The cyclic peptide labaditin does not alter the outer membrane integrity of Salmonella enterica serovar Typhimurium

Abstract

Antimicrobial peptides are a promising class of new antibiotics with the ability to kill bacteria by disrupting their cell membrane, which is especially difficult for Gram-negative bacteria whose cell wall contains an outer layer of lipopolysaccharides (LPS). Here we show that the cyclic decapeptide Labaditin (Lo), with proven activity against the Gram-positive Staphylococcus aureus and Streptococcus mutans, is not able to kill the Gram-negative Salmonella enterica serovar Typhimurium (S.e.s. Typhimurium). We found that Lo induced significant changes in the surface pressure isotherms of Langmuir monolayers representing the Salmonella enterica serovar Typhimurium inner membrane (S.e.s. Typhimurium IM), and caused leakage in large unilamellar vesicles made with this IM lipid composition. On the basis of these results one should expect bactericidal activity against S.e.s. Typhimurium. However, Lo could not interact with a monolayer of LPS, causing no significant changes in either the surface pressure isotherms or in the polarization-modulated infrared reflection absorption spectra (PM-IRRAS). Therefore, the failure of Lo to kill S.e.s. Typhimurium is associated with the lack of interaction with LPS from the outer bacteria membrane. Our approach with distinct monolayer compositions and combined techniques to investigate molecular-level interactions is useful for drug design to fight antibiotic-resistant bacteria.

Peptide Extracts from Native Lactic Acid Bacteria Generate Ghost Cells and Spheroplasts upon Interaction with Salmonella enterica, as Promising Food Antimicrobials

“…The contamination of food by microorganisms is an overarching problem of the food industry. Salmonellosis causes great harm to the livestock and poultry industries; thus, its effective prevention and control are of great importance to animal husbandry and public health [ 1 ]. Efforts to reduce the bacterial growth and the associated diseases along with the expanding bacterial resistance have stimulated research to search for novel antimicrobial agents and related technologies.…”

Recent advances in the use of Langmuir monolayers as cell membrane models

“…Some classes of peptides are promising for killing bacteria, especially as they can disrupt bacteria membrane. This has motivated a number of studies with Langmuir monolayers 51 , including those from Prof. João Ruggiero 52 . In the latter study, the interaction of peptides was studied with Langmuir monolayers of DPPC, which was used to verify the influence of a peptide on lipid packing during the LE-LC coexistence plateau.…”

“…In spite of the simplifications in the modeling, these monolayers are useful to obtain molecular-level information, which is virtually impossible with any other method. One may, for instance, identify the reasons why a peptide is effective against grampositive bacteria, but not for gram-negative bacteria by simply verifying that the peptide cannot disrupt a Langmuir monolayer of lipopolysaccharide 51 . With the in situ vibrational spectroscopy techniques, on the other hand, it is possible to determine the chemical groups involved in the interactions between biologically-relevant molecules and the model membranes.…”

Role of Toluidine Blue-O Binding Mechanism for Photooxidation in Bioinspired Bacterial Membranes

“…Therefore, suitable methods are required not only to mimic the bacterial lipid membrane but also to provide information at the molecular level. In this context, Langmuir monolayers have been proven efficient models of both Gram-positive and Gram-negative bacteria membranes owing to the control of lateral packing and membrane composition. − For instance, the mechanisms of action of antimicrobial peptides have been successfully accessed on Langmuir models of S. aureus, Streptococcus mutan, , Salmonella enterica serovar Typhimurium, and E.…”

“…In this context, Langmuir monolayers have been proven efficient models of both Grampositive 28 and Gram-negative 29 bacteria membranes owing to the control of lateral packing and membrane composition. 30−35 For instance, the mechanisms of action of antimicrobial peptides have been successfully accessed on Langmuir models of S. aureus, 28 Streptococcus mutan, 36,37 Salmonella enterica serovar Typhimurium, 29 and E. coli. 38 In this study, Langmuir monolayers of 1,2-dioleoyl-snglycero-3-phosphoethanolamine (DOPE) and 1,2-dioleoyl-snglycero-3-phospho-(1′-rac-glycerol) (DOPG) were employed as simplified models of bacterial membrane to unravel the TBO binding mechanism and the effects from lipid photooxidation.…”