Search for MicroRNAs Expressed by Intracellular Bacterial Pathogens in Infected Mammalian Cells

Abstract

MicroRNAs are expressed by all multicellular organisms and play a critical role as post-transcriptional regulators of gene expression. Moreover, different microRNA species are known to influence the progression of a range of different diseases, including cancer and microbial infections. A number of different human viruses also encode microRNAs that can attenuate cellular innate immune responses and promote viral replication, and a fungal pathogen that infects plants has recently been shown to express microRNAs in infected cells that repress host cell immune responses and promote fungal pathogenesis. Here, we have used deep sequencing of total expressed small RNAs, as well as small RNAs associated with the cellular RNA-induced silencing complex RISC, to search for microRNAs that are potentially expressed by intracellular bacterial pathogens and translocated into infected animal cells. In the case of Legionella and Chlamydia and the two mycobacterial species M. smegmatis and M. tuberculosis, we failed to detect any bacterial small RNAs that had the characteristics expected for authentic microRNAs, although large numbers of small RNAs of bacterial origin could be recovered. However, a third mycobacterial species, M. marinum, did express an ∼23-nt small RNA that was bound by RISC and derived from an RNA stem-loop with the characteristics expected for a pre-microRNA. While intracellular expression of this candidate bacterial microRNA was too low to effectively repress target mRNA species in infected cultured cells in vitro, artificial overexpression of this potential bacterial pre-microRNA did result in the efficient repression of a target mRNA. This bacterial small RNA therefore represents the first candidate microRNA of bacterial origin.

Murine MicroRNA‐214 regulates intracellular adhesion molecule (ICAM1) gene expression in genital Chlamydia muridarum infection

“…Overall, this study provides an association between a specific miR (miR‐214), and its target gene ( ICAM1 ) in early stage C. muridarum infection. This study not only provides evidence of miR‐214‐dependent regulation of ICAM1 , which probably contributes to infiltration of neutrophils and pathology, but also augments the body of evidence supporting the regulatory role of miRs in Chlamydia pathogenesis . Possible ICAM1 regulation by miR‐214 was first suggested in C. muridarum ‐infected genital tract tissues (Fig.…”

Guinea pig genital tract lipidome reveals in vivo and in vitro regulation of phosphatidylcholine 16:0/18:1 and contribution to Chlamydia trachomatis serovar D infectivity

“…Transcriptome-wide or sequencing approaches have revealed the role for specific immune genes and associated pathways following infection with Ct-plasmid-sufficient and -deficient strains (Porcella et al 2015; Carlson et al 2008; Ferreira et al 2013; Qu et al 2015). Similarly, regulatory genetic species, namely microRNAs of bacterial and host origin have revealed the role(s) in growth and cellular function following infection (Derrick et al 2013; Furuse et al 2014; Gupta et al 2015; Yeruva et al 2014; Igietseme et al 2013). Proteomic studies have identified immunodominant, T- and B cell chlamydial antigens involved in primary infection and vaccination (Cruz-Fisher et al 2011; Wang et al 2010; Karunakaran et al 2015; Picard et al 2012).…”

Wolbachia small noncoding RNAs and their role in cross-kingdom communications

“…However, recent studies suggest that bacteria could also produce functional miRNA or miRNA-like snRNAs (12,13). In this study, we found that Wolbachia, as endosymbiotic bacteria, are able to encode snRNAs that act as effectors to modulate the expression of Wolbachia and mosquito host genes.…”