The worldwide emergence of antibiotic-resistant bacteria and the thread of widespread superbug infections have led researchers to constantly look for novel effective antimicrobial agents. Within the past two decades, there has been an increase in studies attempting to discover molecules with innovative properties against pathogenic bacteria, notably by disrupting mechanisms of bacterial virulence and/or biofilm formation which are both regulated by the cell-to-cell communication mechanism called ‘quorum sensing’ (QS). Certainly, targeting the virulence of bacteria and their capacity to form biofilms, without affecting their viability, may contribute to reduce their pathogenicity, allowing sufficient time for an immune response to infection and a reduction in the use of antibiotics. African plants, through their huge biodiversity, present a considerable reservoir of secondary metabolites with a very broad spectrum of biological activities, a potential source of natural products targeting such non-microbicidal mechanisms. The present paper aims to provide an overview on two main aspects: (i) succinct presentation of bacterial virulence and biofilm formation as well as their entanglement through QS mechanisms and (ii) detailed reports on African plant extracts and isolated compounds with antivirulence properties against particular pathogenic bacteria.
Pseudomonas aeruginosa has the ability to resist almost all available antibiotics by rapidly accumulating multiple resistance mechanisms and thus lead to a therapeutic impasse and higher mortality in infected patients. The objective of this study was to assess the phenotypic variation in resistance to tobramycin and ofloxacin from Pseudomonas aeruginosa by repeated exhibition after determination of the minimum inhibitory concentration. This is a prospective and descriptive study carried out in the Laboratory of Microbiology of Fundamental and Applied Biochemistry (Faculty of Sciences, Antananarivo) during the month of January 2020. The strains studied were the virulent wild strain of Pseudomonas aeruginosa PAO1 supplied by the Laboratory and two clinical strains of Pseudomonas aeruginosa from the Microbiology Laboratory of the Joseph Ravoahangy Andrianavalona University Hospital Center, Antananarivo. The strains of P. aeruginosa were cultured in the liquid culture medium (which is Luria Bertani, added with a buffer system of 3- (N-morpholino) propanesulfonic acid (LB-MOPS) which will stabilize the pH and a solid culture medium which is Columbia agar. Repeated exhibition to Tobramycin and Ofloxacin from these strains have been made. The MIC is determined by a visual evaluation of the turbidity of the various wells of the microplate. The MIC value of Pseudomonas aeruginosa with tobramycin and ofloxacin is very variable for the initial MIC until the 5th generation after repeated exhibition. More Pseudomonas aeruginosa is exposed to an antibiotic many times, the more it develops resistance to this antibiotic, even being sensitive at the start. That is to say, clinically, the dose prescribed for the antibiotic has been greatly exceeded if Pseudomonas aeruginosa is repeatedly exposed to the same antibiotic.
Recently, the xanthophyll carotenoid lutein has been qualified as a potential quorum sensing (QS) and biofilm inhibitor against Pseudomonas aeruginosa. To address the potential of this xanthophyll compound as a relevant antivirulence agent, we investigated in depth its impact on the invasion capabilities and aggressiveness of P. aeruginosa PAO1, which rely on the bacterial ability to build and maintain protective barriers, use different types of motilities and release myriad virulence factors, leading to host cell and tissue damages. Our data, obtained on the PAO1 strain, indicate that all-trans lutein (Lut; 22 µM) disrupts biofilm formation and disorganizes established biofilm structure without affecting bacterial viability, while improving the bactericidal activity of tobramycin against biofilm-encapsulated PAO1 cells. Furthermore, this xanthophyll affects PAO1 twitching and swarming motilities while reducing the production of the extracellular virulence factors pyocyanin, elastase and rhamnolipids as well as the expression of the QS-regulated lasB and rhlA genes without inhibiting the QS-independent aceA gene. Interestingly, the expression of the QS regulators rhlR/I and lasR/I is significantly reduced as well as that of the global virulence factor regulator vfr, which is suggested to be a major target of Lut. Finally, an oxidative metabolite of Lut, 3′-dehydrolutein, induces a similar inhibition phenotype. Taken together, lutein-type compounds represent potential agents to control the invasive ability and antibiotic resistance of P. aeruginosa.
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