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 b...

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Main Authors: Lane B Buchanan, Zhongtian Shao, Ronald M Galiwango, Shirley Constable, David Zuanazzi, Victoria Menya Biribawa, Henry Rogers Ssemunywa, Annemarie Namuniina, Brenda Okech, Gabriella Edfeldt, Annelie Tjernlund, Aaron A R Tobian, Daniel E Park, Tony Pham, Maliha Aziz, Juan E Salazar, Sydney Nelson, Cindy M Liu, Rupert Kaul, Jessica L Prodger
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-04-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1013094
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author Lane B Buchanan
Zhongtian Shao
Ronald M Galiwango
Shirley Constable
David Zuanazzi
Victoria Menya Biribawa
Henry Rogers Ssemunywa
Annemarie Namuniina
Brenda Okech
Gabriella Edfeldt
Annelie Tjernlund
Aaron A R Tobian
Daniel E Park
Tony Pham
Maliha Aziz
Juan E Salazar
Sydney Nelson
Cindy M Liu
Rupert Kaul
Jessica L Prodger
author_facet Lane B Buchanan
Zhongtian Shao
Ronald M Galiwango
Shirley Constable
David Zuanazzi
Victoria Menya Biribawa
Henry Rogers Ssemunywa
Annemarie Namuniina
Brenda Okech
Gabriella Edfeldt
Annelie Tjernlund
Aaron A R Tobian
Daniel E Park
Tony Pham
Maliha Aziz
Juan E Salazar
Sydney Nelson
Cindy M Liu
Rupert Kaul
Jessica L Prodger
author_sort Lane B Buchanan
collection DOAJ
description 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.
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spelling doaj-art-2ee6772dad904e2f9f0ef62839163cef2025-08-20T02:13:55ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-04-01214e101309410.1371/journal.ppat.1013094HIV-associated penile anaerobes disrupt epithelial barrier integrity.Lane B BuchananZhongtian ShaoRonald M GaliwangoShirley ConstableDavid ZuanazziVictoria Menya BiribawaHenry Rogers SsemunywaAnnemarie NamuniinaBrenda OkechGabriella EdfeldtAnnelie TjernlundAaron A R TobianDaniel E ParkTony PhamMaliha AzizJuan E SalazarSydney NelsonCindy M LiuRupert KaulJessica L ProdgerSpecific 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.https://doi.org/10.1371/journal.ppat.1013094
spellingShingle Lane B Buchanan
Zhongtian Shao
Ronald M Galiwango
Shirley Constable
David Zuanazzi
Victoria Menya Biribawa
Henry Rogers Ssemunywa
Annemarie Namuniina
Brenda Okech
Gabriella Edfeldt
Annelie Tjernlund
Aaron A R Tobian
Daniel E Park
Tony Pham
Maliha Aziz
Juan E Salazar
Sydney Nelson
Cindy M Liu
Rupert Kaul
Jessica L Prodger
HIV-associated penile anaerobes disrupt epithelial barrier integrity.
PLoS Pathogens
title HIV-associated penile anaerobes disrupt epithelial barrier integrity.
title_full HIV-associated penile anaerobes disrupt epithelial barrier integrity.
title_fullStr HIV-associated penile anaerobes disrupt epithelial barrier integrity.
title_full_unstemmed HIV-associated penile anaerobes disrupt epithelial barrier integrity.
title_short HIV-associated penile anaerobes disrupt epithelial barrier integrity.
title_sort hiv associated penile anaerobes disrupt epithelial barrier integrity
url https://doi.org/10.1371/journal.ppat.1013094
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