Infertility affects 8%–12% of couples worldwide [1] of these, 50% are infertile due to male factor infertility [2]. Multiple factors including endocrine disorders, lifestyle, varicocele, ejaculatory disorders, hypogonadism, genetic defects, environmental, idiopathic and urogenital tract infections are classic causes of male infertility [3,4]. Acute and chronic infections of the male reproductive system may disrupt spermatozoa function and the entire spermatogenic process, causing qualitative and quantitative sperm alterations [4,5]. The presence of bacteria in the semen can originate from the male urogenital tract [6] or be introduced during semen collection [7]. Pathogens including Staphylococcus, Streptococcus, Mycoplasma, Pseudomonas, Corynebacterium or Bacillus have been described in the ejaculates of healthy bulls [8]. Bacterial infection has many negative effects on various parameters in sperm cells, including reduced sperm concentration, viability and impaired morphology [9,10], a decrease in sperm motility [11] acrosomal damage [12] and an increase in sAR in human sperm [13]. Bacteria like Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) deteriorate sperm motility, morphology and sperm count [[14], [15], [16]]. Under in vitro conditions, bacteria can cause an increase in sperm production of reactive oxygen species leading to lipid peroxidation and damage to sperm membranes [17]. These events are associated with a decline in male fertility [18].

Sperm cells undergo a number of physical and biochemical changes in the female reproductive tract, collectively called capacitation. Only capacitated sperm can undergo the physiological acrosomal exocytosis (acrosome reaction (AR)) process near or on the oocyte, which allows the spermatozoon to penetrate and fertilize the egg. Several intracellular changes are known to occur during sperm capacitation, including increase of: cholesterol efflux, membrane fluidity, intracellular Ca2+, cAMP concentrations, protein kinase A (PKA) activity, protein tyrosine phosphorylation (PTP), actin polymerization, and changes in hyperactivated and chemostatic motility [19]. Inhibition of PKA, PTP or actin polymerization prevent the occurrence of proper capacitation resulting in sAR.

Spontaneous AR (sAR) can occur under some conditions, and sperm samples containing a high proportion of cells that underwent sAR result in poor success in human IVF [20]. Sperm are endowed with several mechanisms that protect them from sAR, including calmodulin-kinase II (CaMKII) and phospholipase D (PLD), two distinct pathways that enhance F-actin formation during sperm capacitation [21]. Moreover, inhibition of PKA a key enzyme that mediates sperm capacitation and actin polymerization [22], results in an increase in sAR [23]. In our recent study we show that hyperacetylation of proteins during sperm capacitation reduces sAR dependent on CaMKII but independent of PKA activity [24]. We also show that inhibition of one metabolic pathway, glycolysis or mitochondrial respiration did not affect sAR level whereas significant increase is observed when the two pathways are inhibited [25].

In this study, we show that the interaction between E. coli, or P. aeruginosa and sperm induces sAR due to the reduction of PKA and protein tyrosine phosphorylation activities, providing a possible link between infection and infertility.