HIV-associated penile anaerobes disrupt epithelial barrier integrity

Specific anaerobic taxa within the penile microbiome-the Bacteria Associated with Seroconversion, Inflammation and Immune Cells (BASIC) species-enhance HIV-1 susceptibility, in part by recruiting susceptible cells to the inner foreskin. However, their effect on epithelial barrier integrity has not been described. Using foreskin tissues and penile swabs from 116 males undergoing voluntary medical male circumcision, we assessed the relationship between BASIC species and foreskin epithelial thickness, junction protein expression, and cellular proliferation. The absolute abundance of BASIC species was associated with reduced tissue expression of the epithelial junction proteins claudin-1 and E-cadherin, and with elevated soluble E-cadherin in penile secretions, suggesting proteolytic cleavage. These effects were not seen in participants with a high abundance of control taxa without high levels of BASIC species. The BASIC species Prevotella bivia, but not Peptostreptococcus anaerobius or Dialister micraerophilus, was shown to directly degrade recombinant human E-cadherin and to increase the release of soluble E-cadherin from foreskin epithelial cells in vitro. In vivo BASIC species absolute abundance was also linked to a thicker nucleated epithelium and increased keratinocyte proliferation, with no change in stratum corneum thickness. Therefore, BASIC species may enhance penile HIV susceptibility by directly disrupting epithelial integrity, in addition to previously described target cell recruitment.