Table 1.

Examples of virulence processes under RNA-based control.

Species	RNA/RNase/RNA-modifying enzyme	Mechanism	Virulence function	References
E. coli	AfaR	trans-encoded ncRNA destabilizes the afaD mRNA by binding to the 5′-UTR	Regulation of expression of afimbrial adhesins of the Afa family in ExPEC	64
	CsrABC	CsrA: RNA binding protein, CsrB/CsrC: trans-encoded CsrA-binding RNAs CsrA binds to the LEE4 mRNA, overexpression of CsrA represses expression of the LEE1-5 transcripts through a reduction of GrlA and Ler in EPEC CsrA binds to the 5′-UTR of the pga mRNA encoding biofilm matrix components CsrA directly binds and stabilizes the flhDC transcript	Global control of pathogenesis (colonization, immune resistance), stress responses and metabolism. Expression of type 1 fimbriae and Pef fimbriae. Control of c-di-GMP synthesis Important for pedestal formation and for membrane depolarization of epithelial cells, in EHEC, Control of biofilm formation and motility	26,27,31,52
	GadY	trans-encoded ncRNA interacts with 3′-UTR of the gadY transcript in the gadX-gadY mRNA which stimulates processing into stable gadX and gadY transcripts	Glutamate-dependent extreme acid resistance	136
	GcvB	trans-encoded ncRNA Hfq-dependent a 30 nt stretch of G/U residues of GcvB recognize extended C/A elements overlapping the ribosome binding site in some targets acts by direct antisense interaction with the csgD 5′-UTR	Repression of curli biogenesis. Regulation of ABC transporters and amino acid biosynthesis genes	44
	GlmY, GlmZ	trans-encoded ncRNAs destabilization of mRNA transcripts and facilitation of translation	Control of pathogenesis, regulation of the LEE4 and LEE5 operons, the LEE-encoded effector EspFu and the non-LEE-encoded effector NleA in EHEC, promote expression of the curli adhesin, repress tryptophan metabolism genes, and promote acid resistance	46-48,53
	McaS	trans-encoded ncRNA resembles CsrB and sequestrates CsrA, represses in collaboration with Hfq expression of the transcriptional activator gene csgD and activates the flhDC gene	Repression of curli biogenesis, Activation of flagella synthesis	44
	OmrA, OmrB	trans-encoded ncRNAs sibling ncRNA encoded in tandem, act by direct antisense interaction with the respective 5′-UTR, Hfq-dependent, highly redundant functions	Regulation of curli formation, motility and iron sequestration. Regulation of outer membrane proteins implicated in iron metabolism/uptake (CirA, FecA, FepA) and protein degradation (OmpT)	44
	sRNA103	trans-encoded ncRNA activates expression of the transcriptional activator gene fimZ	Expression of type 1 fimbriae and the filament protein EspA of the T3SS in EHEC	48
	RyhB	trans-encoded ncRNA acts through direct base-pairing with target mRNAs, Hfq-dependent	Regulation of iron metabolism and other iron-containing proteins, production of siderophores	121
	5′-UTR-chuA	FourU RNA thermometer	Iron uptake in EPEC	132
	GidA	tRNA-modifying enzyme	Regulation of the cytotoxic necrotizing factor 1 (CNF1)	69
	VacC	tRNA-guanine glycolase	Enhances expression of the Shigella T3SS effectors IpaB, IpaC and IpaD, reduces amounts of VirG important for cell-to-cell spreading of EIEC	67
Salmonella	CsrABC	CsrA: RNA binding protein, CsrB/CsrC: CsrA-binding RNAs CsrA directly binds and stabilizes the flhDC and the fliA transcript	Regulation of expression of type 1 and Pef fimbrae, regulation of SPI-1 gene expression via translational repression of the SPI-1 regulator HilD, control of motility and biofilm formation, regulation of c-di-GMP synthesis	49,50,54
	IsrJ	unknown	Regulation of invasion and SPI-1 effector translocation	65
	IsrM	trans-encoded ncRNA reduces mRNA stability by binding to the 5′-UTR of its target mRNA	Control of SPI-1 gene expression by regulation of the global SPI-1 regulator HilE and the effector SopA	66
	LesR-1	antisense RNA interacts with the 3′-UTR of PSLT047 modulating translation rate	Control of virulence in mice	87
	RydC	trans-encoded ncRNA folds as a pseudoknot and interacts with Hfq	Control of the yejABEF operon which interferes with MHCI presentation, counteracts antimicrobial peptides and promotes survival and proliferation within the host. Control of the curli adhesin through repression of the major curli regulator CsgD;	44
