Pseudonajide peptide derived from snake venom alters cell envelope integrity interfering on biofilm formation in Staphylococcus epidermidis

Abstract Background The increase in bacterial resistance phenotype cases is a global health problem. New strategies must be explored by the scientific community in order to create new treatment alternatives. Animal venoms are a good source for antimicrobial peptides (AMPs), which are excellent candidates for new antimicrobial drug development. Cathelicidin-related antimicrobial peptides (CRAMPs) from snake venoms have been studied as a model for the design of new antimicrobial pharmaceuticals against bacterial infections. Results In this study we present an 11 amino acid-long peptide, named pseudonajide, which is derived from a Pseudonaja textilis venom peptide and has antimicrobial and antibiofilm activity against Staphylococcus epidermidis . Pseudonajide was selected based on the sequence alignments of various snake venom peptides that displayed activity against bacteria. Antibiofilm activity assays with pseudonajide concentrations ranging from 3.12 to 100 µM showed that the lowest concentration to inhibit biofilm formation was 25 µM. Microscopy analysis demonstrated that pseudonajide interacts with the bacterial cell envelope, disrupting the cell walls and membranes, leading to morphological defects in prokaryotes. Conclusions Our results suggest that pseudonajide’s positives charges interact with negatively charged cell wall components of S. epidermidis, leading to cell damage and inhibiting biofilm formation.

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Pseudonajide peptide derived from snake venom alters cell envelope integrity interfering on biofilm formation in Staphylococcus epidermidis

10.21203/rs.2.17309/v4 ◽

2020 ◽

Author(s):

Rafael Schneider ◽

Muriel Primon-Barros ◽

Rafael Gomes Von Borowski ◽

Sophie Chat ◽

Sylvie Nonin-Lecomte ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Snake Venom ◽

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Cell Damage ◽

Cell Envelope ◽

Antibiofilm Activity ◽

Sequence Alignments

Abstract Background The increase in bacterial resistance phenotype cases is a global health problem. New strategies must be explored by the scientific community in order to create new treatment alternatives. Animal venoms are a good source for antimicrobial peptides (AMPs), which are excellent candidates for new antimicrobial drug development. Cathelicidin-related antimicrobial peptides (CRAMPs) from snake venoms have been studied as a model for the design of new antimicrobial pharmaceuticals against bacterial infections. Results In this study we present an 11 amino acid-long peptide, named pseudonajide, which is derived from a Pseudonaja textilis venom peptide and has antimicrobial and antibiofilm activity against Staphylococcus epidermidis . Pseudonajide was selected based on the sequence alignments of various snake venom peptides that displayed activity against bacteria. Antibiofilm activity assays with pseudonajide concentrations ranging from 3.12 to 100 µM showed that the lowest concentration to inhibit biofilm formation was 25 µM. Microscopy analysis demonstrated that pseudonajide interacts with the bacterial cell envelope, disrupting the cell walls and membranes, leading to morphological defects in prokaryotes. Conclusions Our results suggest that pseudonajide’s positives charges interact with negatively charged cell wall components of S. epidermidis, leading to cell damage and inhibiting biofilm formation.

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Pseudonajide is an antibiotic peptide derived from snake venom that alter cell wall and membrane integrity interfering on biofilm formation.

10.21203/rs.2.17309/v1 ◽

2019 ◽

Author(s):

Rafael Schneider ◽

Muriel Primon-Barros ◽

Rafael Gomes Von Borowski ◽

Sophie Chat ◽

Reynald Gillet ◽

...

Keyword(s):

Cell Wall ◽

Snake Venom ◽

Biofilm Formation ◽

Bacterial Resistance ◽

Cell Damage ◽

Cell Envelope ◽

Membrane Integrity ◽

Antibiofilm Activity ◽

Sequence Alignments ◽

Resistance Phenotype

Abstract Background The increase of bacterial resistance phenotype cases is a global health problem. New strategies in scientific community must be explored in order to create new treatment alternatives. Animal venoms are a good source for antimicrobial peptides (AMPs), which are excellent candidates for new antimicrobial drug development. These molecules have highly diverse targets in prokaryotic cells, making resistance phenotype development more difficult. Results In this study we present a peptide of just 11 amino acids which has antimicrobial and antibiofilm activity against Staphyloccocus epidermidis. Named pseudonajide, it is derived from Pseudonaja textilis venom. Pseudonajide was selected based on the sequence alignments of various snake venom peptides that displayed activity against bacteria. Several concentrations of pseudonajide were tested in antibiofilm activity essay, it was detected that 25 µM was the best minimal concentration for biofilm inhibiting activity. Microscopy analysis demonstrates that pseudonajide interacts with the bacterial cell envelope, disrupting the cell wall and membrane leading to morphological defects in prokaryotes. Conclusions Our results suggest that pseudonajide’s positives charges interacts with negative charged cell wall components of S. epidermidis. Leading to cell damage and biofilm formation inhibition.

