eCommons

 

Bacillus Subtilis Extracytoplasmic Function Sigma Factors Control Antibiotic Production And Resistance

Other Titles

Author(s)

Abstract

Bacillus subtilis, the model organism for Gram-positive bacteria, expresses seven extracytoplasmic function (ECF) [sigma] factors (called [sigma]M, [sigma]W, [sigma]X, [sigma]Y, [sigma]V, [sigma]Z and [sigma]YlaC). [sigma]M, [sigma]W, [sigma]X, and [sigma]V are well-characterized and mediate cell envelope stress responses. The functions of [sigma]Y, [sigma]Z and [sigma]YlaC remain largely unknown. One challenge in understanding the regulatory roles of ECF [sigma] factor is that they display significant redundancy in their regulons. In this study, we investigate the regulation of B. subtilis antibiotic production and resistance by ECF [sigma] factors using both global analytical techniques (cDNA microarrays, phenotypic arrays, and transposon mutagenesis) and classical genetic and physiological tests. This work began with the observation that a triple sigMWX mutant (strain [DELTA]MWX) lost its ability to inhibit the growth of other bacilli strains. We present evidence that deletions of [sigma]X and [sigma]M underlie this phenotype and that in wild type cells these ECF [sigma] factors activate the expression of a transcription factor Abh. Abh stimulates the production of a peptide antibiotic called sublancin, which is able to inhibit the growth of other bacilli. We also compared the transcriptomic profiles and phenotypic traits of strains lacking these three [sigma] factors ([DELTA]MWX) and all 7 ECF [sigma] factors ([DELTA]7ECF) with a wild type strain. Deletion of all 7 ECF [sigma] factors affects the i transcriptions of over 80 genes, most of which are regulated by [sigma]M, [sigma]W, or [sigma]X. The [DELTA]MWX and [DELTA]7ECF strains are more sensitive to several cell envelope disrupting compounds when compared to wild type including two [beta]-lactam antibiotics (aztreonam and cefuroxime). Finally, we investigated the ECF [sigma] factor-dependent genetic and biochemical mechanisms that mediate resistance to cefuroxime. [sigma]M is the major determinant in cefuroxime resistance with [sigma]X playing a smaller role. These [sigma] factors regulate at least three pathways involving the regulatory proteins Abh and Spx, and a cyclic-di-AMP synthase DisA. Collectively, the data in this work suggests that ECF [sigma] factors regulate an intricate regulatory network that contributes to both antibiotic production and resistance in B. subtilis. ii

Journal / Series

Volume & Issue

Description

Sponsorship

Date Issued

2012-05-27

Publisher

Keywords

bacillus subtilis; extracytoplasmic function sigma factors; antibiotic

Location

Effective Date

Expiration Date

Sector

Employer

Union

Union Local

NAICS

Number of Workers

Committee Chair

Helmann, John D

Committee Co-Chair

Committee Member

Angert, Esther R.
Shapleigh, James P
Nicholson, Linda K
Peters, Joseph E.

Degree Discipline

Microbiology

Degree Name

Ph. D., Microbiology

Degree Level

Doctor of Philosophy

Related Version

Related DOI

Related To

Related Part

Based on Related Item

Has Other Format(s)

Part of Related Item

Related To

Related Publication(s)

Link(s) to Related Publication(s)

References

Link(s) to Reference(s)

Previously Published As

Government Document

ISBN

ISMN

ISSN

Other Identifiers

Rights

Rights URI

Types

dissertation or thesis

Accessibility Feature

Accessibility Hazard

Accessibility Summary

Link(s) to Catalog Record