Targeted disruption of the gene in impairs membrane integrity and host symbiont dynamics.

The obligate symbiosis between pea aphids () and represents metabolic interdependence between the host insect and its bacterial symbiont. has a highly reduced genome that has lost nearly all phospholipid synthesis genes except , encoding a cardiolipin synthase homologue. We employed antisense, cell-penetrating peptide (CPP)-conjugated synthetic peptide nucleic acids (PNAs) to knock down in . This intervention resulted in significant downregulation of expression, lowered titers, pronounced morphological distortions, and reduced aphid reproduction. Notably, cells were often detected in the aphid gut following anti- PNAs treatment, deviating from their typical intracellular niche within bacteriocytes. Collectively, the gene is critical for maintaining integrity, proper cellular localization, and symbiont-host interactions. Given that the retention of is a common feature among many obligate endosymbionts despite massive gene loss, our findings offer key insights into the evolutionary principles shaping symbiotic relationships involving membrane biology.