Table I. Classification of known bacterial protective antigens based on their functional and structural features. References are provided as supplemental material.

Functional classes and subclasses		Antigens	%ID	Associated Pfam domains and clans
Flagellins		Flagellins from P. aeruginosaS1, E. coliS2, C. jejuniS3, H. pyloriS4	9–41%	PF00669, Flagellin_N, PF00700, Flagellin_C
ompa		C3389 from E. coliS5, P6 from H. influenzaeS6, Omp16 from B. abortusS7, OmpF from P. aeruginosaS8	16–32%	PF00691, OmpA
Toxins	Pore-forming toxins	Pneumolysin from S. pneumoniaeS9, Streptolysin O from S. pyogenesS10, Listeriolysin O from L. monocytogenesS11	38–43%	PF01289, Thiol_cytolysin
		Alpha-toxinS12 and Panton-Valentine Leukocidin FS13 from S. aureus	24%	PF07968, Leukocidin
		RTX-I and RTX-II toxins from A. pleuropneumoniaeS14, Cya from B. pertussisS15, Hemolysin from E. coliS16	23–55%	PF00353. HemolysinCabind PF02382. RTX.
	Ribosyl transferases	Diphteriae toxin from C. diphtheriaeS17, Pertussis toxin from B. pertussisS17, Cholera toxin from V. choleraeS18	7–11%	CL0084. ADP-ribosyl
	Neurotoxins	Tetanus toxin from C. tetaniS19, Botulinum toxin from C. botulinumS20	33%	PF01742. Peptidase_M27 PF07951. Toxin_R_bind_C. PF07953. Toxin_R_bind_N.
	Glycosyltransferases	Toxin A and Toxin B from C. difficileS21	47%	PF11713. Peptidase_C80. PF12919. TcdA_TcdB. PF12920. TcdATcdB_pore
	Binary toxins	Protective antigen from B. anthracisS22, C2 toxin from C. botulinumS20, Iota toxin component Ib from C. perfringensS23	26–37%	PF03495. Binary_toxB
Extracellular enzymes	proteases	C5a peptidases from S. agalactiae and S. pyogenesS24,S24a, SpyCEP from S. pyogenesS25, PrtA from S. pneumoniaeS26, NMB1969 from N. meningitidisS27	9–29%	PF00082. Peptidase_S8
	Hydrolases with papain-like fold	P60 from L. monocytogenesS28, NMB2001 from N. meningitidisS29, PcsB from S. pneumoniaeS30, SpeB from S. pyogenesS31	6–21%	CL0125. Peptidase_CA
	Hydrolases with trypsin-like fold	HtrA from H. influenzaeS32, CT823 from C. trachomatisS33	x%	PF00089. Trypsin
	5′ nucleotidases	NucA from H. influenzaeS34, Spy0872 from S. pyogenesS35	18%	PF02872. 5_nucleotid_C PF00149. Metallophos.
Iron uptake and other transport systems	heme binding proteins	IsdA and IsdB from S. aureusS36	10–32%	PF05031. NEAT
	Tonb dependent receptors	IroN, FyuA, IreA and IutAS37 from E. coli, TbpA from P. haemolyticaS38	5–11%	PF07715. Plug PF00593. TonB_dep_Rec
	Other transport proteins	OmpP1 from H. influenzaeS39, OmpP1 from N. meningitidisS40	23%	PF03349. Toluene_X
Solute binding	Transferrin binding protein-like proteins	Heparin binding protein GNA2132 from N. meningitidisS41, TbpB from P. haemolyticaS38	8–23%	PF01298. Lipoprotein_5
Proteins	Other solute binding proteins	P39 from B. melitensisS42, CjaA from C. jejuniS43, GNA1946 from N. meningitidisS29, PotD from S. pneumoniaeS44, ArtJ from C. trachomatisS45	6–58%	CL0177. PBP
Secretion and export systems	secretion system effector c-like proteins	SseC from Y. pseudotuberculosisS46, and IpaB from ShigellaS47	19%	PF04888. SseC
	Lcrv-like proteins	LcrV from Y. enterocoliticaS48, LcrV from Y. pestisS49, and PcrV from P. aeruginosaS50	39–95%	PF04792. LcrV
	Type iii secretory chaperones	YerA from Y. pestisS51, CT043 from C. trachomatisS52	24%	PF05932. CesT
Putative adhesins and invasins	fibronectin-binding proteins	FnbA from S.aureusS53, Fnz from S.equiS54, and Sfb from S.pyogenesS55	10–25%	PF02986. Fn_bind.
	Proteins with cnab domain	Pili subunits from S. pyogenesS56, S. agalactiaeS57, and S. pneumoniaeS58, CnaS59, SdrD and SdrES60 from S. aureus	10–58%	PF05738. Cna_B
	Proteins with uncharacterized multiple internal repeats	SdrD and SdrES60 from S. aureus, SAN_1485 from S.agalactiaeS61	17–55%	PF10425. SdrG_C_C
		RibS62 and C protein alpha antigenS63 from S.agalactiae	48%	PF08829. AlphaC_N PF08428. Rib
	Others	NadAS41 and NhhAS64 from N. meningitidis, UspA1 and UspA2 from M. catarrhalisS65, YadA and YadC from Y. pestisS66, C4424 from E. coliS67	8–42%	PF03895. YadA
		BrkAS68 and PertactinS69 from B. pertussis, Hap from H. influenzaeS70, NMB1998 from N. meningitidisS71	11–31%	PF03212. Pertactin
		PspC from S. pneumoniaeS72, IgA-binding beta antigen from S.agalactiaeS73	27%	PF05062. RICH
Proteins with other binding domains	lysm domain containing proteins	P60 from L. monocytogenesS28, Sip from S.agalactiaeS74, Intimin from E. coliS75	7–11%	PF01476. LysM
	Streptococcal histidine triad proteins	PhtA, PhtB and PhtDS76 from S. pneumoniae	32–87%	PF04270. Strep_his_triad