The dissection of Β-lactam resistance in Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis

β-lactam antibiotics, such as penicillin, have been important for treating bacterial infections. However, the prevalence of antibiotic resistant has increased over time. Understanding how bacteria adapt to and overcome antibiotics is imperative for the future treatment of antibiotic resistant infections. In Bacillus cereus, anthracis, and thuringiensis, β-lactam resistance in conferred by β-lactamases and penicillin binding proteins. These proteins either directly degrade β-lactam antibiotics or modify the target of the β-lactam so they can no longer bind and kill the bacteria. These proteins are not produced unless they are needed. To produce these proteins bacteria have developed mechanisms to sense the presence of β-lactams and activate transcription of β-lactamases and PBPs.

In Bacillus cereus, anthracis, and thuringiensis the transcription of β-lactamases and PBPs is controlled by a protein called σ^P. σ^P belongs to a group of transcription factors call extracytoplasmic function (ECF) σ factors. ECF σ factors are inhibited in the absence of stress and are released in the presence of stress. σ^P is inhibited by the anti-σ factor RsiP in the absence of β-lactam antibiotics. Here we show when the bacteria sense the presence of β-lactams, RsiP is sequentially degraded by two proteases: SipP and RasP. This results in the release of σ^P and transcription of β-lactamases and PBPs which neutralize the threat of β-lactams. Future work aims to exploit these findings to develop novel antibiotics that prevent the transcription of antibiotic resistance genes.