TABLE 3.

Iron uptake systems in S. pneumoniae strains R6 and TIGR4^a

Strain	Cluster no.b	Cluster namec	Gene productd	Locus no.e	Sequence tagf	Enzymatic activityg
R6	1	None	ABC-MSP	SPR0220	MLVFM	Permease
			ABC-MSP	SPR0221	MERKK	Permease
			ABC-NBD	SPR0222	MSEIE	ATPase
			ABC-SBPx	SPR0223	MNIEG	SideroBP
	2	None	ABC-SBP	SPR0934	MKNKF	SideroBP
			ABC-MSP	SPR0935	MHAKM	Permease
			ABC-MSP	SPR0936	MQNLI	Permease
			ABC-NBD	SPR0938	MKGLW	ATPase
	3	Fat	FatD	SPR1684	MKGRG	Permease
			FatC	SPR1685	MQTKS	Permease
			FecE	SPR1686	MKLEN	ATPase
			FatB	SPR1687	MKTSL	SideroBP
TIGR4	1	Pit	PitA	SP0241	?	Permease
			PitD	SP0241	?	Permease
			PitB	SP0242	MSEIK	ATPase
			PitC	SP0243	MKKKW	SideroBP
	2	Pit2	PiaA	SP1032	MKNKF	SideroBP
			PiaB	SP1033	MHAKM	Permease
			PiaC	SP1034	MQNLI	Permease
			PiaD	SP1035	MKGLW	ATPase
	3	Pit1	PiuB	SP1869	MKGRG	Permease
			PiuC	SP1870	MQTKS	Permease
			PiuD	SP1871	MKLEN	ATPase
			PiuA	SP1872	MKTSL	SideroBP

^aThe iron transporter determinants in S. pneumoniae R6 and TIGR4 are organized as three clusters, each consisting of four genes (two heterodimer-forming permease genes, one ABC ATPase gene, and one iron carrier-binding protein gene).

^bThe three iron transporter clusters are designated clusters 1, 2, and 3 in both R6 and TIGR4 in the order of their proximity to the sequencing origin. The three gene clusters preserve synteny between the R6 and TIGR4 genomes that extends to the order of functions of the individual genes within each cluster.

^cThe strongly up-regulated genes in the ritR knockout correspond to R6 cluster 3, where they are annotated as FatD and FatB in GenBank accession no. AY-312585 and as piuB and piuA by Brown et al. (6). Clusters 2 and 3 in the TIGR4 sequence correspond to Pit2 and Pit1, respectively, or to pia and piu, respectively, as described previously (5, 6).

^dR6 clusters 1 and 2 were designated with ABC prefixes as annotated in GenBank accession no. NC-003028 for TIGR4 and NC-003098 for R6. R6 cluster 3 FatDCB and FecE were named based on their amino acid sequence similarity to V. anguillarum iron transporter elements described by Tettelin et al. (52). TIGR4 clusters 2 and 3 were named PiaABCD and PiuBCDA, respectively (6).

^eAnnotations in GenBank assigned successive numbers to ORF sequences deduced from the DNA sequence data. For R6 the numbers for ORFs range from 1 to 2,046, whereas for TIGR4 the numbers range from 1 to 2,240, and the difference is presumed to be due to pathogenicity islands (6) in the latter organism.

^fThe first five amino acids encoded by each iron transporter ORF was obtained from GenBank and is listed for possible use for verification.

^gThe annotation “SideroBP” indicates siderophore binding protein, as reported in the cited GenBank files. Experimental data reported by Tai et al. (50 ) suggest that the siderophore binding proteins in S. pneumoniae actually bind hemin.