Journal article
Identification of the Extracytoplasmic Function sigma Factor sigma(P) Regulon in Bacillus thuringiensis
mSphere, Vol.7(1), e00967-21
02/23/2022
DOI: 10.1128/msphere.00967-21
PMCID: PMC8791391
PMID: 35080471
Abstract
Antimicrobial resistance is major concern for public health. beta-Lactams remain an important treatment option for many diseases. However, the spread of beta-lactam resistance continues to rise.
Bacillus thuringiensis and other members of the Bacillus cereus family are resistant to many beta-lactams. Resistance is dependent upon the extracytoplasmic function sigma factor sigma(P). We used label-free quantitative proteomics to identify proteins whose expression was dependent upon sigma(P). We compared the protein profiles of strains which either lacked sigma(P) or overexpressed sigma(P). We identified 8 members of the sigma(P) regulon which included four beta-lactamases as well as three penicillin-binding proteins (PBPs). Using transcriptional reporters, we confirmed that these genes are induced by beta-lactams in a sigma(P)-dependent manner. These genes were deleted individually or in various combinations to determine their role in resistance to a subset of beta-lactams, including ampicillin, methicillin, cephalexin, and cephalothin. We found that different combinations of beta-lactamases and PBPs are involved in resistance to different beta-lactams. Our data show that B. thuringiensis utilizes a suite of enzymes to protect itself from beta-lactam antibiotics. IMPORTANCE Antimicrobial resistance is major concern for public health. beta-Lactams remain an important treatment option for many diseases. However, the spread of beta-lactam resistance continues to rise. Many pathogens acquire antibiotic resistance from environmental bacteria. Thus, understanding beta-lactam resistance in environmental strains may provide insights into additional mechanisms of antibiotic resistance. Here, we describe how a single regulatory system, sigma(P), in B. thuringiensis controls expression of multiple genes involved in resistance to beta-lactams. Our findings indicate that some of these genes are partially redundant. Our data also suggest that the large number of genes controlled by sigma(P) results in increased resistance to a wider range of beta-lactam classes than any single gene could provide.
Details
- Title: Subtitle
- Identification of the Extracytoplasmic Function sigma Factor sigma(P) Regulon in Bacillus thuringiensis
- Creators
- Theresa D. Ho - Roy J. and Lucille A. Carver College of MedicineKelsie M. Nauta - Roy J. and Lucille A. Carver College of MedicineEmma K. Luhmann - Roy J. and Lucille A. Carver College of MedicineLilliana Radoshevich - Roy J. and Lucille A. Carver College of MedicineCraig D. Ellermeier - University of Iowa
- Resource Type
- Journal article
- Publication Details
- mSphere, Vol.7(1), e00967-21
- DOI
- 10.1128/msphere.00967-21
- PMID
- 35080471
- PMCID
- PMC8791391
- NLM abbreviation
- mSphere
- ISSN
- 2379-5042
- eISSN
- 2379-5042
- Publisher
- Amer Soc Microbiology
- Number of pages
- 16
- Grant note
- R21AI146769 / National Institute of Allergy and Infectious Diseases, NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 02/23/2022
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology
- Record Identifier
- 9984297431202771
Metrics
7 Record Views