Extremophiles from unique ecosystems of Kazakhstan as potential producers of novel antimicrobial and anticancer agents

  • Azizan, Azliyati (PI)
  • Trenozhnikova, Lyudmila (CoI)
  • Berezin, Vladimir (CoI)
  • Beutler, John (CoI)
  • Zhulamanova, Ainur (Other participant)
  • Koshenov, Zhanat, (Other participant)
  • Iskhakova, Dinara (Student)
  • Alibekova, Meruyert (Student)

Project: Research project

Call title (Call ID)

ORAU grant

Project Description

Project overview and summary.
This project is a continuation of active collaboration with Scientists at the Institute of Microbiology and Virology (IMV) in Almaty Kazakhstan that has been ongoing for over ten years. In 2006, the PI was one of the collaborators on a grant funded for 3 years by the ISTC (International Science and Technology Center, on a project with the IMV entitled “The surveillance of new antibiotics from Kazakhstan soils actinomycetes, active against methicillin-resistant Staphylococci with multiple drug-resistances”. This project which was a collaboration with Dr. Trenozhnikova Lyudmila at the IMV, was successfully completed and described in two publications in 2012 and 2013. This continued project funded by NU focuses on the characterization of novel antibiotics isolated from Actinomycetes obtained from extreme environments of Kazakhstan that are active against drug-resistant hospital-associated pathogens as described in the proposal.
Overview of the overall proposed Project: three Specific Aims
Having characterized the producer organisms and extracts with known antagonistic activities against gram positive and gram negative pathogens, and with the antibiotic extracts produced and in storage, we are in a good position to expand on this study. We propose in this project application, three Specific Aims (SA’s). The first two SA’s (SA#1 and SA#2) are designed to further characterize the extracts; this is a series of effort to move forward the identification of active components within the extracts. For the third SA (SA#3), we propose to return to the field to further isolate and identify other extremophile strains that produce potent and novel antimicrobial or anticancer agents, using our established methods of sampling and culturing. These producer strains will be characterized further as in SA2#1 and #2, to identify antimicrobial or anticancer compounds that are novel, which could then be further developed for therapeutic applications and commercialization.

Key findings

2) Fresh antibiotic extracts from extremophilic actinomycetes were prepared in collaboration with the Institute of Microbiology and Virology (IMV) in Almaty. Their activities were tested on conditionally pathogenic bacteria, as well as hospital strains of multi-drug resistant pathogens, provided by the Republican Diagnostic Center (RDC) in Astana. High-Performance Liquid Chromatography (HPLC) was selected as a suitable chemical analysis to identify the active component of the extracts. Results of the HPLC analysis showed differential peaks on the extracts grown in different conditions, which suggest that according to the composition of the growth media, actinomycetes are able to produce different compounds that can inhibit the growth of other bacteria. These peaks also corresponded to the results of activity tests that were performed on conditionally pathogenic Staphylococcus aureus and Escherichia coli. These findings are included in the manuscript “Effect of different growth conditions on antimicrobial activity of extremophilic actinomycetes”, which will be completed and sent for publication by March 2018.
We plan to continue preparing extracts from extremophilic actinomycetes here at Nazarbayev University (NU), and perform all the related tests in the NUSOM laboratory. The extracts that have already shown antagonistic effect against pathogens and had differential peaks on HPLC will be prepared again to prepare more of the extracts for future testings and chemical analysis. Those extract will be fractionated using Bioassay-guided fractionation and each fraction will be tested for the inhibitory activity. This way it will be possible to separate the active component and identify it, using other chemical methods, such as mass spectrometry and NMR.
There is an increasing rate of deaths due to antimicrobial resistant (AMR) pathogens. This is the justification for our project which focuses on discovering novel antibiotic that would be effective against drug resistant hospital pathogens, which is the aim of our project. There has not been a research conducted on screening extremophilic actinomycetes under different growth conditions, since it can affect production of different, uncharacterized antibiotics. Students from different schools (SST) and departments within NUSOM have been involved in this project during summer internships, and as a part of the master’s thesis project. They have performed extraction, inhibitory activity tests, including disc diffusion assay and wells assay, and chemical tests, in collaboration with IMV and the RDC.
StatusActive
Effective start/end date10/1/1612/31/19

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Kazakhstan
Anti-Infective Agents
Antineoplastic Agents
Ecosystem
Drug Resistance
Pharmaceutical Preparations
Community Hospital
Drug Industry
Cross Infection
Penicillins
Disease Outbreaks
Anti-Bacterial Agents
Morbidity
Delivery of Health Care
Mutation
Mortality
Research
Population
Genes
Extremophiles