Biology Reference
In-Depth Information
1. INTRODUCTION
For years, scientists have been interested in the therapeutic potential
of RNA. Catalytic RNAs and small RNAs are widely studied in the hope
of developing RNA drugs that can be used to treat cancer, heart disease,
diabetes, and more. One area that is in dire need of novel therapeutics is
that of bacterial infections, particularly those caused by microbes that
have become resistant to common antibiotics frequently used to treat
infection.
The threat of bacterial infections due to a lack of effective antibiotics
has come to the forefront as pathogens have become resistant to almost
every antibiotic available to the public. A group of such pathogens are
Gram-positive bacteria including the antibiotic-resistant superbug
Staph-
ylococcus aureus
and the opportunistic bacterium
Enterococcus faecalis
,which
has intrinsic antibiotic resistance and a remarkable capacity for developing
antibiotic resistance.
1
Inadditiontosuchbacteriathathavedeveloped
antibiotic resistance, a number of other Gram-positive members also pose
a threat to human health. These bacteria include
Bacillus anthracis
,abio-
terror threat; the food-borne pathogens
Bacillus cereus
and
Listeria mono-
cytogenes
; and the causative agent of tetanus,
Clostridium tetani
.Mostof
the antibiotics used today were developed almost 50 years ago, and they
target a limited number of bacterial processes. The need is great for new
classes of antimicrobial agents that target different but specific and essen-
tial bacterial pathways. Over the past decade, scientists have identified
novel RNA elements termed riboswitches that control the metabolic
state of microorganisms by directly binding metabolites and regulating
gene expression. This group of functional RNAs could be targets for
novel antibiotic development. Structure-function studies of riboswitches
and their interactions with metabolites are expected to enable rational
design of nonnatural metabolite-like compounds that might function as
artificial agonists or antagonists, and ultimately as antibiotics. Such com-
pounds would target a biosynthetic pathway of bacterial metabolism and
perturb regulation of gene expression. This approach to affecting bacterial
growth through alteration of gene expression within essential metabolic
pathways provides a novel means by which to inhibit and potentially kill
bacteria.
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