	PinT/STnc440	trans-encoded ncRNA Hfq-dependent	Repression of SPI-2 genes and SPI-1 effector genes (sopE, sopE2), manipulation of host cell pathways to promote replication, important for the transition from the extracellular to the intracellular state, influences regulators of the JAK-STAT signaling pathway (e.g. STAT3), IL-8 production, and mitochondria localization and functions. Colonization in pigs and cattle	65,79,85
	RaoN	trans-encoded ncRNA	Induced under oxidative stress and nutrient limitation, important for survival in macrophages, controls expression of the lactate dehydrogenase gene ldhA	135
	RyhB-1, RyhB-2	trans-encoded ncRNAs Hfq-dependent	Iron homeostasis, oxidative and acidic stress, intracellular growth, redundant functions but RyhB-2 targets some motility genes (flgJ, cheY, and fliF) that are not regulated by RyhB1, and RyhB1 influences safA, acnB expression but not RyhB2	129,130
	SgrS	trans-encoded ncRNA Hfq-dependent	Resistance against phosphosugar stress	60,61
	GidA, MnmE	tRNA-modifying enzymes	Active induction of the T3SS genes invAEG, spaPQ and prgHJ. Control of the oxidoreductase YghA and thiol peroxidase Tpx Important for cell invasion, survival in macrophages and mouse virulence	68
	PNPase	Polynucleotide phosphorylase	Influence on the expression of the AgfA fibers, the SPI-1 invasion genes, as well as the spv and SPI-2 genes important for macrophage survival, controls the ncRNAs RyhB, SgrS, CsrB and CsrC	4,12,73,90,105
Shigella	CsrABC	CsrA: RNA binding protein, CsrB/CsrC: CsrA-binding RNAs	Regulation of attachment and invasion via control of the regulators VirF and VirB	55
	RnaG	antisense RNA to icsA, expression leads to premature termination of icsA transcription	Control of host colonization by repression of the IcsA invasion protein	62,63
	RyhB	trans-encoded ncRNA acts through direct base-pairing with target mRNAs, Hfq-dependent	Regulation of invasion and cell-to-cell spreading via control of VirB synthesis, acid resistance	123-125,127
	5′-UTR-shuA	FourU RNA thermometer	Iron uptake	126,132
	RNase R	ribonuclease	Synthesis of the T3SS effector proteins IpaB, IpaC and IpaD	72
	VacC	tRNA-guanine glycolase tRNA-modifying enzyme	Enhances expression of the Shigella T3SS effectors IpaB, IpaC and IpaD, reduces amounts of VirG important for cell-to-cell spreading	67
Yersinia	CsrABC	CsrA: RNA binding protein, CsrB/CsrC: CsrA-binding RNAs	Contribute to attachment and invasion via regulation of global regulators of invasion factors (e.g.(e.g., InvA, PsaA/pH6 antigen), Control of biofilm formation and motility Regulation of c-di-GMP synthesis	26,35
	Ysr29	trans-encoded ncRNA	Specific to the Y. pseudotuberculosis strain IP32953, important for the virulence in a mouse model of Yersiniosis, represses synthesis of glutathione-S transferase (GST) and activates production of RpsA, OmpA and GroEL	5,6,134
	Ysr35	trans-encoded ncRNA	Survival in a Yersiniosis mouse model	5
	Ysr141	trans-encoded ncRNA acts through base-pairing with the yopJ 5′-UTR	Regulation of T3SS components (YopE, YscF, YopK, YopJ) and the T3SS activator LcrF	5,117
	RyhB-1, RyhB-2	Hfq-dependent trans-encoded ncRNA	Iron homeostasis	122,131
	YopD/LcrH	YopD: RNA-binding protein,interacts with 30S particle of the ribosome LcrF: YopD chaperone YopD-LcrH protein complex binds to the 5′-UTR of target transcripts preventing translation and/or enhancing degradation	Important for T3SS, Yop effector injection, survival of phagocyte attacks	96,97,99
	LcrQ (YscM1, YscM2)	cooperates with YopD-LcrH complex	Important for T3SS, Yop effector injection, survival of phagocyte attacks	98
	5′-UTR-lcrF	FourU RNA thermometer	Control of pathogenesis (T3SS regulation and Yop effector secretion), survival of phagocyte attacks	94,95
	SsrA (tmRNA) /SmpB	SsrA: aminoacylated SsrA RNA mimicking a tRNA or a mRNA SmpB: RNA binding protein that interacts with SsrA	Important for virulence (regulation of T3SS expression, survival of phagocyte attacks), activation of LcrF expression	114
	YbeY	single-strand specific endoribonuclease	Important for virulence (regulation of T3SS expression, survival of phagocyte attacks), regulation of LcrF expression	110
	PNPase RNase E	Ribonucleases part of the degradosome, regulated RNA degradation	Influence on the expression and activity of T3SS, Yop effector injection into host cells, survival of phagocyte attacks. Degradation of the hmsT and pgaABCD transcript, allows rapid regulation of c-di-GMP synthesis and biofilm production	100-103