Escherichia coli clonal complex 95 represents a cosmopolitan, genetically diverse lineage, and the extensive substructure observed in this lineage is epidemiologically and clinically relevant. The frequency with which CC95 strains are responsible for extraintestinal infection appears to have been stable over the past 15 years. However, the different subgroups identified within this lineage have an epidemic structure depending on the host, sample, continent, and time. Thus, the evolution and spread of strains belonging to CC95 are very different from those of another cosmopolitan human-associated clonal complex, CC131, which has increased significantly in frequency as a cause of extraintestinal infection over the past 15 years due to the evolution and spread of two very closely related, nearly monomorphic lineages.

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.

Spermatogenesis and sperm maturation are complex processes mediated by a variety of proteins present in the testicular and epididymal mileu. In the recent years, functional characterization of these proteins is being studied by genetic manipulations that involve targeted over expression or knock down of specific genes. In this study, we adopted FuGENE 6-based in vivo transfection of rat cauda epididymis with pGFP-V-RS plasmid that encodes shRNA to knock down Pate mRNA levels to implicate a possible role for this gene in sperm function. The mRNA levels of Pate gene were significantly decreased in HEK cells as well as in cauda of rats upon transfection with pGFP-V-RS plasmid that encodes shRNA targeting Pate gene. Spermatozoa obtained from the transfected cauda displayed impairment in capacitation and acrosome reaction. Furthermore, rats subjected to in vivo transfection to knock down Pate mRNA levels had compromised fertility. Results of our study indicate a role for Pate gene in sperm function and can be exploited as a potential male contraceptive target.

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