The sensitivity of Bacillus subtilis to diverse antimicrobial compounds is influenced by Abh.
Abh is a transition state regulator of Bacillus subtilis that controls biofilm formation and the production of several diverse antimicrobial compounds. Using a high-throughput non-biased technique, we show for the first time that Abh influences the sensitivity of B. subtilis to diverse antimicrobial compounds. Following up on these findings with a combination of classical genetics and antibiotic susceptibility assays, we demonstrate that Abh influences cellular processes such as the remodelling of the cell wall. We present data demonstrating that the extracytoplasmic function sigma factor σ(X) controls resistance to β-lactam antibiotics by activating abh transcription. Downstream from Abh, activation of slrR expression by Abh is responsible for controlling the sensitivity of B. subtilis to such antibiotics due to the role that SlrR plays in regulating autolysin biosynthesis. The abh mutant additionally exhibits increased resistance to aminoglycoside antimicrobials. We confirm that aminoglycoside killing of B. subtilis is likely to be caused by oxidative damage but rule out the possibility that the increased resistance of the abh mutant to aminoglycosides is due to a general increase in resistance to oxidative stress.
Murray
Ewan J
EJ
Division of Molecular Microbiology, College of Life Sciences, MSI/WTB/JBC Complex, University of Dundee, Dundee DD1 5EH, UK.
Stanley-Wall
Nicola R
NR
D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005809:Genes, Regulator; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000096:biosynthesis; D018384:Oxidative Stress; D012808:Sigma Factor / Q000378:metabolism*; D018440:beta-Lactam Resistance; D047090:beta-Lactams / Q000494:pharmacology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C093265:SigX protein, Bacillus subtilis; D012808:Sigma Factor; D047090:beta-Lactams; D009238:N-Acetylmuramoyl-L-alanine Amidase