Uropathogenic Escherichia coli (UPEC) induced antimicrobial gene expression in the male reproductive tract of rat: evaluation of the potential of Defensin 21 to limit infection

Abstract

SUMMARYEscherichia coli (E. coli) is a common pathogen in epididymitis, which represents a prevalent entity in male reproductive tract infections (RTI). Although current treatment regimens using antibiotics are satisfactory, development of antimicrobial resistance by the pathogen represents a challenge in the management of RTI. Hence, identification of antimicrobial peptides as alternatives to antibiotics has gained importance. We demonstrate that in a rat epididymo-orchitis model induced with uropathogenic E. coli (UPEC) strain MTCC 729, the expression of defensins and defensin-like Spag11 genes are induced in the epididymis and testes. The induction of antimicrobial gene expression is paralleled by phosphorylation of the NF-kB subunit p65 and the inhibitor of NFkB (IkB-alpha), decreased levels of histone deacetylase 1 and increased methylation of Histone 3, indicating the role of classical Toll-like receptor mediated signaling and epigenetic regulation. Recombinant Defensin 21, when administered to UPEC-infected rats, substantially reduced the bacterial load in the epididymis and testis and proved to be more effective than gentamycin. The ability of Defensin 21 to limit RTI provides support that antibacterial proteins of the male reproductive tract may be used as potential alternatives to antibiotics in treatment of this disease.

Tlr1‐13, Nod1/2 and antimicrobial gene expression in the epididymis and testis of rats with alloxan‐induced diabetes

“…Production of antimicrobial peptides is an integral part of innate immunity and is crucial to prevent infections. We previously reported that Defb and Spag11 genes expressed in epididymis and testis are implicated in the endotoxin or bacterial‐induced host responses and that administration of DEFB21 can reduce uropathogenic E. coli load in a rat model of epididymitis (Biswas, Bhushan, Meinhardt, & Yenugu, ; Biswas & Yenugu, , ). Alteration in the expression of innate immune machinery in different organ systems under diabetic conditions is well reported.…”

Epididymitis: revelations at the convergence of clinical and basic sciences

“… 62 86 87 In the testis, atrophy, swelling, edema, and enlargement of the gonad are observed. 77 83 85 In contrast to men, in the animals models testicular weight was unaltered in the initial stages of the disease, 77 86 while a slight decrease in testicular volume was documented at later time points. 88 These changes reflect an acute response to the infection that appears within 24–48 h after inoculation, 54 86 87 88 and are most prominent up to 7–14 days postinfection, then subside and vanish after 1 month.…”

“…An alternative tool to induce epididymitis is the administration of bacterial lipopolysaccharide (LPS), a major structural component of the outer membrane of Gram-negative bacteria, instead of live bacteria. 24 82 83 LPS is a well-characterized inducer of inflammation. It binds preferentially to TLR4 and induces a signaling cascade involving the accessory receptor proteins, MD2 and CD14, and several adapter proteins, such as myeloid differentiation factor 88 (MyD88).…”

“…In accordance with clinical observations in epididymitis patients, reddening, swelling, and enlargement of the epididymis is one of the prominent signs of bacterial epididymitis in experimental animals. 54 62 74 75 77 83 85 Indications for the infection in the scrotum range from mild edema to severe erythema. 62 86 87 In the testis, atrophy, swelling, edema, and enlargement of the gonad are observed.…”

“… 82 In turn, intravenous administration of Defb21 to E. coli -infected rats significantly decreased the number of bacterial colony-forming units. 83 Sperm-associated antigen 11 (SPAG 11) is a peptide of the defensin family that is involved in sperm maturation and host defense mechanisms in the epididymis. 82 Spag11b (also known as Bin1b ) expression decreases following bacterial infection in the murine epididymis.…”