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When these mutants were compared to the pgsA745 cell line, a CHO xylosyltransferase mutant generated previously using chemical mutagenesis, an unexpected result was obtained. Bacterial invasion of pgsA745 cells by group B Streptococcus (GBS), group A\n            <jats:italic>Streptococcus<\/jats:italic>\n            , and\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            was markedly reduced compared to the invasion of wild-type cells, but newly generated CRISPR-\n            <jats:italic>cas9<\/jats:italic>\n            mutants were only resistant to GBS. Invasion of pgsA745 cells was not restored by transfection with xylosyltransferase, suggesting that an additional mutation conferring panresistance to multiple bacteria was present in pgsA745 cells. Whole-genome sequencing and transcriptome sequencing (RNA-Seq) uncovered a deletion in the gene encoding the laminin subunit \u03b12 (\n            <jats:italic>Lama2<\/jats:italic>\n            ) that eliminated much of domain L4a. Silencing of the long\n            <jats:italic>Lama2<\/jats:italic>\n            isoform in wild-type cells strongly reduced bacterial invasion, whereas transfection with human\n            <jats:italic>LAMA2<\/jats:italic>\n            cDNA significantly enhanced invasion in pgsA745 cells. The addition of exogenous laminin-\u03b12\u03b21\u03b31\/laminin-\u03b12\u03b22\u03b31 strongly increased bacterial invasion in CHO cells, as well as in human alveolar basal epithelial and human brain microvascular endothelial cells. Thus, the L4a domain in laminin \u03b12 is important for cellular invasion by a number of bacterial pathogens.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Pathogenic bacteria penetrate host cellular barriers by attachment to extracellular matrix molecules, such as proteoglycans, laminins, and collagens, leading to invasion of epithelial and endothelial cells. Here, we show that cellular invasion by the human pathogens group B\n            <jats:italic>Streptococcus<\/jats:italic>\n            , group A\n            <jats:italic>Streptococcus<\/jats:italic>\n            , and\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            depends on a specific domain of the laminin \u03b12 subunit. This finding may provide new leads for the molecular pathogenesis of these bacteria and the development of novel antimicrobial drugs.\n          <\/jats:p>","DOI":"10.1128\/mbio.02128-16","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T01:25:30Z","timestamp":1484097930000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Whole-Genome Sequencing of Invasion-Resistant Cells Identifies Laminin \u03b12 as a Host Factor for Bacterial Invasion"],"prefix":"10.1128","volume":"8","author":[{"given":"Xander M.","family":"van Wijk","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"D\u00f6hrmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn M.","family":"Hallstr\u00f6m","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, H\u00f8rsholm, Denmark"},{"name":"Royal Institute of Technology, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangzhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California, San Diego, La Jolla, California, USA"},{"name":"Department of Bioengineering, University of California, San Diego, La Jolla, California, USA"},{"name":"Novo Nordisk Foundation Center for Biosustainability, University of California, San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn G.","family":"Voldborg","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center 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