scholarly journals In-Silico Identified New Natural Sortase A Inhibitors Disrupt S. aureus Biofilm Formation

2020 ◽  
Vol 21 (22) ◽  
pp. 8601
Author(s):  
Kishore Reddy Venkata Thappeta ◽  
Li Na Zhao ◽  
Choy Eng Nge ◽  
Sharon Crasta ◽  
Chung Yan Leong ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Natural Compound ◽  
Microbial Growth ◽  
Bacterial Pathogenesis ◽  
Bacterial Virulence ◽  
Sortase A ◽  
Compound Library ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Mammalian Toxicity

Sortase A (SrtA) is a membrane-associated enzyme that anchors surface-exposed proteins to the cell wall envelope of Gram-positive bacteria such as Staphylococcus aureus. As SrtA is essential for Gram-positive bacterial pathogenesis but dispensable for microbial growth or viability, SrtA is considered a favorable target for the enhancement of novel anti-infective drugs that aim to interfere with key bacterial virulence mechanisms, such as biofilm formation, without developing drug resistance. Here, we used virtual screening to search an in-house natural compound library and identified two natural compounds, N1287 (Skyrin) and N2576 ((4,5-dichloro-1H-pyrrol-2-yl)-[2,4-dihydroxy-3-(4-methyl-pentyl)-phenyl]-methanone) that inhibited the enzymatic activity of SrtA. These compounds also significantly reduced the growth of S. aureus but possessed moderate mammalian toxicity. Furthermore, S. aureus strains treated with these compounds exhibited reduction in adherence to host fibrinogen, as well as biofilm formation. Hence, these compounds may represent an anti-infective therapy without the side effects of antibiotics.

Covalent Sortase A Inhibitor ML346 Prevents Staphylococcus aureus Infection of Galleria mellonella

2021 ◽  
Author(s):  
Xiang-Na Guan ◽  
Tao Zhang ◽  
Teng Yang ◽  
Ze Dong ◽  
Song Yang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Galleria Mellonella ◽  
Surface Proteins ◽  
Sortase A ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Aureus Infection ◽  
Cell Wall Peptidoglycan

The housekeeping sortase A (SrtA), a membrane-associated cysteine transpeptidase, is responsible for anchoring surface proteins to the cell wall peptidoglycan in Gram-positive bacteria. This process is essential for the regulation...

Prodigiosin from an Endofungal Bacterium Serratia marcescens D1 Inhibits Biofilm Formation in Gram-Positive Bacteria

Microbiology ◽  
2021 ◽  
Vol 90 (6) ◽  
pp. 829-838
Author(s):  
D. J. Hazarika ◽  
M. Kakoti ◽  
R. Kalita ◽  
T. Gautom# ◽  
G. Goswami ◽  
...  
Keyword(s):  
Serratia Marcescens ◽  
Biofilm Formation ◽  
Gram Positive ◽  
Gram Positive Bacteria

scholarly journals An intramembrane sensory circuit monitors sortase A–mediated processing of streptococcal adhesins

2019 ◽  
Vol 12 (580) ◽  
pp. eaas9941 ◽  
Author(s):  
Jeffrey W. Hall ◽  
Bruno P. Lima ◽  
Gaetan G. Herbomel ◽  
Tata Gopinath ◽  
LeAnna McDonald ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Biofilm Formation ◽  
Response Regulator ◽  
Sortase A ◽  
Gram Positive Bacteria ◽  
Regulatory Circuit ◽  
Bacterial Adhesins ◽  
Genes Encoding ◽  
Quality Control Mechanism ◽  
Cognate Response Regulator

Bacterial adhesins mediate adhesion to substrates and biofilm formation. Adhesins of the LPXTG family are posttranslationally processed by the cell membrane–localized peptidase sortase A, which cleaves the LPXTG motif. This generates a short C-terminal peptide (C-pep) that remains in the cell membrane, whereas the mature adhesin is incorporated into the cell wall. Genes encoding adhesins of the oral bacteriumStreptococcus gordoniiwere differentially expressed depending on whether the bacteria were isolated from saliva or dental plaque and appeared to be coordinately regulated. Deletion ofsspAandsspB (sspAB), both of which encode LPXTG-containing adhesins, unexpectedly enhanced adhesion and biofilm formation. C-peps produced from a model LPXTG-containing adhesin localized to the cell membrane and bound to and inhibited the intramembrane sensor histidine kinase SGO_1180, thus preventing activation of the cognate response regulator SGO_1181. The absence of SspAB C-peps induced the expression of thescaCBAoperon encoding the lipoprotein adhesin ScaA, which was sufficient to preserve and even enhance biofilm formation. This C-pep–driven regulatory circuit also exists in pathogenic streptococci and is likely conserved among Gram-positive bacteria. This quality control mechanism ensures that the bacteria can form biofilms under diverse environmental conditions and may play a role in optimizing adhesion and biofilm formation.

