

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Marinelle Rodrigues ◽  
Sara W. McBride ◽  
Karthik Hullahalli ◽  
Kelli L. Palmer ◽  
Breck A. Duerkop
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Conjugative Plasmid ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Resistance Determinants

ABSTRACT The innovation of new therapies to combat multidrug-resistant (MDR) bacteria is being outpaced by the continued rise of MDR bacterial infections. Of particular concern are hospital-acquired infections (HAIs) that are recalcitrant to antibiotic therapies. The Gram-positive intestinal pathobiont Enterococcus faecalis is associated with HAIs, and some strains are MDR. Therefore, novel strategies to control E. faecalis populations are needed. We previously characterized an E. faecalis type II CRISPR-Cas system and demonstrated its utility in the sequence-specific removal of antibiotic resistance determinants. Here, we present work describing the adaption of this CRISPR-Cas system into a constitutively expressed module encoded on a pheromone-responsive conjugative plasmid that efficiently transfers to E. faecalis for the selective removal of antibiotic resistance genes. Using in vitro competition assays, we show that these CRISPR-Cas-encoding delivery plasmids, or CRISPR-Cas antimicrobials, can reduce the occurrence of antibiotic resistance in enterococcal populations in a sequence-specific manner. Furthermore, we demonstrate that deployment of CRISPR-Cas antimicrobials in the murine intestine reduces the occurrence of antibiotic-resistant E. faecalis by several orders of magnitude. Finally, we show that E. faecalis donor strains harboring CRISPR-Cas antimicrobials are immune to uptake of antibiotic resistance determinants in vivo. Our results demonstrate that conjugative delivery of CRISPR-Cas antimicrobials may be adaptable for future deployment from probiotic bacteria for exact targeting of defined MDR bacteria or for precision engineering of polymicrobial communities in the mammalian intestine.

scholarly journals Characterization of a Novel Bacteriophage swi2 Harboring Two Lysins Can Naturally Lyse Escherichia coli

2021 ◽  
Vol 12 ◽  
Author(s):  
Bingrui Sui ◽  
Xin Qi ◽  
Xiaoxue Wang ◽  
Huiying Ren ◽  
Wenhua Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
High Titer ◽  
Burst Size ◽  
Multidrug Resistant ◽  
Biological Characteristics ◽  
Query Coverage ◽  
Pig Farm ◽  
Ph Range

The novel virulent Siphoviridae bacteriophage swi2 was isolated from a pig farm, and its biological characteristics, genome architecture, and infection-related properties were characterized. Phage swi2 has a high titer of 1.01 × 1012 PFU/mL with good tolerance to UV rays and remains stable in the pH range of 6–10 and at temperatures less than 50°C. One-step growth analysis revealed that phage swi2 had a 25 min latent period with a large burst size (1,000 PFU/cell). The biological characteristics indicated that swi2 had good host infectivity and effective lytic activities. The genome of phage swi2 is composed of 47,611 bp with a G + C content of 46.50%. Eighty-nine orfs were predicted, and only 18 of them have known functions. No virulence genes or drug resistance genes were found in the genome. Genome sequence comparison of phage swi2 showed that there were a total of 10 homologous phages in the database with low similarity (less than 92.51% nucleotide identity and 66% query coverage). The predicted host lysis-related genes of phage swi2 consist of one holin, two endolysins, and Rz/Rz1 equivalents. Antibacterial activity assays showed that both endolysins could naturally reduce the host Escherichia coli 51 titers by -1 log unit both in vitro and in vivo, EDTA showed no obvious synergistic action, and holin had no lytic effects on the host cell. These results provide necessary information for the development of antibiotic alternatives for the treatment of multidrug-resistant Escherichia coli infection.

scholarly journals Erianin against Staphylococcus aureus Infection via Inhibiting Sortase A

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 385 ◽  
Author(s):  
Ping Ouyang ◽  
Xuewen He ◽  
Zhong-Wei Yuan ◽  
Zhong-Qiong Yin ◽  
Hualin Fu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Hydrophobic Interactions ◽  
Multidrug Resistant ◽  
Vital Role ◽  
Surface Proteins ◽  
Dynamics Simulation ◽  
Sortase A

