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Comparative Study on Antistaphylococcal Activity of Lipopeptides in Various Culture Media.

ABSTRACT: Staphylococcus aureus bacteria are one of the leading microorganisms responsible for nosocomial infections as well as being the primary causative pathogen of skin and wound infections. Currently, the therapy of staphylococcal diseases faces many difficulties, due to a variety of mechanisms of resistance and virulence factors. Moreover, a number of infections caused by S. aureus are connected with biofilm formation that impairs effectiveness of the therapy. Short cationic lipopeptides that are designed on the basis of the structure of antimicrobial peptides are likely to provide a promising alternative to conventional antibiotics. Many research groups have proved a high antistaphylococcal potential of lipopeptides, however, the use of different protocols for determination of antimicrobial activity may be the reason for inconsistency of the results. The aim of this study was to learn how the use of various bacteriological media as well as solvents may affect activity of lipopeptides and their cyclic analogs. Obtained results showed a great impact of these variables. For example, cyclic analogs were more effective when dissolved in an aqueous solution of acetic acid and bovine serum albumin (BSA). The greater activity against planktonic cultures was found in brain-heart infusion broth (BHI) and tryptic-soy broth (TSB), while the antibiofilm activity was higher in the Mueller-Hinton medium.

SUBMITTER: Jaskiewicz M

PROVIDER: S-EPMC5617979 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:UnlabelledPlant-derived compounds and other natural substances are a rich potential source of compounds that kill or attenuate pathogens that are resistant to current antibiotics. Medieval societies used a range of these natural substances to treat conditions clearly recognizable to the modern eye as microbial infections, and there has been much debate over the likely efficacy of these treatments. Our interdisciplinary team, comprising researchers from both sciences and humanities, identified and reconstructed a potential remedy for Staphylococcus aureus infection from a 10th century Anglo-Saxon leechbook. The remedy repeatedly killed established S. aureus biofilms in an in vitro model of soft tissue infection and killed methicillin-resistant S. aureus (MRSA) in a mouse chronic wound model. While the remedy contained several ingredients that are individually known to have some antibacterial activity, full efficacy required the combined action of several ingredients, highlighting the scholarship of premodern doctors and the potential of ancient texts as a source of new antimicrobial agents.ImportanceWhile the antibiotic potential of some materials used in historical medicine has been demonstrated, empirical tests of entire remedies are scarce. This is an important omission, because the efficacy of "ancientbiotics" could rely on the combined activity of their various ingredients. This would lead us to underestimate their efficacy and, by extension, the scholarship of premodern doctors. It could also help us to understand why some natural compounds that show antibacterial promise in the laboratory fail to yield positive results in clinical trials. We have reconstructed a 1,000-year-old remedy which kills the bacteria it was designed to treat and have shown that this activity relies on the combined activity of several antimicrobial ingredients. Our results highlight (i) the scholarship and rational methodology of premodern medical professionals and (ii) the untapped potential of premodern remedies for yielding novel therapeutics at a time when new antibiotics are desperately needed.

Project description:PrfA activity was studied in L. monocytogenes strain EGD and in an isogenic prfA deletion mutant (EGDΔprfA) carrying multiple copies of the wild-type prfA or the mutant prfA* gene (strains EGDΔprfApPrfA and EGDΔprfApPrfA*) after growth in brain heart infusion (BHI), Luria-Bertani broth (LB) or a defined minimal medium (MM) supplemented either with one of the three PTS-carbohydrates, glucose, mannose and cellobiose, or the non-PTS carbon source glycerol. Low PrfA activity was observed in the wild-type EGD strain in BHI and LB with either of these carbon sources, while PrfA activity was high in minimal medium in presence of glycerol but significantly reduced in presence of cellobiose. The strains expressing the prfA and prfA* gene under the prfA promoters, P1 and P2, produced equally large amounts of PrfA protein and high PrfA activity was observed in strain EGDΔprfApPrfA* under all growth conditions. In contrast, high PrfA activity in strain EGDΔprfApPrfA was only observed when this strain was cultured in BHI but not in LB or MM (in presence of either carbon source). A ptsH mutant (lacking a functional HPr) was able to grow in BHI suggesting that growth of L. monocytogenes in this culture medium is supported by carbon sources whose uptake and metabolism are independent of the PTS pathway. However, this mutant was unable to grow in LB and MM regardless which of the four carbon sources was added, suggesting that uptake of the used carbohydrates and the catabolism of glycerol depend fully on the functional common PTS pathway. Furthermore, the growth rates of L. monocytogenes are strongly reduced in presence of large amounts of PrfA protein when growing MM but less in LB and only slightly in BHI. The expression profiles of the genes encoding PTS permeases were determined in the three strains under various growth conditions. The data suggest that PrfA activity correlates with the expression level and the phosphorylation state of specific PTS permeases. This SuperSeries is composed of the SubSeries listed below.

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Comparative Study on Antistaphylococcal Activity of Lipopeptides in Various Culture Media.

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