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Here, to identify the receptor for three other narrow-spectrum subclass IId bacteriocins - garvicins A, B and C (GarA-C) <jats:italic>Lactococcus garvieae<\/jats:italic> mutants resistant to bacteriocins were generated and sequenced to look for mutations responsible for resistance. Spontaneous mutants had their whole genome sequenced while in mutants obtained by integration of pGhost9::IS<jats:italic>S1<\/jats:italic> regions flanking the integration site were sequenced. For both types of mutants mutations were found in genes encoding Man-PTS components IIC and IID indicating that Man-PTS likely serves as the receptor for these bacteriocins as well. This was subsequently confirmed by deletion of the <jats:italic>man-PTS<\/jats:italic> operon in the bacteriocin-sensitive <jats:italic>L<\/jats:italic>. <jats:italic>garvieae<\/jats:italic> IBB3403, which resulted in resistant cells, and by heterologous expression of appropriate <jats:italic>man-PTS<\/jats:italic> genes in the resistant <jats:italic>Lactococcus lactis<\/jats:italic> strains, which resulted in sensitive cells. GarA, GarB, GarC and other Man-PTS-targeting bacteriocins differ in the amino acid sequence and activity spectrum, suggesting that they interact with the receptor through distinct binding patterns. Comparative analyses and genetic studies identified a previously unrecognized extracellular loop of Man-PTS subunit IID (\u03b3+) implicated in the <jats:italic>L<\/jats:italic>. <jats:italic>garvieae<\/jats:italic> sensitivity to the bacteriocins studied here. Additionally, individual amino acids localized mostly in the sugar channel-forming transmembrane parts of subunit IIC or in the extracellular parts of IID likely involved in the interaction with each bacteriocin were specified. Finally, template-based 3D models of Man-PTS subunits IIC and IID were built to allow a deeper insight into the Man-PTS structure and functioning.<\/jats:p>","DOI":"10.1038\/s41598-018-34087-2","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T11:26:41Z","timestamp":1539948401000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The extracellular loop of Man-PTS subunit IID is responsible for the sensitivity of Lactococcus garvieae to garvicins A, B and C"],"prefix":"10.1038","volume":"8","author":[{"given":"Aleksandra","family":"Tymoszewska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dzung B.","family":"Diep","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4725-760X","authenticated-orcid":false,"given":"Tamara","family":"Aleksandrzak-Piekarczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,10,25]]},"reference":[{"key":"34087_CR1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1128\/mr.57.3.543-594.1993","volume":"57","author":"PW Postma","year":"1993","unstructured":"Postma, P. 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