AAC–June’11, Part 2

Synergistic Effect of 14-Alpha-Lipoyl Andrographolide and Various Antibiotics on the Formation of Biofilms and Production of Exopolysaccharide and Pyocyanin by Pseudomonas aeruginosa (doi:10.1128/AAC.00575-10)

Yet another related study on P. aerugenosa was presented by researchers from Jinan University College of Pharmacy and Chinese Academy of Sciences from china and University of Adelaide, Australia.

The authors have synthesized a small molecule, 14-alpha-lipoyl andrographolide (AL-1) which is a derivative of a natural product andrographolide, a diterpenoid lactore from the herb Andrographis paniculata. The later is a traditional medicine used to treat symptoms of inflammation, fever and pain due to infections since 30 years in china. The authors write about the QS system, the Pseudomonas quinolone signal (PQS) system and the Type III secretion (T3SS) system which play role in biofilm formation and pathogenesis and quote that compounds that inhibit the above systems may offer a great advantage

over conventional antimicrobials.

The authors expects the AL-1 could inhibit one or more of the above systems and could promote the antimicrobial activity of conventional antimicrobials. The selection of antibiotics to investigate the above hypothesis are potassium dehydroandropgrapholide succinate, fosfomycin, streptomycin, azithromycin, erythromycin, gentamicin and ciprofloxacin.

P. aerugenosa biofilms were studied upon treatment with the above antibiotics and AL-1 separately and in combinations. The data demonstrated that AL-1 has synergistic effects on antibiofilm and antivirulence factors activities when combined with antibiotics. Also the authors claim that AL-1 was identified as a potential inhibitor for the QS and T3SS systems (unpublished data). AL-1 also decreases EPS and pyocyanin production which could potentially contribute to the biofilm inhibition. So, the activity another candidate is proposed and demonstrated for the combination therapy with antibiotics against the biofilm infections.

A New Small Molecule Specifically Inhibits the Cariogenic Bacterium Streptococcus mutans in Multispecies Biofilms (doi:10.1128/AAC.01496-10)

A small molecule screen specific to S. mutans biofilm was performed and 8 compounds were identified out from a library of 506, by the researchers at the UAB School of Dentistry, Birmingham and North Carolina State University, Raleigh.

The aim as proposed by the authors was to find specific inhibitors for S. mutans biofilm in order to avoid disturbing the commensal residents in the oral cavity. To achieve this goal, the group designed derivatives of marine natural products based primarily on the 2-aminoimodazole scaffold.

The 8 compounds were assessed for their specificity towards S. mutans, S. sanguinis and S. gordonii in pure cultures and co-cultures. The results provides convincing evidence that the compounds are specific to S. mutans even in co-cultures.

Further the expression of important biofilm associated genes were quantified against the most active compound among by q-RT-PCR both in planktonic and biofilm cells. The compound was shown to downregulate 6 biofilm associated genes in the planktonic cells and 3 genes in the biofilm cells. Western analysis shows that the compound inhibited two key adhesins of S. mutans there by preventing the cells at the initial stage of adhesion. However there was no alterations were observed in S. sanguinis and S. gordonii.

The study proves that the compounds are verymuch specific to S. mutans when comparing to the two other strains under investigation. But the the question remain open for the other oral residents.

Two more studies on the antifungal agents targeting fungal biofilms were published in the same issue. In one of the studies (doi:10.1128/AAC.01569-10), the activities of anifulafungin and other antifungal agents were tested against different clinically relevant fungal biofilms and explored the potential for these drugs to be used in the antifungal therapy.
The other group (doi:10.1128/AAC.01601-10) tested gentian violet (GV), a triphenylmethane dye against candida and non-candida oral biofilms usually observed in HIV patients. The authors have showed both antibiofilm and antigermination activity for the GV, thus proposed as a potential candidate for clinical studies towards the treatment of candidiasis.