With continuous emergence and widespread of multidrug-resistant Staphylococcus aureus infections, common antibiotics have become ineffective in treating these infections in the clinical setting. Anti-virulence strategies could be novel, effective therapeutic strategies against drug-resistant bacterial infections. Sortase A (srtA), a transpeptidase in gram-positive bacteria, can anchor surface proteins that play a vital role in pathogenesis of these bacteria. SrtA is known as a potential antivirulent drug target to treat bacterial infections. In this study, we found that erianin, a natural bibenzyl compound, could inhibit the activity of srtA in vitro (half maximal inhibitory concentration—IC50 = 20.91 ± 2.31 μg/mL, 65.7 ± 7.2 μM) at subminimum inhibitory concentrations (minimum inhibitory concentrations—MIC = 512 μg/mL against S. aureus). The molecular mechanism underlying the inhibition of srtA by erianin was identified using molecular dynamics simulation: erianin binds to srtA residues Ile182, Val193, Trp194, Arg197, and Ile199, forming a stable bond via hydrophobic interactions. In addition, the activities of S. aureus binding to fibronectin and biofilm formation were inhibited by erianin, when co-culture with S. aureus. In vivo, erianin could improve the survival in mice that infected with S. aureus by tail vein injection. Experimental results showed that erianin is a potential novel therapeutic compound against S. aureus infections via affecting srtA.

scholarly journals Antimicrobial Activity Study of Chinese Medicine Madeng’ai

2021 ◽  
Author(s):  
Zhenrong Tang ◽  
Yannan Zhao ◽  
Zaiqi Zhang ◽  
Huan Yue ◽  
Dan Wang ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Chinese Medicine ◽  
Bacterial Infections ◽  
Multidrug Resistant ◽  
Control Treatment ◽  
Resistant Bacteria ◽  
Mice Model ◽  
Bacteria Growth

Abstract Background Due to the overuse of antibiotics, many multidrug-resistant bacteria have emerged, which brings huge challenges to the clinical treatment of bacterial infections. New products for anti-infection are necessary. Methods Madeng’ai powder was added with Milli-Q water or LB culture and autoclaved to prepare medicine suspension at different concentration. Bacteria were cultured in LB with different concentration of Madeng’ai. and swab on LB agar plates to get minimal inhibitory concentration (MIC) of Madeng’ai. Mice back was cut to make wound and MRSA/PAE suspension was injected in the wound area. Then swab with Madeng’ai extracts. Bacteria growth of infected secretions was checked on LB agar, and Hematoxylin and eosin (H&E) staining was performed for Histological analysis of skin tissues infected with bacteria after Madeng’ai and PBS (control) treatment. Results Madeng’ai could widely inhibit E.faecalis, Pseudomonas aeruginosa (PAE), Klebsiella pneumoniae (K.pneumoniae) and Acinetobacter baumannii (A.baumannii) at concentration of 4.0 mg/ml. The mice model also showed that Madeng’ai had imposed restrictions on MRSA and PAE growth in vivo. Conclusion Here, we report that a new Chinese medicine Madeng’ai has antimicrobial activity functions in vitro and in vivo. These data briefly showed that Madeng’ai functioned on antimicrobial and provided a new consideration for an antibiosis product.

scholarly journals Antibacterial Effect of Silver Nanoparticles Synthesized Using Murraya koenigii (L.) against Multidrug-Resistant Pathogens

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Faizan Abul Qais ◽  
Anam Shafiq ◽  
Haris M. Khan ◽  
Fohad M. Husain ◽  
Rais A. Khan ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Bacterial Infections ◽  
Enteric Bacteria ◽  
Multidrug Resistant ◽  
Murraya Koenigii ◽  
E Coli ◽  
Vis Spectroscopy ◽  
Zones Of Inhibition

Development of multidrug resistance among pathogens has become a global problem for chemotherapy of bacterial infections. Extended-spectrum β-lactamase- (ESβL-) producing enteric bacteria and methicillin-resistant Staphylococcus aureus (MRSA) are the two major groups of problematic MDR bacteria that have evolved rapidly in the recent past. In this study, the aqueous extract of Murraya koenigii leaves was used for synthesis of silver nanoparticles. The synthesized MK-AgNPs were characterized using UV-vis spectroscopy, FTIR, XRD, SEM, and TEM, and their antibacterial potential was evaluated on multiple ESβL-producing enteric bacteria and MRSA. The nanoparticles were predominantly found to be spheroidal with particle size distribution in the range of 5–20 nm. There was 60.86% silver content in MK-AgNPs. Evaluation of antibacterial activity by the disc-diffusion assay revealed that MK-AgNPs effectively inhibited the growth of test pathogens with varying sized zones of inhibition. The MICs of MK-AgNPs against both MRSA and methicillin-sensitive S. aureus (MSSA) strains were 32 μg/ml, while for ESβL-producing E. coli, it ranged from 32 to 64 μg/ml. The control strain of E. coli (ECS) was relatively more sensitive with an MIC of 16 μg/ml. The MBCs were in accordance with the respective MICs. Analysis of growth kinetics revealed that the growth of all tested S. aureus strains was inhibited (∼90%) in presence of 32 μg/ml of MK-AgNPs. The sensitive strain of E. coli (ECS) showed least resistance to MK-AgNPs with >81% inhibition at 16 μg/ml. The present investigation revealed an encouraging result on in vitro efficacy of green synthesized MK-AgNPs and needed further in vivo assessment for its therapeutic efficacy against MDR bacteria.

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