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Adv Pharm Bull. 2017;7(2): 179-187.
doi: 10.15171/apb.2017.022
PMID: 28761819
PMCID: PMC5527231
Scopus ID: 85021392454
  Abstract View: 2070
  PDF Download: 1220

Review Article

Legionella Pneumophila and Dendrimers-Mediated Antisense Therapy

Roghiyeh Pashaei-Asl 1,2,3, Khodadad Khodadadi 4, Fatima Pashaei-Asl 5, Gholamreza Haqshenas 6, Nasser Ahmadian 7, Maryam Pashaiasl 8,9*, Reza Hajihosseini Baghdadabadi 1*

1 Department of Biology, Payame Noor University, Tehran, Iran.
2 Department of Anatomy, Medical School, Iran University of Medical Science, Tehran, Iran.
3 Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
4 Genetic Theme, Murdoch Children's Research Institute, Royal Children's Hospital, The University of Melbourne, Melbourne, Australia.
5 Molecular Biology Laboratory, Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
6 Microbiology Department, Biomedical Discovery Institute, Monash University, Melbourne, Australia.
7 Transplantation Center, Department of Curative Affairs, Ministry of Health and Medical Education, Tehran, Iran.
8 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
9 Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
*Corresponding Authors: Email: pashaim@tbzmed.ac.ir; Email: r.hajihosseini@shargh.tpnu.ac.ir

Abstract

Finding novel and effective antibiotics for treatment of Legionella disease is a challenging field. Treatment with antibiotics usually cures Legionella infection; however, if the resultant disease is not timely recognized and treated properly, it leads to poor prognosis and high case fatality rate. Legionella pneumophila DrrA protein (Defects in Rab1 recruitment protein A)/also known as SidM affects host cell vesicular trafficking through modification of the activity of cellular small guanosine triphosphatase )GTPase( Rab (Ras-related in brain) function which facilitates intracellular bacterial replication within a supporter vacuole. Also, Legionella pneumophila LepA and LepB (Legionella effector protein A and B) proteins suppress host-cell Rab1 protein’s function resulting in the cell lysis and release of bacteria that subsequently infect neighbour cells. Legionella readily develops resistant to antibiotics and, therefore, new drugs with different modes of action and therapeutic strategic approaches are urgently required among antimicrobial drug therapies;gene therapy is a novel approach for Legionnaires disease treatment. On the contrary to the conventional treatment approaches that target bacterial proteins, new treatment interventions target DNA (Deoxyribonucleic acid), RNA (Ribonucleic acid) species, and different protein families or macromolecular complexes of these components. The above approaches can overcome the problems in therapy of Legionella infections caused by antibiotics resistance pathogens. Targeting Legionella genes involved in manipulating cellular vesicular trafficking using a dendrimer-mediated antisense therapy is a promising approach to inhibit bacterial replication within the target cells.
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Submitted: 26 Feb 2017
Revision: 29 Apr 2017
Accepted: 30 Apr 2017
ePublished: 30 Jun 2017
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