{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T03:14:36Z","timestamp":1794021276066,"version":"4.8.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Newby Family"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The epididymal lumen is an immunologically distinct environment. It maintains tolerance for the naturally antigenic spermatozoa to allow their maturation into functional cells while simultaneously defending against pathogens that can ascend the male tract and cause infertility. We previously demonstrated that a nonpathological amyloid matrix that includes several cystatin-related epididymal spermatogenic (CRES) subgroup family members is distributed throughout the mouse epididymal lumen but its function was unknown. Here, we reveal a role for the epididymal amyloid matrix in host defense and demonstrate that the CRES amyloids and CD-1 mouse epididymal amyloid matrix exhibit potent antimicrobial activity against bacterial strains that commonly cause epididymal infections in men. We show the CRES and epididymal amyloids use several defense mechanisms including bacterial trapping, disruption of bacterial membranes and promotion of unique bacterial ghost-like structures. Remarkably, these antimicrobial actions varied depending on the bacterial strain indicating CRES amyloids and the epididymal amyloids elicit strain-specific host defense responses. We also demonstrate that the CRES monomer and immature assemblies of the epididymal amyloid transitioned into advanced structures in the presence of bacteria, suggesting their amyloid-forming\/shape-shifting properties allows for a rapid reaction to a pathogen and provides an inherent plasticity in their host defense response. Together, our studies reveal new mechanistic insight into how the male reproductive tract defends against pathogens. Future studies using a mouse model for human epididymitis are needed to establish the epididymal amyloid responses to pathogens in vivo. Broadly, our studies provide an example of why nature has maintained the amyloid fold throughout evolution.<\/jats:p>","DOI":"10.1093\/molehr\/gaac038","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T12:39:05Z","timestamp":1668170345000},"source":"Crossref","is-referenced-by-count":19,"title":["Host defense functions of the epididymal amyloid matrix"],"prefix":"10.1093","volume":"28","author":[{"given":"Caitlyn","family":"Myers","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center , Lubbock, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Catherine","family":"Hastert","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences Microscopy, Texas Tech University , Lubbock, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2903-1690","authenticated-orcid":false,"given":"Gail A","family":"Cornwall","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center , Lubbock, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"2022113011295249100_gaac038-B1","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1128\/AEM.02750-06","article-title":"Assessment and interpretation of bacterial viability by using the LIVE\/DEAD BacLight kit in combination with flow cytometry","volume":"73","author":"Berney","year":"2007","journal-title":"Appl Environ Microbiol"},{"key":"2022113011295249100_gaac038-B2","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/j.bbapap.2010.04.001","article-title":"Molecular mechanism of Thioflavin-T binding to amyloid fibrils","volume":"1804","author":"Biancalana","year":"2010","journal-title":"Biochim Biophys Acta"},{"key":"2022113011295249100_gaac038-B3","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/385787a0","article-title":"Instability, unfolding and aggregation of human lysozyme variants underlying amyloid fibrillogenesis","volume":"385","author":"Booth","year":"1997","journal-title":"Nature"},{"key":"2022113011295249100_gaac038-B4","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"2022113011295249100_gaac038-B5","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1126\/science.1218831","article-title":"Human alpha-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets","volume":"337","author":"Chu","year":"2012","journal-title":"Science"},{"key":"2022113011295249100_gaac038-B6","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1210\/en.2002-220997","article-title":"The cystatin-related epididymal spermatogenic protein inhibits the serine protease prohormone convertase 2","volume":"144","author":"Cornwall","year":"2003","journal-title":"Endocrinology"},{"key":"2022113011295249100_gaac038-B7","doi-asserted-by":"crossref","first-page":"28781","DOI":"10.1038\/srep28781","article-title":"J. 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