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. 2022 Jun 26;11(7):855. doi: 10.3390/antibiotics11070855

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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The upregulation of the Bla enzymes occurs when the two-component signaling system comes into contact with β-lactam antibiotics. A molecule of β-lactam antibiotic binds to active-site serine of the BlaR1 enzyme on the outside of outer membrane (Step 1). A conformational change occurs that releases the BlaR2 on the inside of the cellular envelop (Step 2). BlaR2 cleaves Blar1 of the DNA to allow for the transcription of downstream resistance genes (Step 3). The β-Lactamase BlaZ is produced from downstream genes (Step 4). BlaZ is transported out the cell, and the signal sequence is cleaved off the protein (Step 5). The BlaZ β-lactamase starts hydrolyzing incoming antibiotics (Step 6).