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Identification of the Extracytoplasmic Function σ Factor σP Regulon in Bacillus thuringiensis
Theresa D Ho1, Kelsie M Nauta1, Emma K Luhmann1
1Department of Microbiology and Immunology, Carver College of Medicine, University of Iowagrid.214572.7, Iowa City, Iowa, USA.
Msphere
|January 26, 2022
Summary
Bacillus thuringiensis uses a regulatory system, sigma P, to control multiple genes that confer resistance to beta-lactam antibiotics. This helps environmental bacteria develop new antibiotic resistance mechanisms.
Area of Science:
- Microbiology
- Molecular Biology
- Antimicrobial Resistance
Background:
- Bacillus thuringiensis and Bacillus cereus group bacteria exhibit resistance to beta-lactam antibiotics.
- This resistance is mediated by the extracytoplasmic function sigma factor, sigma P.
- Understanding resistance mechanisms in environmental bacteria is crucial for public health due to potential pathogen acquisition.
Purpose of the Study:
- To identify proteins regulated by sigma P in Bacillus thuringiensis.
- To elucidate the role of sigma P-regulated genes in beta-lactam resistance.
- To investigate the contribution of specific beta-lactamases and penicillin-binding proteins to resistance.
Main Methods:
- Label-free quantitative proteomics to compare protein expression in strains with and without sigma P.
- Transcriptional reporters to confirm gene induction by beta-lactams.
- Gene deletion studies (individual and combinatorial) to assess roles in antibiotic resistance.
Main Results:
- Identified eight members of the sigma P regulon, including four beta-lactamases and three penicillin-binding proteins (PBPs).
- Confirmed beta-lactam induction of these genes in a sigma P-dependent manner.
- Demonstrated that combinations of beta-lactamases and PBPs confer resistance to various beta-lactams, with some genes showing partial redundancy.
Conclusions:
- Bacillus thuringiensis employs a coordinated system of enzymes, regulated by sigma P, to resist beta-lactam antibiotics.
- The sigma P regulon provides broad-spectrum resistance through multiple, partially redundant genes.
- This study offers insights into antibiotic resistance mechanisms potentially transferable to pathogens.
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