Pangenome Analytics Reveal Two-Component Systems as Conserved Targets in ESKAPEE Pathogens
Akanksha Rajput1, Yara Seif1, Kumari Sonal Choudhary1
1Systems Biology Research Group, Department of Bioengineering, University of California, San Diego, San Diego, California, USA.
Msystems
|January 27, 2021
Summary
Two-component systems (TCSs) are crucial for bacterial survival and virulence, particularly in ESKAPEE pathogens. Their conserved nature and essential roles make TCSs promising drug targets for combating antibiotic resistance.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Discovery
Background:
- Two-component systems (TCSs) regulate bacterial responses to environmental changes, influencing critical processes like antibiotic resistance and pathogenicity.
- The ESKAPEE group of pathogens represents a major global health threat due to healthcare-associated infections.
Purpose of the Study:
- To conduct a comprehensive pangenomic analysis of TCSs in ESKAPEE pathogens.
- To evaluate the potential of TCSs as drug targets for combating antibiotic resistance.
Main Methods:
- Annotation and pangenomic analysis of TCSs.
- Gene orientation and sequence variation analysis.
- Fitness score analysis to assess the impact of TCS mutations.
Main Results:
- TCS distribution varies between Gram-positive and Gram-negative bacteria, with notable exceptions like KdpDE.
- Most ESKAPEE pathogens exhibit closed pangenomes for TCSs, indicating their conserved nature.
- Mutations in certain TCSs were found to be potentially lethal, highlighting their essentiality.
Conclusions:
- TCSs are conserved and essential in ESKAPEE pathogens, making them attractive targets for novel antimicrobial strategies.
- Targeting TCSs offers a promising approach to overcome antibiotic resistance in critical pathogens.
Keywords:
ESKAPEE pathogensantibiotic resistancegenomic architecturepangenomic analysistwo-component systemsMore Related Videos
14:06Mapping Bacterial Functional Networks and Pathways in Escherichia Coli using Synthetic Genetic Arrays
Published on: November 12, 2012
46.8K
09:44Characterization of a Pathogenic Escherichia coli Strain Derived from Oreochromis spp. Farms Using Whole-Genome Sequencing
Published on: December 23, 2022
2.6K
Related Concept Videos
01:28Global Regulatory Systems
341
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
341
01:15Diversity of Protists I
629
Excavata is a diverse group of protists that includes both chemoorganotrophic and phototrophic species, with some thriving in anaerobic environments. Among the key groups within Excavata are diplomonads and parabasalids, which are flagellated protists that lack mitochondria and chloroplasts. These microorganisms typically inhabit anoxic environments, such as the intestines of animals, where they exist either symbiotically or as parasites, relying on fermentation for energy production. Some...
629
01:23The Antiviral System of Bacteria and Archaea: CRISPR
407
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats is a adaptive immune system found in bacteria and archaea that protects against viral infections. This system enables prokaryotic cells to identify, remember, and neutralize foreign genetic elements, primarily bacteriophages, by storing fragments of the invader’s DNA as a genetic memory.The CRISPR immune response begins during an initial infection. Cas (CRISPR-associated) proteins play a central role in this...
407
01:17Gram-negative Bacterial Protein Secretion Systems
392
Gram-negative bacteria utilize sophisticated protein secretion systems to transport proteins across their double-membrane envelope into the extracellular environment or host cells. Based on their mechanism of action, these systems are classified into one-step and two-step pathways.One-Step Secretion Systems (Types I, III, IV, and VI)One-step secretion systems bypass the periplasm entirely, forming a continuous channel that spans both the inner and outer membranes:Type I Secretion System (T1SS):...
392
02:53CRISPR and crRNAs
18.2K
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
18.2K
01:29Modern Molecular Taxonomy
373
Advancements in molecular biology have revolutionized the identification and characterization of bacteria, with multiple methods leveraging DNA sequencing for enhanced precision. As sequencing technologies improve and costs decline, these approaches are increasingly used in clinical, environmental, and evolutionary studies.Multilocus Sequence Typing (MLST) examines several housekeeping genes, essential chromosomal genes encoding cellular functions, to distinguish strains. Approximately...
373