Streptococcus agalactiae 1311 Experimental study of early-onset infection suggests that this bacteria to invade fetal epithelial and endothelial cells and certain macrophages and the mortality rates for early-onset is 4-6%. This invasion is confirmed to play important role in its pathogenesis through the ability of S. agalactiae in the monkey model. Ability to invade and transcytose, this bacteria can enter into the respiratory tract causing pneumonia or further into the blood causing septicemia. Bloodstream enables this bacteria to reach different sites of body causing meningitis and osteomyelitis (MicrobeWiki: S. agalactiae). Group B streptococcus (GBS) infection Passive immunization with antibodies has been shown to be protective in mice (Erdogan et al., 2002). S. agalactiae colonizes in the body of some animals, including cow, sheep, and humans without causing any harm. The habitat of this microorganism is largely confined to the intestine and vagina in human and the mammary gland of cows and sheep. This microorganism also colonizes in the genital and/or intestinal tract of about 10-30% of pregnant women. However, some can actually cause diseases in their neonates or immunocompromised mammals. Monkeys and mice can be used as a model of disease (MicrobeWiki: S. agalactiae). S. agalactiae is a member of the gastrointestinal normal flora in some humans and can spread to secondary sites - including the vagina in 10-30% of women. This is of clinical importance: S. agalactiae can be transferred to a neonate passing through the birth canal and can cause serious group B streptococcal infection. In the western world, S. agalactiae is the main cause of bacterial septicemia of the newborn, which can lead to death or long-term sequelae. S. agalactiae invade via alveolar and pulmonary epithelial cells; newborns are especially succeptible to infection because they lack alveolar macrophages to prevent invasion. Newborn GBS disease is separated into early-onset disease occurring on living days 0-7 and late-onset disease which starts on days 7-90. Early-onset septicemia is more prone to be accompanied by pneumonia, while late-onset septicimia is more often accompanied by meningitis. S. agalactiae neonatal meningitis does often not present with the hallmark sign of adult meningitis, a stiff neck; rather, it presents with nonspecific symptoms such as fever, vomiting and irritability and can consequently lead to late diagnosis. Hearing loss can be a long-term sequelae of GBS-meningitis. Infection with GBS is the cause of some instances of stillbirth (Wiki: S. agalactiae). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 licensed Group B streptococcal infection human vaccine Generic Unknown VO_0001375 Conjugate vaccine Licensed A generic representation of vaccines utilized to prevent Group B streptococcal (GBS) infection in humans, typically consisting of GBS polysaccharides chemically linked to a protein carrier to enhance immunogenicity. These conjugate vaccines are designed to induce protective immunity against GBS, especially in populations at risk such as pregnant women and newborns. S. agalactiae BipA Protein Vaccine VO_0004200 Subunit vaccine Research Intraperitoneal injection (i.p.) Complete Freund's adjuvant on day 1, incomplete Freund's adjuvant on day 35 (Santi et al., 2009). Intraperitoneal injection (i.p.) Recombinant BipA protein Recombinant protein preparation CD‐1 