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Transporters and Efflux Pumps Are the Main Mechanisms Involved in Staphylococcus epidermidis Adaptation and Tolerance to Didecyldimethylammonium Chloride

Microorganisms ◽

10.3390/microorganisms8030344 ◽

2020 ◽

Vol 8 (3) ◽

pp. 344 ◽

Cited By ~ 1

Author(s):

Urška Ribič ◽

Jernej Jakše ◽

Nataša Toplak ◽

Simon Koren ◽

Minka Kovač ◽

...

Keyword(s):

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Efflux Pump ◽

Thioredoxin Reductase ◽

Multidrug Transporter ◽

Acid Biosynthesis ◽

Tolerance Mechanisms ◽

Down Regulation ◽

Didecyldimethylammonium Chloride ◽

First Time

Staphylococcus epidermidis cleanroom strains are often exposed to sub-inhibitory concentrations of disinfectants, including didecyldimethylammonium chloride (DDAC). Consequently, they can adapt or even become tolerant to them. RNA-sequencing was used to investigate adaptation and tolerance mechanisms of S. epidermidis cleanroom strains (SE11, SE18), with S. epidermidis SE11Ad adapted and S. epidermidis SE18To tolerant to DDAC. Adaptation to DDAC was identified with up-regulation of genes mainly involved in transport (thioredoxin reductase [pstS], the arsenic efflux pump [gene ID, SE0334], sugar phosphate antiporter [uhpT]), while down-regulation was seen for the Agr system (agrA, arC, agrD, psm, SE1543), for enhanced biofilm formation. Tolerance to DDAC revealed the up-regulation of genes associated with transporters (L-cysteine transport [tcyB]; uracil permease [SE0875]; multidrug transporter [lmrP]; arsenic efflux pump [arsB]); the down-regulation of genes involved in amino-acid biosynthesis (lysine [dapE]; histidine [hisA]; methionine [metC]), and an enzyme involved in peptidoglycan, and therefore cell wall modifications (alanine racemase [SE1079]). We show for the first time the differentially expressed genes in DDAC-adapted and DDAC-tolerant S. epidermidis strains, which highlight the complexity of the responses through the involvement of different mechanisms.

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A Single B-Repeat of Staphylococcus epidermidis Accumulation-Associated Protein Induces Protective Immune Responses in an Experimental Biomaterial-Associated Infection Mouse Model

Clinical and Vaccine Immunology ◽

10.1128/cvi.00306-14 ◽

2014 ◽

Vol 21 (9) ◽

pp. 1206-1214 ◽

Cited By ~ 12

Author(s):

Lin Yan ◽

Lei Zhang ◽

Hongyan Ma ◽

David Chiu ◽

James D. Bryers

Keyword(s):

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Porous Scaffold ◽

The United States ◽

Protein Vaccine ◽

Weight Changes ◽

Biofilm Inhibition ◽

Content Type ◽

Accumulation Associated Protein

ABSTRACTNosocomial infections are the fourth leading cause of morbidity and mortality in the United States, resulting in 2 million infections and ∼100,000 deaths each year. More than 60% of these infections are associated with some type of biomedical device.Staphylococcus epidermidisis a commensal bacterium of the human skin and is the most common nosocomial pathogen infecting implanted medical devices, especially those in the cardiovasculature.S. epidermidisantibiotic resistance and biofilm formation on inert surfaces make these infections hard to treat. Accumulation-associated protein (Aap), a cell wall-anchored protein ofS. epidermidis, is considered one of the most important proteins involved in the formation ofS. epidermidisbiofilm. A small recombinant protein vaccine comprising a single B-repeat domain (Brpt1.0) ofS. epidermidisRP62A Aap was developed, and the vaccine's efficacy was evaluatedin vitrowith a biofilm inhibition assay andin vivoin a murine model of biomaterial-associated infection. A high IgG antibody response againstS. epidermidisRP62A was detected in the sera of the mice after two subcutaneous immunizations with Brpt1.0 coadministered with Freund's adjuvant. Sera from Brpt1.0-immunized mice inhibitedin vitroS. epidermidisRP62A biofilm formation in a dose-dependent pattern. After receiving two immunizations, each mouse was surgically implanted with a porous scaffold disk containing 5 × 106CFU ofS. epidermidisRP62A. Weight changes, inflammatory markers, and histological assay results after challenge withS. epidermidisindicated that the mice immunized with Brpt1.0 exhibited significantly higher resistance toS. epidermidisRP62A implant infection than the control mice. Day 8 postchallenge, there was a significantly lower number of bacteria in scaffold sections and surrounding tissues and a lower residual inflammatory response to the infected scaffold disks for the Brpt1.0-immunized mice than for of the ovalbumin (Ova)-immunized mice.

