Molecular mimicry between bacteria and sperm immobilization factor binding receptors and its role in infertility

Abstract

SIF, a sperm immobilization factor isolated from a sperm immobilizing strain of Staphylococcus aureus, causes immobilization, death, morphological alteration, decrease in Mg2+-dependent ATPase levels and loss of acrosome of mouse spermatozoa and infertility in vivo. SIF labelled with Fluorescein isothiocyanate (FITC) bound not only to mouse spermatozoa but also to various motile as well as non-motile bacteria, providing an evidence about existence of common SIF-binding receptors on spermatozoa and bacteria and hence, propagating the idea of molecular mimicry. Further, the corresponding SIF- binding receptors from mouse spermatozoa (MS-SBR) and representative bacteria {motile Gram-negative bacteria, Escherichia coli (E-SBR) and a non-motile Gram-positive bacteria Streptococcus pyogenes (S-SBR)} were isolated, purified and their ameliorative effect on SIF-induced sperm impairment and infertility was studied. Interestingly, not only MS-SBR, but the bacterial receptors also ameliorated the SIF-mediated compromised sperm parameters in vitro and infertility in vivo. Besides sperm impairment, SIF caused bacterial immobilization and alteration in morphology. The results showed that not only bacterial receptors, but MS-SBR also, showed the blocking activity. Further, assessment of specificity of SIF-receptor binding by calorimetric studies revealed that MS-SBR bound more strongly to SIF as compared to E- SBR/S-SBR (E-SBRgtS-SBR). Lastly, anti-MS-SBR newlinepolyclonal antibodies were generated to better understand the possible role of molecular mimicry in infertility. These anti-MS-SBR antibodies behaved as SIF which was demonstrated by labelling studies carried out with FITC- tagged anti-MS-SBR antibodies, wherein specific binding of anti-MS-SBR antibodies with spermatozoa and bacteria eventually authenticated the existence of shared antigenic determinants between spermatozoa and bacteria against common SIF.