Active mouse maternal immunization.A maternal immunization/neonatal pup challenge model of GBS infection was used to verify the protective efficacy of BibA protein in mice. CD‐1 female mice (6–8 weeks old) were immunized intraperitoneally on days 1 (complete Freund’s adjuvant), 21, and 35 (incomplete Freund’s adjuvant) with either PBS or 20 μg of recombinant protein and were then bred 3 days after the last immunization (Santi et al., 2009). Immunization of mice with recombinant BibA conferred protection to 69% of the challenged pups (Santi et al., 2009). Within 48 h of birth, pups were injected intraperitoneally with a dose of GBS strain 3050 that would be lethal to 90% of the population, corresponding to 3 x 10^4 colony‐forming units (CFU). Survival of pups was monitored for 3 days after challenge (Santi et al., 2009). S. agalactiae BPS Protein Vaccine VO_0004050 Subunit vaccine Research subcutaneous injection Aluminum phosphate (Adju-Phos; Axell Accurate Chemical & Scientific Corp.) (Erdogan et al., 2002). subcutaneous injection Recombinant BPS Recombinant protein preparation BALB/c Four-week-old female BALB/c (H-2d) mice were immunized with recombinant BPS protein on days 1, 3, 6, and 27 (30 μg/dose) by the subcutaneous route with aluminum phosphate as the adjuvant (Erdogan et al., 2002). When the immunized animals were challenged with strain Compton R, approximately 88% of the vaccinated animals survived whereas mice in the control group were not protected (78% lethality) (Erdogan et al., 2002). Groups of immunized and control animals were challenged on day 37 with an inoculum of the streptococcal strain Compton R corresponding to the 80% lethal dose (LD80; 5 × 10^8 bacteria/ml) in nonimmunized mice, and mortality was recorded daily (Erdogan et al., 2002). S. agalactiae Rib Protein Vaccine VO_0004051 Subunit vaccine Research subcutaneous injection 0.1 ml of complete Freund’s adjuvant. subcutaneous injection Purified Rib protein Recombinant protein preparation C3H/HeN Male C3H/HeN mice, 7 to 13 weeks old, were immunized subcutaneously with 25 μg of pure protein (Rib or bovine serum albumin [BSA]) in 0.1 ml of phosphate-buffered saline (PBS) mixed with 0.1 ml of complete Freund’s adjuvant. Four weeks later the mice were given boosters of the same amount of protein with incomplete Freund’s adjuvant (Larsson et al., 1996). Vaccination of mice with the Rib protein protected against two strains of capsular type III and two strains of type II (Larsson et al., 1996). Two weeks after the booster, the mice were injected intraperitoneally (i.p.) with a 90% lethal dose (LD90) of log-phase bacteria, diluted in 0.5 ml of Todd-Hewitt broth. The LD90 for the different strains varied between 10^6 and 10^7 bacteria, as determined in preliminary experiments (Larsson et al., 1996). S. agalactiae Sip Protein Vaccine VO_0004052 Subunit vaccine Research subcutaneous injection 20 μg of QuilA adjuvant subcutaneous injection Recombinant Sip protein. Recombinant protein preparation CD-1 Mice were injected s.c. three times at 3-week intervals with either 20 μg of purified recombinant Sip protein in 0.1 ml of PBS mixed with 20 μg of QuilA adjuvant (Cedarlane), 15 μg of formaldehyde-killed GBS WC with 20 μg of QuilA as positive controls, or 20 μg of QuilA in PBS as a negative control (Brodeur et al., 2000). Immunization with the recombinant Sip protein efficiently protected CD-1 mice against