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SCCmec-associated psm-mec mRNA promotes Staphylococcus epidermidis biofilm formation

Antonie van Leeuwenhoek ◽

10.1007/s10482-016-0741-2 ◽

2016 ◽

Vol 109 (10) ◽

pp. 1403-1415

Author(s):

Yongchang Yang ◽

Xuemei Zhang ◽

Wenfang Huang ◽

Yibing Yin

Keyword(s):

Staphylococcus Epidermidis ◽

Biofilm Formation

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Anaerobic Conditions Induce Expression of Polysaccharide Intercellular Adhesin in Staphylococcus aureus and Staphylococcus epidermidis

Infection and Immunity ◽

10.1128/iai.69.6.4079-4085.2001 ◽

2001 ◽

Vol 69 (6) ◽

pp. 4079-4085 ◽

Cited By ~ 222

Author(s):

Sarah E. Cramton ◽

Martina Ulrich ◽

Friedrich Götz ◽

Gerd Döring

Keyword(s):

Staphylococcus Aureus ◽

Staphylococcus Epidermidis ◽

Biofilm Formation ◽

Extracellular Polysaccharide ◽

Growth Conditions ◽

Anaerobic Conditions ◽

Anaerobic Environment ◽

Specific Mrna

ABSTRACT Products of the intercellular adhesion (ica) operon in Staphylococcus aureus and Staphylococcus epidermidis synthesize a linear β-1,6-linked glucosaminylglycan. This extracellular polysaccharide mediates bacterial cell-cell adhesion and is required for biofilm formation, which is thought to increase the virulence of both pathogens in association with prosthetic biomedical implants. The environmental signal(s) that triggers ica gene product and polysaccharide expression is unknown. Here we demonstrate that anaerobic in vitro growth conditions lead to increased polysaccharide expression in both S. aureus and S. epidermidis, although the regulation is less stringent inS. epidermidis. Anaerobiosis also dramatically stimulates ica-specific mRNA expression inica- and polysaccharide-positive strains of both S. aureus and S. epidermidis.These data suggest a mechanism whereby ica gene expression and polysaccharide production may act as a virulence factor in an anaerobic environment in vivo.

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Part 2: Effectiveness of a novel gentamicinpalmitate coating on biofilm formation of Staphylococcus aureus and Staphylococcus epidermidis

International Journal of Nano and Biomaterials ◽

10.1504/ijnbm.2010.036111 ◽

2010 ◽

Vol 3 (1) ◽

pp. 107 ◽

Cited By ~ 5

Author(s):

Klaus Dieter Kuhn ◽

Jorg Brunke

Keyword(s):

Staphylococcus Aureus ◽

Staphylococcus Epidermidis ◽

Biofilm Formation

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Lon Protease Has Multifaceted Biological Functions inAcinetobacter baumannii

Journal of Bacteriology ◽

10.1128/jb.00536-18 ◽

2018 ◽

Vol 201 (2) ◽

Cited By ~ 5

Author(s):

Carly Ching ◽

Brendan Yang ◽

Chineme Onwubueke ◽

David Lazinski ◽

Andrew Camilli ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Biofilm Formation ◽

Developmental Process ◽

Cell Envelope ◽

Opportunistic Pathogen ◽

Lon Protease ◽

Content Type ◽

Hospital Acquired Infections ◽

Biofilm Development ◽

Hospital Acquired

ABSTRACTAcinetobacter baumanniiis a Gram-negative opportunistic pathogen that is known to survive harsh environmental conditions and is a leading cause of hospital-acquired infections. Specifically, multicellular communities (known as biofilms) ofA. baumanniican withstand desiccation and survive on hospital surfaces and equipment. Biofilms are bacteria embedded in a self-produced extracellular matrix composed of proteins, sugars, and/or DNA. Bacteria in a biofilm are protected from environmental stresses, including antibiotics, which provides the bacteria with selective advantage for survival. Although some gene products are known to play roles in this developmental process inA. baumannii, mechanisms and signaling remain mostly unknown. Here, we find that Lon protease inA. baumanniiaffects biofilm development and has other important physiological roles, including motility and the cell envelope. Lon proteases are found in all domains of life, participating in regulatory processes and maintaining cellular homeostasis. These data reveal the importance of Lon protease in influencing keyA. baumanniiprocesses to survive stress and to maintain viability.IMPORTANCEAcinetobacter baumanniiis an opportunistic pathogen and is a leading cause of hospital-acquired infections.A. baumanniiis difficult to eradicate and to manage, because this bacterium is known to robustly survive desiccation and to quickly gain antibiotic resistance. We sought to investigate biofilm formation inA. baumannii, since much remains unknown about biofilm formation in this bacterium. Biofilms, which are multicellular communities of bacteria, are surface attached and difficult to eliminate from hospital equipment and implanted devices. Our research identifies multifaceted physiological roles for the conserved bacterial protease Lon inA. baumannii. These roles include biofilm formation, motility, and viability. This work broadly affects and expands understanding of the biology ofA. baumannii, which will permit us to find effective ways to eliminate the bacterium.

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