scholarly journals The therapeutic potential of bacteriocins as protein antibiotics

2017 ◽  
Vol 1 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Hannah M. Behrens ◽  
Anne Six ◽  
Daniel Walker ◽  
Colin Kleanthous
Keyword(s):  
Bacterial Infections ◽  
Therapeutic Potential ◽  
Ecological Niches ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Novel Treatments ◽  
Study Results ◽  
Protein Toxins

The growing incidence of antibiotic-resistant Gram-negative bacterial infections poses a serious threat to public health. Molecules that have yet to be exploited as antibiotics are potent protein toxins called bacteriocins that are produced by Gram-negative bacteria during competition for ecological niches. This review discusses the state of the art regarding the use for therapeutic purposes of two types of Gram-negative bacteriocins: colicin-like bacteriocins (CLBs) and tailocins. In addition to in vitro data, the potency of eight identified CLBs or tailocins has been demonstrated in diverse animal models of infection with no adverse effects for the host. Although the characteristics of bacteriocins will need further study, results obtained thus far regarding their in vivo potency, immunogenicity and low levels of resistance are encouraging. This leads the way for the development of novel treatments using bacteriocins as protein antibiotics.

scholarly journals TSPphg Lysin from the Extremophilic Thermus Bacteriophage TSP4 as a Potential Antimicrobial Agent against Both Gram-Negative and Gram-Positive Pathogenic Bacteria

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 192 ◽  
Author(s):  
Feng Wang ◽  
Xinyu Ji ◽  
Qiupeng Li ◽  
Guanling Zhang ◽  
Jiani Peng ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Infection Model ◽  
Bacterial Cells ◽  
Skin Damage ◽  
Gram Positive ◽  
Antibiotic Resistant ◽  
Gram Negative

New strategies against antibiotic-resistant bacterial pathogens are urgently needed but are not within reach. Here, we present in vitro and in vivo antimicrobial activity of TSPphg, a novel phage lysin identified from extremophilic Thermus phage TSP4 by sequencing its whole genome. By breaking down the bacterial cells, TSPphg is able to cause bacteria destruction and has shown bactericidal activity against both Gram-negative and Gram-positive pathogenic bacteria, especially antibiotic-resistant strains of Klebsiella pneumoniae, in which the complete elimination and highest reduction in bacterial counts by greater than 6 logs were observed upon 50 μg/mL TSPphg treatment at 37 °C for 1 h. A murine skin infection model further confirmed the in vivo efficacy of TSPphg in removing a highly dangerous and multidrug-resistant Staphylococcus aureus from skin damage and in accelerating wound closure. Together, our findings may offer a therapeutic alternative to help fight bacterial infections in the current age of mounting antibiotic resistance, and to shed light on bacteriophage-based strategies to develop novel anti-infectives.

Exploring the therapeutic potential of atorvastatin against Gram-positive and Gram-negative bacteria: In-silico, In-vitro and In- vivo evidence

2019 ◽  
Vol 19 ◽  
Author(s):  
Kamal Sethi ◽  
Arti Singh ◽  
Anoop Kumar
Keyword(s):  
Mtt Assay ◽  
In Silico ◽  
Bacterial Infections ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Bacterial Strains ◽  
Study Results ◽  
Reference Ligand

The incidences of opportunistic bacterial infections have increased from the past two decades or threaten to increase in the near future. Inspite of the availability of various classes of antibiotics, bacterial infections are not handled properly.Thus, in the present study, we have repurposed atorvastatin against various types of bacterial strains by using in-silico, in-vitro, and in-vivo studies. Further, preliminary safety study was conducted using MTT assay. In-silico study results have revealed that atorvastatin hasgood interaction with various targets of bacterial cell as that of reference ligand. However, under in-vitro conditions, we have foundthat atorvastatin was effective at higher concentration(>128 μg/ml) against various bacterial strains. Thus, further, atorvastatin was tested in combination with standard antibiotics and has shown synergistic effect. The MTT assay results have revealed non-cytotoxic activity of atorvastatin. In conclusion, atorvastatin in combination with standard drugs could be developed as an antibacterial agent.

scholarly journals ZN148 Is a Modular Synthetic Metallo-β-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens In Vivo

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Ørjan Samuelsen ◽  
Ove Alexander Høgmoen Åstrand ◽  
Christopher Fröhlich ◽  
Adam Heikal ◽  
Susann Skagseth ◽  
...  
Keyword(s):  
Active Site ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Functional Space ◽  
Bactericidal Effect ◽  
Gram Negative ◽  
Content Type

ABSTRACT Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical Enterobacterales strains (n = 234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM, and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ∼30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modeling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor that is capable of operating in a functional space not presently filled by any clinically approved compound.

scholarly journals Hitchhiking with Nature: Snake Venom Peptides to Fight Cancer and Superbugs

