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Cell and Gene Therapy 2018 & Clinical Microbiology Congress 2018
Biomedical Research
|
ISSN: 0976-1683
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Volume 29
S e p t e m b e r 1 0 - 1 1 , 2 0 1 8 | D u b l i n , I r e l a n d
allied
academies
Joint Event on
CLINICAL AND MEDICAL MICROBIOLOGY
CELL AND GENE THERAPY
&
World Congress on
International Conference on
Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C3-008
TARGETING BACTERIAL VIRULENCE TO DEVELOP EVOLUTION PROOF
ANTIBIOTICS
Veerendra Koppolu
AstraZeneca/MedImmune, USA
K
eeping the antibiotic resistance in mind, it is of greatest need to develop new ways to treat bacterial infections. Evolution-
proof antibiotics that disarm the bacterial pathogens without impacting their survival would be an important strategy towards
sidestepping the evolution of resistance. Drugs that disarm the pathogen will generate much weaker selection for resistance than
traditional antibiotics. Disarming the pathogens is possible by targeting a family of bacterial proteins called AraC family proteins
that regulate the bacteria’s ability to infect or damage a host, rather than its ability to survive. We tested this exciting hypothesis
against Shigella flexneri, a diarrhea causing bacterial pathogen responsible for causing 165 million cases of illness and more
than 1.1 million deaths worldwide. We successfully identified several molecules that selectively inhibited an important Shigella
protein VirF that is crucial for causing infection. The highly potent molecule SE-1 is found to not impact the growth of the bacteria
but prevent bacteria’s ability to invade and infect cultured human intestinal cells. SE-1 also inhibits infection pathways in other
pathogenic bacteria that cause infections such as diarrhea, pneumonia, and cholera and thus can be developed as a novel agent
to treat multiple infections. Targeting such infection pathways may yield non-traditional antibiotics that are more powerful and
versatile than our current antimicrobials and would solve the antibiotic resistance issue that has grown to alarming levels.