SecA Inhibitors Block Growth of Methicillin-Resistant Staphylococcus aureus
By LabMedica International staff writers Posted on 15 Dec 2015 |

Image: Colorized scanning electron micrograph (SEM) shows a grouping of methicillin resistant Staphylococcus aureus (MRSA) bacteria magnified 20,000 times (Photo courtesy of the CDC – US Centers for Disease Control and Prevention).
A novel class of low molecular weight compounds has been shown to effectively inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA), one of the most serious drug-resistant bacterial pathogens.
Investigators at Georgia State University (Atlanta, USA) had shown previously that small molecular components of the dye Rose Bengal (RB) were active against the bacteria Escherichia coli and Bacillus subtilis. This activity was found to be due to inhibition of SecA, a cell membrane-associated subunit of the eubacterial Sec or Type II secretory pathway, a system which is responsible for the secretion of proteins through the cell membrane. Within this system SecA has the functional properties of an ATPase and is required to empower the movement of the protein substrate across the translocation channel. Thus, SecA is a key component of the general bacterial secretion system required for viability and virulence.
In the current study, which was published in the November 1, 2015, issue of the journal Bioorganic & Medicinal Chemistry, the investigators evaluated two potent RB analogs for activities against MRSA strains and for their mechanism of actions.
These analogs inhibited the ATPase activities of S. aureus SecA1 (SaSecA1) and SecA2 (SaSecA2), and inhibited the SaSecA1-dependent protein-conducting channel. Moreover, these inhibitors reduced the secretion of three toxins from S. aureus and exerted potent bacteriostatic effects against three MRSA strains.
The best inhibitor, SCA-50, showed potent concentration-dependent bactericidal activity against MRSA Mu50 strain and very importantly, two to 60-fold more potent inhibitory effect on MRSA Mu50 than all the commonly used antibiotics including vancomycin, which is considered the last resort option in treating MRSA-related infections.
Deletion or overexpression of bacterial efflux pumps had minimal effect on the antimicrobial activities against S. aureus, indicating that the effects of SecA inhibitors were not affected by the presence of these efflux pumps. This study showed that these small molecule analogs of Rose Bengal targeted SecA functions, had potent antimicrobial activities, reduced the secretion of toxins, and had the ability to overcome the effect efflux pumps, which are responsible for multi-drug resistance.
"We have found that SecA inhibitors are broad-spectrum antimicrobials and are very effective against strains of bacteria that are resistant to existing antibiotics," said contributing author Dr. Binghe Wang, professor of chemistry at Georgia State University.
Related Links:
Georgia State University
Investigators at Georgia State University (Atlanta, USA) had shown previously that small molecular components of the dye Rose Bengal (RB) were active against the bacteria Escherichia coli and Bacillus subtilis. This activity was found to be due to inhibition of SecA, a cell membrane-associated subunit of the eubacterial Sec or Type II secretory pathway, a system which is responsible for the secretion of proteins through the cell membrane. Within this system SecA has the functional properties of an ATPase and is required to empower the movement of the protein substrate across the translocation channel. Thus, SecA is a key component of the general bacterial secretion system required for viability and virulence.
In the current study, which was published in the November 1, 2015, issue of the journal Bioorganic & Medicinal Chemistry, the investigators evaluated two potent RB analogs for activities against MRSA strains and for their mechanism of actions.
These analogs inhibited the ATPase activities of S. aureus SecA1 (SaSecA1) and SecA2 (SaSecA2), and inhibited the SaSecA1-dependent protein-conducting channel. Moreover, these inhibitors reduced the secretion of three toxins from S. aureus and exerted potent bacteriostatic effects against three MRSA strains.
The best inhibitor, SCA-50, showed potent concentration-dependent bactericidal activity against MRSA Mu50 strain and very importantly, two to 60-fold more potent inhibitory effect on MRSA Mu50 than all the commonly used antibiotics including vancomycin, which is considered the last resort option in treating MRSA-related infections.
Deletion or overexpression of bacterial efflux pumps had minimal effect on the antimicrobial activities against S. aureus, indicating that the effects of SecA inhibitors were not affected by the presence of these efflux pumps. This study showed that these small molecule analogs of Rose Bengal targeted SecA functions, had potent antimicrobial activities, reduced the secretion of toxins, and had the ability to overcome the effect efflux pumps, which are responsible for multi-drug resistance.
"We have found that SecA inhibitors are broad-spectrum antimicrobials and are very effective against strains of bacteria that are resistant to existing antibiotics," said contributing author Dr. Binghe Wang, professor of chemistry at Georgia State University.