Influences of graphene oxide on biofilm formation of gram-negative and gram-positive bacteria

2017 ◽  
Vol 25 (3) ◽  
pp. 2853-2860 ◽  
Author(s):  
Chao Song ◽  
Chun-Miao Yang ◽  
Xue-Fei Sun ◽  
Peng-Fei Xia ◽  
Jing Qin ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Biofilm Formation ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria

scholarly journals Novel Sortase A Inhibitors to Counteract Gram-Positive Bacterial Biofilms

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 23
Author(s):  
Maria Valeria Raimondi ◽  
Roberta Listro ◽  
Maria Grazia Cusimano ◽  
Mery La Franca ◽  
Teresa Faddetta ◽  
...  
Keyword(s):  
Cell Wall ◽  
Surface Proteins ◽  
Bacterial Biofilms ◽  
Sortase A ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Membrane Enzyme

Sortase A (SrtA) is a membrane enzyme responsible for the covalent anchoring of surface proteins on the cell wall of Gram-positive bacteria. [...]

scholarly journals Polymer Adhesin Domains in Gram-Positive Cell Surface Proteins

2020 ◽  
Vol 11 ◽  
Author(s):  
Michael A. Järvå ◽  
Helmut Hirt ◽  
Gary M. Dunny ◽  
Ronnie P.-A. Berntsson
Keyword(s):  
Protein Function ◽  
Biofilm Formation ◽  
Lipoteichoic Acid ◽  
Surface Proteins ◽  
Protein Domain ◽  
Gram Positive ◽  
Surface Attachment ◽  
Gram Positive Bacteria ◽  
Different Types ◽  
Host Cell Interactions

Surface proteins in Gram-positive bacteria are often involved in biofilm formation, host-cell interactions, and surface attachment. Here we review a protein module found in surface proteins that are often encoded on various mobile genetic elements like conjugative plasmids. This module binds to different types of polymers like DNA, lipoteichoic acid and glucans, and is here termed polymer adhesin domain. We analyze all proteins that contain a polymer adhesin domain and classify the proteins into distinct classes based on phylogenetic and protein domain analysis. Protein function and ligand binding show class specificity, information that will be useful in determining the function of the large number of so far uncharacterized proteins containing a polymer adhesin domain.

Genetic tools derived from Staphylococcus aureus for biotechnological applications in Gram-positive bacteria

2021 ◽  
Author(s):  
◽  
Pedro Dorado Morales
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Small Rnas ◽  
Infectious Agents ◽  
Biotechnological Applications ◽  
Gram Positive ◽  
Genetic Tools ◽  
Cellular Processes ◽  
Gram Positive Bacteria ◽  
Regulatory Functions

Staphylococcus aureus is a versatile human pathogen that has emerged as one of the most successful infectious agents of recent times, able to cause a range of diseases including skin and soft tissue infections, endocarditis, sepsis, pneumonia, osteomyelitis, bacteremia, and abscesses in organ tissues. Besides its clinical relevance, S. aureus has served as a model to study fundamental cellular processes, such as biofilm formation, the regulatory functions of small RNAs or growth and division of spherical cocci. Based on the accumulated knowledge of S. aureus biology, the availability of database resources and the advances in high-throughput genome sequencing, in this work we have aimed at developing new genetic tools derived from S. aureus for biotechnological applications in Gram-positive bacteria.

scholarly journals Biofilm formation and dispersal in Gram-positive bacteria

2011 ◽  
Vol 22 (2) ◽  
pp. 172-179 ◽  
Author(s):  
Tjakko Abee ◽  
Ákos T Kovács ◽  
Oscar P Kuipers ◽  
Stijn van der Veen
Keyword(s):  
Biofilm Formation ◽  
Gram Positive ◽  
Gram Positive Bacteria

Antimicrobial Activity of Some Egyptian Spice Essential Oils

1989 ◽  
Vol 52 (9) ◽  
pp. 665-667 ◽  
Author(s):  
R. S. FARAG ◽  
Z. Y. DAW ◽  
F. M. HEWEDI ◽  
G. S. A. EL-BAROTY
Keyword(s):  
Antimicrobial Activity ◽  
Essential Oils ◽  
Microbial Growth ◽  
Inhibitory Effect ◽  
Diffusion Method ◽  
Gram Positive ◽  
Filter Paper Disc ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Chemical Structures

Six spice essential oils (sage, rosemary, caraway, cumin, clove, and thyme) and their basic ingredients were tested for their inhibitory effect against 3 strains of Gram-negative bacteria, 4 strains of Gram-positive bacteria, one acid fast bacterium, and one yeast. Preliminary screening of antimicrobial activity of the essential oils was done using the filter paper disc agar diffusion method. The minimum inhibitory concentration for each essential oil against various micro-organisms was also measured. Very low concentrations (0.25 – 12 mg/ml) of the various essential oils were sufficient to prevent microbial growth. The data show that Gram-positive bacteria were more sensitive to the antimicrobial compounds in spices than Gram-negative. The inhibition zones of different microbial growth produced by various essential oils were similar to those produced by their basic compounds. Thyme and cumin oils possessed very strong antimicrobial activity compared with the other essential oils. There was a relationship between the chemical structures of the most abundant compounds in the essential oils under investigation and the antimicrobial activity.

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