scholarly journals Unbiased Identification of Angiogenin as an Endogenous Antimicrobial Protein With Activity Against Virulent Mycobacterium tuberculosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Reiner Noschka ◽  
Fabian Gerbl ◽  
Florian Löffler ◽  
Jan Kubis ◽  
Armando A. Rodríguez ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Antibiotic Treatment ◽  
Computational Analysis ◽  
Antimicrobial Protein ◽  
Fast Growing ◽  
Single Compound ◽  
Resistant Strains ◽  
Drug Resistant Strains

Tuberculosis is a highly prevalent infectious disease with more than 1.5 million fatalities each year. Antibiotic treatment is available, but intolerable side effects and an increasing rate of drug-resistant strains of Mycobacterium tuberculosis (Mtb) may hamper successful outcomes. Antimicrobial peptides (AMPs) offer an alternative strategy for treatment of infectious diseases in which conventional antibiotic treatment fails. Human serum is a rich resource for endogenous AMPs. Therefore, we screened a library generated from hemofiltrate for activity against Mtb. Taking this unbiased approach, we identified Angiogenin as the single compound in an active fraction. The antimicrobial activity of endogenous Angiogenin against extracellular Mtb could be reproduced by synthetic Angiogenin. Using computational analysis, we identified the hypothetical active site and optimized the lytic activity by amino acid exchanges. The resulting peptide-Angie1-limited the growth of extra‐ and intracellular Mtb and the fast-growing pathogens Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Toward our long-term goal of evaluating Angie1 for therapeutic efficacy in vivo, we demonstrate that the peptide can be efficiently delivered into human macrophages via liposomes and is not toxic for zebrafish embryos. Taken together, we define Angiogenin as a novel endogenous AMP and derive the small, bioactive fragment Angie1, which is ready to be tested for therapeutic activity in animal models of tuberculosis and infections with fast-growing bacterial pathogens.

scholarly journals Multistage antiplasmodial activity of hydroxyethylamine compounds, in vitro and in vivo evaluations

RSC Advances ◽  
2020 ◽  
Vol 10 (58) ◽  
pp. 35516-35530
Author(s):  
Neha Sharma ◽  
Yash Gupta ◽  
Meenakshi Bansal ◽  
Snigdha Singh ◽  
Prateek Pathak ◽  
...  
Keyword(s):  
Human Population ◽  
Antiplasmodial Activity ◽  
Drug Resistant ◽  
Fast Growing ◽  
Resistant Strains ◽  
Global Threat ◽  
Drug Resistant Strains

Malaria, a global threat to the human population, remains a challenge partly due to the fast-growing drug-resistant strains of Plasmodium species.

scholarly journals In Vitro Efficacies, ADME, and Pharmacokinetic Properties of Phenoxazine Derivatives Active against Mycobacterium tuberculosis

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Lloyd Tanner ◽  
Joanna C. Evans ◽  
Ronnett Seldon ◽  
Audrey Jordaan ◽  
Digby F. Warner ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Infected Animal ◽  
Mechanisms Of Action ◽  
Drug Resistant ◽  
Content Type ◽  
Pharmacokinetic Properties ◽  
Resistant Strains ◽  
Drug Resistant Strains

ABSTRACT Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a leading infectious killer globally, demanding the urgent development of faster-acting drugs with novel mechanisms of action. Riminophenazines such as clofazimine are clinically efficacious against both drug-susceptible and drug-resistant strains of M. tuberculosis. We determined the in vitro anti-M. tuberculosis activities, absorption, distribution, metabolism, and excretion properties, and in vivo mouse pharmacokinetics of a series of structurally related phenoxazines. One of these, PhX1, displayed promising drug-like properties and potent in vitro efficacy, supporting its further investigation in an M. tuberculosis-infected animal model.