Related Links:
Georgia State University
Latest BioResearch News
- Genome Analysis Predicts Likelihood of Neurodisability in Oxygen-Deprived Newborns
- Gene Panel Predicts Disease Progession for Patients with B-cell Lymphoma
- New Method Simplifies Preparation of Tumor Genomic DNA Libraries
- New Tool Developed for Diagnosis of Chronic HBV Infection
- Panel of Genetic Loci Accurately Predicts Risk of Developing Gout
- Disrupted TGFB Signaling Linked to Increased Cancer-Related Bacteria
- Gene Fusion Protein Proposed as Prostate Cancer Biomarker
- NIV Test to Diagnose and Monitor Vascular Complications in Diabetes
- Semen Exosome MicroRNA Proves Biomarker for Prostate Cancer
- Genetic Loci Link Plasma Lipid Levels to CVD Risk
- Newly Identified Gene Network Aids in Early Diagnosis of Autism Spectrum Disorder
- Link Confirmed between Living in Poverty and Developing Diseases
- Genomic Study Identifies Kidney Disease Loci in Type I Diabetes Patients
- Liquid Biopsy More Effective for Analyzing Tumor Drug Resistance Mutations
- New Liquid Biopsy Assay Reveals Host-Pathogen Interactions
- Method Developed for Enriching Trophoblast Population in Samples
Channels
Clinical Chemistry
view channel
Skin Swabs Could Detect Parkinson’s Years Before Symptoms Appear
Parkinson’s disease is notoriously difficult to diagnose in its early stages, as motor symptoms do not appear until later in the progression of the disease. The ability to detect the disease up to seven... Read more
New Clinical Chemistry Analyzer Designed to Meet Growing Demands of Modern Labs
A new clinical chemistry analyzer is designed to provide outstanding performance and maximum efficiency, without compromising affordability, to meet the growing demands of modern laboratories.... Read more
New Reference Measurement Procedure Standardizes Nucleic Acid Amplification Test Results
Nucleic acid amplification tests (NAATs) play a key role in diagnosing a wide range of infectious diseases. These tests are generally known for their high sensitivity and specificity, and they can be developed... Read moreMolecular Diagnostics
view channel
Highly Accurate Biomarkers Could Detect Ovarian Cancer Before Clinical Diagnosis
Ovarian cancer is a deadly and challenging disease, primarily because early detection is difficult. Most women (70-75%) are diagnosed only after the cancer has already spread, which significantly reduces... Read more
New Gene Tool to Enable Earlier Detection and Treatment of Cardiometabolic Diseases
Cardiometabolic diseases, which affect the heart, blood vessels, and the body's ability to process food and generate energy, are difficult to diagnose early due to the complex genetic changes that contribute... Read moreHematology
view channel
Disposable Cartridge-Based Test Delivers Rapid and Accurate CBC Results
Complete Blood Count (CBC) is one of the most commonly ordered lab tests, crucial for diagnosing diseases, monitoring therapies, and conducting routine health screenings. However, more than 90% of physician... Read more
First Point-of-Care Heparin Monitoring Test Provides Results in Under 15 Minutes
Heparin dosing requires careful management to avoid both bleeding and clotting complications. In high-risk situations like extracorporeal membrane oxygenation (ECMO), mortality rates can reach about 50%,... Read moreImmunology
view channel
New AI System Uncovers Hidden Cell Subtypes to Advance Cancer Immunotherapy
To produce effective targeted therapies for cancer, scientists need to isolate the genetic and phenotypic characteristics of cancer cells, both within and across different tumors. These differences significantly... Read more
Evolutionary Clinical Trial to Identify Novel Biomarker-Driven Therapies for Metastatic Breast Cancer
Metastatic breast cancer, which occurs when cancer spreads from the breast to other parts of the body, is one of the most difficult cancers to treat. Nearly 90% of patients with metastatic cancer will... Read more
Groundbreaking Lateral Flow Test Quantifies Nucleosomes in Whole Venous Blood in Minutes
Diagnosing immune disruptions quickly and accurately is crucial in conditions such as sepsis, where timely intervention is critical for patient survival. Traditional testing methods can be slow, expensive,... Read moreMicrobiology
view channel
Early Detection of Gut Microbiota Metabolite Linked to Atherosclerosis Could Revolutionize Diagnosis
Cardiovascular disease is the leading cause of death worldwide, and atherosclerosis plays a critical role in its development. This chronic condition, characterized by the hardening and narrowing of arteries... Read more
Viral Load Tests Can Help Predict Mpox Severity
Mpox is a viral infection that causes flu-like symptoms and a characteristic rash, which evolves significantly over time and varies between patients. The disease spreads mainly through direct contact with... Read more
Gut Microbiota Analysis Enables Early and Non-Invasive Detection of Gestational Diabetes
Gestational diabetes mellitus is a common metabolic disorder marked by abnormal glucose metabolism during pregnancy, typically emerging in the mid to late stages. It significantly heightens the risk of... Read morePathology
view channel
AI Tool Accurately Determines Breast Cancer Prognosis
A new study has found that cells and tissues surrounding a breast cancer tumor may hold critical information about how patients will respond to treatment. The research, published in the journal Patterns,... Read more
Powerful New Tool Improves Tissue Cancer Analysis
Studying the mix of cell types in human tissue is crucial for understanding diseases like cancer, but it presents significant challenges in both accuracy and scalability. The tumor microenvironment, composed... Read moreTechnology
view channel
Electronic Biosensors Used to Detect Pathogens Can Rapidly Detect Cancer Cells
A major challenge in healthcare is the early and affordable detection of serious diseases such as cancer. Early diagnosis remains difficult due to the complexity of identifying specific genetic markers... Read more
Safer, Portable and Low-Cost Imaging Solution to Revolutionize Biomedical Diagnostics
In diagnosing diseases and monitoring treatment, accurate and quick detection of temperature within biological tissues can be crucial, especially in early disease detection. Conventional methods such as... Read more
Multifunctional Nanomaterial Simultaneously Performs Cancer Diagnosis, Treatment, and Immune Activation
Cancer treatments, including surgery, radiation therapy, and chemotherapy, have significant limitations. These treatments not only target cancerous areas but also damage healthy tissues, causing side effects... Read moreIndustry
view channel
QuidelOrtho and BÜHLMANN Collaborate on Gastrointestinal Biomarker Tests
QuidelOrtho Corporation (San Diego, CA, USA) and BÜHLMANN Laboratories AG (Schönenbuch, Switzerland) have announced the availability of the BÜHLMANN fCAL turbo and fPELA turbo assays on QuidelOrtho's... Read more