Many pathogenic bacteria suppress epithelial exfoliation (rapid shedding of cells) to enhance host colonization. Common to these pathogens is their ability to bind carcinoembryonic antigen-related cell adhesion molecules (CEACAMs). Neisseria gonorrhoeae binding to CEACAM upregulates the expression of CD105, which is necessary to suppress exfoliation. Muenzner and Hauck find that CEACAM engagement by N. gonorrhoeae in mice leads to the release of nitric oxide (NO) by the bacteria, which initiates a protein kinase G-dependent signalling cascade in the host that upregulates CD105 expression, leading to suppression of exfoliation. Blockade of this pathway led to the re-establishment of exfoliation, which inhibited N. gonorrhoeae vaginal colonization in mice, suggesting that targeting this pathway could be a promising treatment strategy.