cis-2-Alkenoic Acids as Promising Drugs for the Control of Biofilm Infections

Abstract

Microbes attached to surfaces and form biofilms where they are difficult to eradicate. Here they are embedded in a complex matrix of polymers and are much less sensitive against antibiotics or the immune system. This is a growing problem, especially for implants; hence, novel approaches are urgently needed to control biofilm infections. Many of these approaches interfere with the communication between the microbial cells required for biofilm formation and maintenance, a process known as quorum sensing. But microbes have also several mechanisms to disperse their own biofilms if conditions become unfavourable. Recently, it has been found that the pathogen Pseudomonas aeruginosa disperses its mature biofilms using cis-2-decenoic acid. This fatty acid belongs to a group of cis-2-alkenoic acids which are known from several bacteria and are also triggering the communication between different species. In this review the biosynthesis of these compounds, their signal transduction and their role in species-species communication are presented. Examples are discussed where cis-2-alkenoic acids have been used to eradicate biofilms and enhance the sensitivity of pathogens against antibiotics, either alone or in combination with antibiotics. Although this presents an interesting approach for the control of biofilm infections it is still in its infancy and a much broader characterization of the effects of cis-2-alkenoic acids are needed before moving to any medical application.Keywords: biofilm, quorum-sensing, diffusible signal factor (DSF), quorum-quenching, host-pathogen interaction, cis-2-alkenoic acids, antibiotics 1 Pathogens organized in biofilms are difficult to eradicateMicroorganisms can attach to surfaces where they form biofilms, microbial aggregates embedded in a complex and structured matrix of polymers [1]. In human infections they are found on many implants but also on teeth [2] or the mucosa, e. g. in the cystic fibrosis lung [3], the skin [4] or the middle ear [5]. These aggregates are structurally complex, dynamic systems with a multitude of interactions between the community members and the host [6]. Biofilm formation is a key factor for the survival of microbes but biofilms have also the ability to disperse under unfavourable conditions to colonize new niches [7]. Biofilm infections cause many deaths and high health costs worldwide, e. g. in the U. S. alone 32% of all healthcare-associated infections are urinary tract infections, 22% are surgical site infections and 14% are blood stream infections causing costs between $5000 and $34,000 per infection and summing up to more than $5 billion in added medical costs per annum [8].The main problem comes not so much from the human pathogens causing the infections but from their organization in biofilms. Biofilm are formed for the protection of the cells against hostile environmental conditions. As a consequence, biofilm infections are difficult to eradicate because of much better protection against antibiotics compared to free living cells [9]. It has been...

Unsaturated Fatty Acids Control Biofilm Formation of Staphylococcus aureus and Other Gram-Positive Bacteria

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Bioactive Compounds Produced by Hypoxylon fragiforme against Staphylococcus aureus Biofilms

“…However, using higher active chemical derivatives of ( 2 ) or ( 3 ) combined with an antibiotic could be a promising strategy to reduce specific staphylococci infections, since the bioactive compounds even in higher concentrations (1000 μg mL −1 ) did not display cytotoxicity against mammalian cells. Many studies demonstrated the efficacy of the use of quorum-quenching compounds together with antibiotics [ 41 , 42 ].…”

Cytochalasans Act as Inhibitors of Biofilm Formation of Staphylococcus aureus

“…aureus at concentrations of 64–16 μg mL −1 , with a MIC higher than 256 μg mL −1 , demonstrating the potential of this activity. Many molecular studies are necessary to discover the mechanisms of inhibition of biofilm formations, but if the cytochalasans are combined with antibiotics [47,48], this can be a promising strategy to treat staphylococcal infections.…”