Evaluation of efflux pump gene expression among drug susceptible and drug resistant strains of Mycobacterium tuberculosis from Iran

2015 ◽  
Vol 36 ◽  
pp. 23-26 ◽  
Author(s):  
Jalil Kardan Yamchi ◽  
Mehri Haeili ◽  
Seifu Gizaw Feyisa ◽  
Hossein Kazemian ◽  
Abdolrazagh Hashemi Shahraki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mycobacterium Tuberculosis ◽  
Efflux Pump ◽  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals In Vitro and In Vivo Antimalarial Activities of a Carbohydrate Antibiotic, Prumycin, against Drug-resistant Strains of Plasmodia

2004 ◽  
Vol 57 (6) ◽  
pp. 400-402 ◽  
Author(s):  
KAZUHIKO OTOGURO ◽  
AKI ISHIYAMA ◽  
MIYUKI KOBAYASHI ◽  
HITOMI SEKIGUCHI ◽  
TAKASHI IZUHARA ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Resistant Strains ◽  
Drug Resistant Strains

scholarly journals What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of Streptococcus pneumoniae ?

2009 ◽  
Vol 7 (47) ◽  
pp. 905-919 ◽  
Author(s):  
Caroline Colijn ◽  
Ted Cohen ◽  
Christophe Fraser ◽  
William Hanage ◽  
Edward Goldstein ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Infectious Diseases ◽  
Multiple Infection ◽  
Drug Resistant ◽  
Host Interactions ◽  
Resistant Strains ◽  
Neutral Models ◽  
Drug Resistant Strains ◽  
And Control

The rise of antimicrobial resistance in many pathogens presents a major challenge to the treatment and control of infectious diseases. Furthermore, the observation that drug-resistant strains have risen to substantial prevalence but have not replaced drug-susceptible strains despite continuing (and even growing) selective pressure by antimicrobial use presents an important problem for those who study the dynamics of infectious diseases. While simple competition models predict the exclusion of one strain in favour of whichever is ‘fitter’, or has a higher reproduction number, we argue that in the case of Streptococcus pneumoniae there has been persistent coexistence of drug-sensitive and drug-resistant strains, with neither approaching 100 per cent prevalence. We have previously proposed that models seeking to understand the origins of coexistence should not incorporate implicit mechanisms that build in stable coexistence ‘for free’. Here, we construct a series of such ‘structurally neutral’ models that incorporate various features of bacterial spread and host heterogeneity that have been proposed as mechanisms that may promote coexistence. We ask to what extent coexistence is a typical outcome in each. We find that while coexistence is possible in each of the models we consider, it is relatively rare, with two exceptions: (i) allowing simultaneous dual transmission of sensitive and resistant strains lets coexistence become a typical outcome, as does (ii) modelling each strain as competing more strongly with itself than with the other strain, i.e. self-immunity greater than cross-immunity. We conclude that while treatment and contact heterogeneity can promote coexistence to some extent, the in-host interactions between strains, particularly the interplay between coinfection, multiple infection and immunity, play a crucial role in the long-term population dynamics of pathogens with drug resistance.

Mycobacterium tuberculosis topoisomerases and EthR as the targets for new anti-TB drugs development

2019 ◽  
Vol 11 (16) ◽  
pp. 2193-2203
Author(s):  
Rafal Sawicki ◽  
Grazyna Ginalska
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Short Review ◽  
Drug Resistant ◽  
Dna Topoisomerases ◽  
Antituberculosis Drugs ◽  
Drug Candidates ◽  
Computational Sciences ◽  
Resistant Strains ◽  
Drug Resistant Strains ◽  
New Strategies

The significant increase in the detection of drug-resistant strains of Mycobacterium tuberculosis caused an urgent need for the discovery new antituberculosis drugs. Development of bioinformatics and computational sciences enabled the progress of new strategies leading to design, discovery and identification of a series of interesting drug candidates. In this short review, we would like to present recently discovered compounds targeting important mycobacterial proteins: DNA topoisomerases and the transcriptional repressor of EthA monooxygenase – EthR.

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