Toxins ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 255 ◽  
Author(s):  
Clara Pérez-Peinado ◽  
Sira Defaus ◽  
David Andreu
Keyword(s):  
Therapeutic Potential ◽  
State Of The Art ◽  
Resistant Bacteria ◽  
Snake Venoms ◽  
Antibiotic Resistant ◽  
Anticancer Peptides ◽  
Therapeutic Development ◽  
Drug Leads

For decades, natural products in general and snake venoms (SV) in particular have been a rich source of bioactive compounds for drug discovery, and they remain a promising substrate for therapeutic development. Currently, a handful of SV-based drugs for diagnosis and treatment of various cardiovascular disorders and blood abnormalities are on the market. Likewise, far more SV compounds and their mimetics are under investigation today for diverse therapeutic applications, including antibiotic-resistant bacteria and cancer. In this review, we analyze the state of the art regarding SV-derived compounds with therapeutic potential, focusing on the development of antimicrobial and anticancer drugs. Specifically, information about SV peptides experimentally validated or predicted to act as antimicrobial and anticancer peptides (AMPs and ACPs, respectively) has been collected and analyzed. Their principal activities both in vitro and in vivo, structures, mechanisms of action, and attempts at sequence optimization are discussed in order to highlight their potential as drug leads.

scholarly journals Blue laser light inhibits biofilm formation in vitro and in vivo by inducing oxidative stress

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Katia Rupel ◽  
Luisa Zupin ◽  
Giulia Ottaviani ◽  
Iris Bertani ◽  
Valentina Martinelli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Biofilm Formation ◽  
Mammalian Cells ◽  
Bacterial Infections ◽  
Laser Light ◽  
Therapeutic Potential ◽  
Blue Laser ◽  
Data Set

Abstract Resolution of bacterial infections is often hampered by both resistance to conventional antibiotic therapy and hiding of bacterial cells inside biofilms, warranting the development of innovative therapeutic strategies. Here, we report the efficacy of blue laser light in eradicating Pseudomonas aeruginosa cells, grown in planktonic state, agar plates and mature biofilms, both in vitro and in vivo, with minimal toxicity to mammalian cells and tissues. Results obtained using knock-out mutants point to oxidative stress as a relevant mechanism by which blue laser light exerts its anti-microbial effect. Finally, the therapeutic potential is confirmed in a mouse model of skin wound infection. Collectively, these data set blue laser phototherapy as an innovative approach to inhibit bacterial growth and biofilm formation, and thus as a realistic treatment option for superinfected wounds.

scholarly journals Phage Therapy as a Focused Management Strategy in Aquaculture

2021 ◽  
Vol 22 (19) ◽  
pp. 10436
Author(s):  
José Ramos-Vivas ◽  
Joshua Superio ◽  
Jorge Galindo-Villegas ◽  
Félix Acosta
Keyword(s):  
Bacterial Infections ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Control Strategies ◽  
Bacterial Species ◽  
Lytic Enzymes ◽  
Wide Range ◽  
Cultured Fish

Therapeutic bacteriophages, commonly called as phages, are a promising potential alternative to antibiotics in the management of bacterial infections of a wide range of organisms including cultured fish. Their natural immunogenicity often induces the modulation of a variated collection of immune responses within several types of immunocytes while promoting specific mechanisms of bacterial clearance. However, to achieve standardized treatments at the practical level and avoid possible side effects in cultivated fish, several improvements in the understanding of their biology and the associated genomes are required. Interestingly, a particular feature with therapeutic potential among all phages is the production of lytic enzymes. The use of such enzymes against human and livestock pathogens has already provided in vitro and in vivo promissory results. So far, the best-understood phages utilized to fight against either Gram-negative or Gram-positive bacterial species in fish culture are mainly restricted to the Myoviridae and Podoviridae, and the Siphoviridae, respectively. However, the current functional use of phages against bacterial pathogens of cultured fish is still in its infancy. Based on the available data, in this review, we summarize the current knowledge about phage, identify gaps, and provide insights into the possible bacterial control strategies they might represent for managing aquaculture-related bacterial diseases.

scholarly journals In vitro and in vivo antibacterial efficacies of CFC-222, a new fluoroquinolone.

1997 ◽  
Vol 41 (10) ◽  
pp. 2209-2213 ◽  
Author(s):  
J H Kim ◽  
J A Kang ◽  
Y G Kim ◽  
J W Kim ◽  
J H Lee ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Protective Efficacy ◽  
Horse Serum ◽  
The Other ◽  
Infection Model ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli

CFC-222 is a novel fluoroquinolone containing a C-7 bicyclic amine moiety with potent antibacterial activities against gram-positive, gram-negative, and anaerobic organisms. We compared the in vitro and in vivo activities of CFC-222 with those of ciprofloxacin, ofloxacin, and lomefloxacin. CFC-222 was more active than the other fluoroquinolones tested against gram-positive bacteria. CFC-222 was particularly active against Streptococcus pneumoniae (MIC at which 90% of isolates are inhibited [MIC90], 0.2 microg/ml), Staphylococcus aureus (MIC90, 0.2 microg/ml for ciprofloxacin-susceptible strains), and Enterococcus faecalis (MIC90, 0.39 microg/ml). Against Escherichia coli and other members of the family Enterobacteriaceae, CFC-222 was slightly less active than ciprofloxacin (MIC90s for E. coli, 0.1 and 0.025 microg/ml, respectively). The in vitro activity of CFC-222 was not influenced by inoculum size, medium composition, or the presence of horse serum. However, its activity was decreased significantly by a change in the pH of the medium from 7.0 to 6.0, as was the case for the other quinolones tested. The in vivo protective efficacy of CFC-222 by oral administration was greater than those of the other quinolones tested in a mouse model of intraperitoneally inoculated systemic infection caused by S. aureus. CFC-222 exhibited efficacy comparable to that of ciprofloxacin in the same model of infection caused by gram-negative organisms, such as E. coli and Klebsiella pneumoniae. In this infection model, CFC-222 was slightly less active than ciprofloxacin against Pseudomonas aeruginosa. These results suggest that CFC-222 may be a promising therapeutic agent in various bacterial infections.

scholarly journals In Vitro and In Vivo Antibacterial Activities of Heteroaryl Isothiazolones against Resistant Gram-Positive Pathogens

2007 ◽  
Vol 51 (4) ◽  
pp. 1259-1267 ◽  
Author(s):  
Michael J. Pucci ◽  
Jijun Cheng ◽  
Steven D. Podos ◽  
Christy L. Thoma ◽  
Jane A. Thanassi ◽  
...  
Keyword(s):  
Legionella Pneumophila ◽  
Standard Dose ◽  
Antibacterial Activities ◽  
Gram Positive ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACT The activities of several tricyclic heteroaryl isothiazolones (HITZs) against an assortment of gram-positive and gram-negative clinical isolates were assessed. These compounds target bacterial DNA replication and were found to possess broad-spectrum activities especially against gram-positive strains, including antibiotic-resistant staphylococci and streptococci. These included methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-nonsusceptible staphylococci, and quinolone-resistant strains. The HITZs were more active than the comparator antimicrobials in most cases. For gram-negative bacteria, the tested compounds were less active against members of the family Enterobacteriaceae but showed exceptional potencies against Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. Good activity against several anaerobes, as well as Legionella pneumophila and Mycoplasma pneumoniae, was also observed. Excellent bactericidal activity against staphylococci was observed in time-kill assays, with an approximately 3-log drop in the numbers of CFU/ml occurring after 4 h of exposure to compound. Postantibiotic effects (PAEs) of 2.0 and 1.7 h for methicillin-susceptible S. aureus and MRSA strains, respectively, were observed, and these were similar to those seen with moxifloxacin at 10× MIC. In vivo efficacy was demonstrated in murine infections by using sepsis and thigh infection models. The 50% protective doses were ≤1 mg/kg of body weight against S. aureus in the sepsis model, while decreases in the numbers of CFU per thigh equal to or greater than those detected in animals treated with a standard dose of vancomycin were seen in the animals with thigh infections. Pharmacokinetic analyses of treated mice indicated exposures similar to those to ciprofloxacin at equivalent dose levels. These promising initial data suggest further study on the use of the HITZs as antibacterial agents.

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 Integrated endotoxin-adsorption and antibacterial properties of platelet-membrane-coated copper silicate hollow microspheres for wound healing

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zaihui Peng ◽  
Xiaochun Zhang ◽  
Long Yuan ◽  
Ting Li ◽  
Yajie Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Bacterial Infections ◽  
Antibacterial Properties ◽  
Platelet Membrane ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
The Impact ◽  
Copper Silicate

AbstractSerious infection caused by drug-resistant gram-negative bacteria and their secreted toxins (e.g., lipopolysaccharide) is a serious threat to human health. Thus, treatment strategies that efficiently kill bacteria and reducing the impact of their toxins simultaneously are urgently required. Herein, a novel antibacterial platform composed of a mesoporous copper silicate microsphere (CSO) core and a platelet membrane (PM) shell was prepared (CSO@PM). CSO@PM specifically targets bacteria owing to formyl peptide receptors on the PM and, combined with photothermal therapy (PTT), exhibits highly effective bacter icidal activity. Importantly, CSO@PM can adsorb lipopolysaccharide secreted by gram-negative bacteria, resulting in inflammation reduction. Thus, CSO@PM stimulates re-epithelialization and granulation-tissue formation, promoting wound healing. Moreover, this antibacterial platform exhibits no obvious toxicity at all the test concentrations in vitro and in vivo. Thus, CSO@PM exhibits a robust antibacterial effect and a strong toxin-adsorption capacity, facilitating the clinical treatment of many bacterial infections and the development of next-generation antibacterial nanoagents. Graphical Abstract

Sign in / Sign up

Export Citation Format

Share Document