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Antibiotics are cytotoxic secondary metabolites that are isolated from Nature. The antibacterial antibiotics disproportionately target bacterial protein structure that is distinct from eukaryotic protein structure, notably within the ribosome and within the pathways for bacterial cell\u2010wall biosynthesis (for which there is not a eukaryotic counterpart). This review focuses on a pre\u2010eminent class of antibiotics\u2014the \u03b2\u2010lactams, exemplified by the penicillins and cephalosporins\u2014from the perspective of the evolving mechanisms for bacterial resistance. The mechanism of action of the \u03b2\u2010lactams is bacterial cell\u2010wall destruction. In the monoderm (single membrane, Gram\u2010positive staining) pathogen <jats:italic>Staphylococcus aureus<\/jats:italic> the dominant resistance mechanism is expression of a \u03b2\u2010lactam\u2010unreactive transpeptidase enzyme that functions in cell\u2010wall construction. In the diderm (dual membrane, Gram\u2010negative staining) pathogen <jats:italic>Pseudomonas aeruginosa<\/jats:italic> a dominant resistance mechanism (among several) is expression of a hydrolytic enzyme that destroys the critical \u03b2\u2010lactam ring of the antibiotic. The key sensing mechanism used by <jats:italic>P. aeruginosa<\/jats:italic> is monitoring the molecular difference between cell\u2010wall construction and cell\u2010wall deconstruction. In both bacteria, the resistance pathways are manifested only when the bacteria detect the presence of \u03b2\u2010lactams. This review summarizes how the \u03b2\u2010lactams are sensed and how the resistance mechanisms are manifested, with the expectation that preventing these processes will be critical to future chemotherapeutic control of multidrug resistant bacteria.<\/jats:p>","DOI":"10.1002\/pro.3737","type":"journal-article","created":{"date-parts":[[2019,10,6]],"date-time":"2019-10-06T08:14:41Z","timestamp":1570349681000},"page":"629-646","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Constructing and deconstructing the bacterial cell wall"],"prefix":"10.1002","volume":"29","author":[{"given":"Jed F.","family":"Fisher","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Notre Dame  South Bend 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