Buchanan Lane B, Shao Zhongtian, Galiwango Ronald M, Constable Shirley, Zuanazzi David, Biribawa Victoria Menya, Ssemunywa Henry Rogers, Namuniina Annemarie, Okech Brenda, Edfeldt Gabriella, Tjernlund Annelie, Tobian Aaron A R, Park Daniel E, Pham Tony, Aziz Maliha, Salazar Juan E, Nelson Sydney, Liu Cindy M, Kaul Rupert, Prodger Jessica L
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Rakai Health Sciences Program, Rakai, Uganda.
PLoS Pathog. 2025 Apr 17;21(4):e1013094. doi: 10.1371/journal.ppat.1013094. eCollection 2025 Apr.
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.
阴茎微生物群中的特定厌氧类群——与血清转化、炎症和免疫细胞相关的细菌（BASIC）物种——会增强HIV-1易感性，部分原因是将易感细胞募集到包皮内层。然而，它们对上皮屏障完整性的影响尚未见报道。我们使用了116名接受自愿男性包皮环切术男性的包皮组织和阴茎拭子，评估了BASIC物种与包皮上皮厚度、连接蛋白表达和细胞增殖之间的关系。BASIC物种的绝对丰度与上皮连接蛋白claudin-1和E-钙黏蛋白的组织表达降低以及阴茎分泌物中可溶性E-钙黏蛋白升高有关，提示存在蛋白水解切割。在对照类群丰度高但BASIC物种水平不高的参与者中未观察到这些效应。研究表明，BASIC物种双栖普雷沃菌，而非厌氧消化链球菌或微小戴尔斯特菌，可在体外直接降解重组人E-钙黏蛋白并增加包皮上皮细胞中可溶性E-钙黏蛋白的释放。在体内，BASIC物种的绝对丰度还与有核上皮增厚和角质形成细胞增殖增加有关，角质层厚度无变化。因此，除了先前描述的靶细胞募集外，BASIC物种可能通过直接破坏上皮完整性来增强阴茎对HIV的易感性。
