IpaH

ipaH refers to a family of virulence genes encoding invasion plasmid antigen H proteins in Shigella species and enteroinvasive Escherichia coli (EIEC). The ipaH genes are carried primarily on the virulence plasmid pINV, though related homologs can be found in multiple copies on plasmids and, in some lineages, on the chromosome. This gene family is a hallmark of invasive enteric pathogens and is used as a molecular marker for these organisms in some diagnostic contexts.

Proteins encoded by ipaH are secreted effectors delivered to host cells by the type III secretion system. IpaH proteins belong to a family characterized by an N-terminal leucine-rich repeat (LRR) region that mediates substrate recognition and a C-terminal NEL (E3 ubiquitin ligase) domain that catalyzes ubiquitination of host proteins. Through ubiquitin-dependent manipulation of host signaling pathways, including components of the NF-κB pathway, IpaH effectors can dampen inflammatory responses and promote intracellular survival and evasion of host defenses.

Genetically, the ipaH family comprises numerous paralogs with substantial sequence diversity among Shigella and EIEC strains. The multicopy and diversified nature of ipaH genes contribute to functional redundancy and strain-specific effects, complicating attribution of specific functions to individual paralogs.

Because ipaH genes are highly conserved among Shigella and EIEC, they have become common molecular targets for diagnostic assays such as PCR. Detection accuracy depends on plasmid retention and may be influenced by cross-reactivity with other enteroinvasive bacteria.

Overall, ipaH is a key virulence determinant in Shigella and EIEC, reflecting the role of host ubiquitination manipulation in bacterial pathogenesis and serving as a useful molecular marker in clinical microbiology.