Inflammatory bowel disease is a complex condition with a multifactorial etiology. An interplay of various factors can lead to an inflamed gut with the overproduction of host-defense peptides (HDPs) and microbiome alterations, such as increases in pathogenic bacteria. Through processes involving either core gene regulation or acquisition of new genes, bacteria have evolved mechanisms to resist HDPs. Previously, a novel genetic locus, arlABC, was identified in adherent-invasive Escherichia coli (AIEC) strain NRG857c that contributes to high-level HDP resistance. ArlC is an outer membrane protease, but the function(s) of ArlA and ArlB are unknown. Thus, characterization was performed on strains mutated in these genes. Lipopolysaccharide gels suggest a change in the core structure of the mutant strains, but several phenotypic assays gave varying results. We demonstrate that the ArlB protein is regulated by the PhoPQ two-component system. We anticipate that these investigations will lead to a better understanding of HDP resistance in AIEC.