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.
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.