{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:53:25Z","timestamp":1787237605973,"version":"build-2736575974"},"reference-count":44,"publisher":"Microbiology Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:p>\n                    P128 is an anti-staphylococcal protein consisting of the\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    phage-K-derived tail-associated muralytic enzyme (TAME) catalytic domain (Lys16) fused with the cell-wall-binding SH3b domain of lysostaphin. In order to understand the mechanism of action and emergence of resistance to P128, we isolated mutants of\n                    <jats:italic>Staphylococcus<\/jats:italic>\n                    spp., including meticillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA), resistant to P128. In addition to P128, the mutants also showed resistance to Lys16, the catalytic domain of P128. The mutants showed loss of fitness as shown by reduced rate of growth\n                    <jats:italic>in vitro<\/jats:italic>\n                    . One of the mutants tested was found to show reduced virulence in animal models of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    septicaemia suggesting loss of fitness\n                    <jats:italic>in vivo<\/jats:italic>\n                    as well. Analysis of the antibiotic sensitivity pattern showed that the mutants derived from MRSA strains had become sensitive to meticillin and other \u03b2-lactams. Interestingly, the mutant cells were resistant to the lytic action of phage K, although the phage was able to adsorb to these cells. Sequencing of the\n                    <jats:italic>femA<\/jats:italic>\n                    gene of three P128-resistant mutants showed either a truncation or deletion in\n                    <jats:italic>femA<\/jats:italic>\n                    , suggesting that improper cross-bridge formation in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    could be causing resistance to P128. Using glutathione\n                    <jats:italic>S<\/jats:italic>\n                    -transferase (GST) fusion peptides as substrates it was found that both P128 and Lys16 were capable of cleaving a pentaglycine sequence, suggesting that P128 might be killing\n                    <jats:italic>S. aureus<\/jats:italic>\n                    by cleaving the pentaglycine cross-bridge of peptidoglycan. Moreover, peptides corresponding to the reported cross-bridge of\n                    <jats:italic>Staphylococcus haemolyticus<\/jats:italic>\n                    (GGSGG, AGSGG), which were not cleaved by lysostaphin, were cleaved efficiently by P128. This was also reflected in high sensitivity of\n                    <jats:italic>S. haemolyticus<\/jats:italic>\n                    to P128. This showed that in spite of sharing a common mechanism of action with lysostaphin, P128 has unique properties, which allow it to act on certain lysostaphin-resistant\n                    <jats:italic>Staphylococcus<\/jats:italic>\n                    strains.\n                  <\/jats:p>","DOI":"10.1099\/mic.0.079111-0","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T00:07:59Z","timestamp":1405382879000},"page":"2157-2169","source":"Crossref","is-referenced-by-count":27,"title":["Bacteriophage-derived CHAP domain protein, P128, kills Staphylococcus cells by cleaving interpeptide cross-bridge of peptidoglycan"],"prefix":"10.1099","volume":"160","author":[{"given":"Sudarson","family":"Sundarrajan","sequence":"first","affiliation":[{"name":"GangaGen Biotechnologies Pvt. 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