Small molecule control of bacterial biofilms.
Summary of "Small molecule control of bacterial biofilms."
Bacterial biofilms are defined as a surface attached community of bacteria embedded in a matrix of extracellular polymeric substances that they have produced. When in the biofilm state, bacteria are more resistant to antibiotics and the host immune response than are their planktonic counterparts. Biofilms are increasingly recognized as being significant in human disease, accounting for 80% of bacterial infections in the body and diseases associated with bacterial biofilms include: lung infections of cystic fibrosis patients, colitis, urethritis, conjunctivitis, otitis, endocarditis and periodontitis. Additionally, biofilm infections of indwelling medical devices are of particular concern, as once the device is colonized infection is virtually impossible to eradicate. Given the prominence of biofilms in infectious diseases, there has been an increased effort toward the development of small molecules that will modulate bacterial biofilm development and maintenance. In this review, we highlight the development of small molecules that inhibit and/or disperse bacterial biofilms through non-microbicidal mechanisms. The review discuses the numerous approaches that have been applied to the discovery of lead small molecules that mediate biofilm development. These approaches are grouped into: (1) the identification and development of small molecules that target one of the bacterial signaling pathways involved in biofilm regulation, (2) chemical library screening for compounds with anti-biofilm activity, and (3) the identification of natural products that possess anti-biofilm activity, and the chemical manipulation of these natural products to obtain analogues with increased activity.
Affiliation
Department of Chemistry, North Carolina State University, Raleigh, NC 27695, USA. Christian_melander@ncsu.edu.
Journal Details
This article was published in the following journal.
Name: Organic & biomolecular chemistry
ISSN: 1477-0539
Pages: 7457-74
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22733439
- DOI: http://dx.doi.org/10.1039/c2ob25835h
Medical and Biotech [MESH] Definitions
Riboswitch
Part of a MESSENGER RNA molecule that undergoes a conformation change upon binding a specific metabolite or other small molecule thereby regulating the messenger RNA's transcription, post-transcriptional processing, transport, translation, or stability in response to varying levels of the metabolite or other small molecule.
Adhesins, Bacterial
Cell-surface components or appendages of bacteria that facilitate adhesion (BACTERIAL ADHESION) to other cells or to inanimate surfaces. Most fimbriae (FIMBRIAE, BACTERIAL) of gram-negative bacteria function as adhesins, but in many cases it is a minor subunit protein at the tip of the fimbriae that is the actual adhesin. In gram-positive bacteria, a protein or polysaccharide surface layer serves as the specific adhesin. What is sometimes called polymeric adhesin (BIOFILMS) is distinct from protein adhesin.
Biofilms
Encrustations, formed from microbes (bacteria, algae, fungi, plankton, or protozoa) embedding in extracellular polymers, that adhere to surfaces such as teeth (DENTAL DEPOSITS); PROSTHESES AND IMPLANTS; and catheters. Biofilms are prevented from forming by treating surfaces with DENTIFRICES; DISINFECTANTS; ANTI-INFECTIVE AGENTS; and antifouling agents.
Ligands
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Ribosome Subunits, Small, Bacterial
The small subunit of eubacterial RIBOSOMES. It is composed of the 16S RIBOSOMAL RNA and about 23 different RIBOSOMAL PROTEINS.
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