Controlling biofilms of gram-positive pathogenic bacteria.
Many bacteria can form aggregates on interfaces, called biofilms, where they are much more protected against toxic agents such as antibiotics or antibodies. Bacteria organized in biofilms are therefore very difficult to control and often even high dosages of antibiotics cannot clear infectious biofilms. To form biofilms bacteria have to start a complex genetic program to switch from planktonic to sessile lifestyle. This starts with the determination of their cell density, a process called quorum sensing, triggered by small, water soluble molecules, so called autoinducers. From Gram-positive bacteria several small peptides are known, many of them thiolactones. More recently another group of compounds was discovered probably formed from ribose-homocysteine and the first autoinducer-II identified is a furanosyl borate diester. While small peptides are found to trigger the intraspecies communication autoinducer-II is assumed to be used for communication at the interspecies level. Taking the lead structure from these peptides several derivatives have been developed which prevent biofilm formation in many Gram-positive bacteria, including Staphylococcus aureus. Some of these compounds are already in clinical studies. In this review the different approaches to control bacterial biofilms are discussed together with the difficulties arising from the species-specificity of the autoinducers.
Abraham
Wolf-Rainer
WR
GBF -- National Research Centre for Biotechnology, Chemical Microbiology, Mascheroder Weg 1, 38124 Braunschweig, Germany. wab@gbf.de
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology*; D006714:Homoserine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014166:Transferases / Q000235:genetics / Q000378:metabolism
C095698:Agr protein, Staphylococcus aureus; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; C061262:ComA protein, Bacteria; D004268:DNA-Binding Proteins; D007783:Lactones; D008565:Membrane Proteins; C091088:N-octanoylhomoserine lactone; C428447:RAP protein, Staphylococcus aureus; D015534:Trans-Activators; C423628:competence factor, Streptococcus; D006714:Homoserine; D014166:Transferases; C064995:comP protein, Bacillus subtilis