deadly challenges with six GBS strains of serotypes Ia/c, Ib, II/R, III, V, and VI (Brodeur et al., 2000). To evaluate the challenge dose required for each GBS strain, between 10^4 and 10^8 CFU/mouse was injected i.p. into groups of CD-1 female mice (Brodeur et al., 2000). BipA Streptococcus agalactiae 255961211 CDD:310807 CDD:114603 CDD:307064 1311 ? BibA 9.74 59842.07 648 MucBP domain; pfam06458 >ACU44481.1 BibA [Streptococcus agalactiae] MNNNEKKVKYFLRKTAYGLASMSAAFIVCSGIVNTPTVSADSPDTLKVEKLGKLKDVKSVHELTPISIPN ELKGAKEQALSSIISHPNITNSEVDKLASDYSFRINTSNDVNDVKRLLNEFYNAVARKQLDTNSADYRSK IDNISTTGLAIALEAKEIYEANKSILPHRYKDSVGTYVNSFEERRSPGKFNIWNGQEGFNAAQKLLEDVK KLLLELQNLTKNNKPNIQVPKQAPTEAAKPALSPEALTRLTTWYNQAKDLLKDDQVKDKYVDILSVQKAV DQAYDHVEEGKFITTDQANQLANKLRDALQSLELKDKKVAKPVAKGTYDVKYVDTEGKEVAKSRHFEGEE GAAFVTSAKEVAGYKLVRTEGAVSNVFTAGAQVRTYVYEKVAKPVAKGTYDVKYVDTEGKEVAKSRHFEG EEGAAFVTSAKEVAGYKLVRTEGAVSNVFTAGAQVRTYVYEKVKPEVKPDVKPEAKPEAKPEVKPDVKPE AKPEAKPEVKSDVKPEAKPEAKPEAKPEVKPDVKPEAKPEAKPATKKSVNTSGNLVAKKAIENKKYSKKL PSTGEAASPLLAIVSLIVMLSAGLITIVLKHKKN Protective antigen Mice immunized with BibA were protected against challenge by a GBS strain with high levels of surface exposure of the antigen [Ref1555:Santi et al., 2009]. rib Streptococcus agalactiae strain BM110 VO_0012403 1620648 CDD:309682 CDD:312387 CDD:323788 CDD:307064 1311 ? surface protein Rib 4.28 113797.43 1309 YSIRK type signal peptide; pfam04650 >AAC44468.1 surface protein Rib [Streptococcus agalactiae] MFRRSKNNSYDTLQTKQRFSIKKFKFGAASVLIGISFLGGFTQGQFNISTDTVFAAEVISGSAVTLNTNM TKNVQNGRAYIDLYDVKNGKIDPLQLITLNSPDLKAQYVIRQGGNYFTQPSELTTVGAASINYTVLKTDG SPHTKPDGQVDIINVSLTIYNSSALRDKIDEVKKKAEDPKWDEGSRDKVLISLDDIKTDIDNNPKTQSDI ANKITEVTNLEKILVPRIPDADKNDPAGKDQQVNVGETPKAEDSIGNLPDLPKGTTVAFETPVDTATPGD KPAKVVVTYPDGSKDTVDVTVKVVDPRTDADKNDPAGKDQQVNVGETPKAEDSIGNLPDLPKGTTVAFET PVDTATPGDKPAKVVVTYPDGSKDTVDVTVKVVDPRTDADKNDPAGKDQQVNVGETPKAEDSIGNLPDLP KGTTVAFETPVDTATPGDKPAKVVVTYPDGSKDTVDVTVKVVDPRTDADKNDPAGKDQQVNVGETPKAED SIGNLPDLPKGTTVAFETPVDTATPGDKPAKVVVTYPDGSKDTVDVTVKVVDPRTDADKNDPAGKDQQVN VGETPKAEDSIGNLPDLPKGTTVAFETPVDTATPGDKPAKVVVTYPDGSKDTVDVTVKVVDPRTDADKND PAGKDQQVNVGETPKAEDSIGNLPDLPKGTTVAFETPVDTATPGDKPAKVVVTYPDGSKDTVDVTVKVVD PRTDADKNDPAGKDQQVNVGETPKAEDSIGNLPDLPKGTTVAFETPVDTATPGDKPAKVVVTYPDGSKDT VDVTVKVVDPRTDADKNDPAGKDQQVNVGETPKAEDSIGNLPDLPKGTTVAFETPVDTATPGDKPAKVVV TYPDGSKDTVDVTVKVVDPRTDADKNDPAGKDQQVNVGETPKAEDSIGNLPDLPKGTTVAFETPVDTATP GDKPAKVVVTYPDGSKDTVDVTVKVVDPRTDADKNDPAGKDQQVNVGETPKAEDSIGNLPDLPKGTTVAF ETPVDTATPGDKPAKVVVTYPDGSKDTVDVTVKVVDPRTDADKNDPAGKDQQVNVGETPKAEDSIGNLPD LPKGTTVAFETPVDTATPGDKPAKVVVTYPDGSKDTVDVTVKVVDPRTDADKNDPAGKDQQVNVGETPKA EDSIGNLPDLPKGTTVAFETPVDTATPGDKPAKVVVTYPDGSKDTVDVTVKVVDPRTDADKNDPAGKDQQ VNGKGNKLPATGENATPFFNVVALTIMSSVGLLSVSKKKED Protective antigen Vaccination of mice with the Rib protein protected against two strains of capsular type III and two strains of type II, and vaccination with the alpha protein protected against one strain of type II and one strain of type Ib [Ref1518:Larsson et al., 1996]. sar5 Streptococcus agalactiae Compton R VO_0012393 5327234 CDD:273479 CDD:283989 CDD:273478 GOA:Q9XAS7 InterPro:IPR001899 InterPro:IPR005877 UniProtKB/TrEMBL:Q9XAS7 1311 ? BPS protein 4.92 96916.55 1045 Gram-positive signal peptide, YSIRK family; TIGR01168 >CAB46338.1 BPS protein [Streptococcus agalactiae] MFRQYNFEKGLNFSIRKFSVGIASVAIGSLLFILPQVLADETTSVTSATTPTGVTTTDANLVNPNNSTPT STNRSATSTQGSNLSNTSEIIKPATLAATSPTTDNVAPSVDKRTYATSGDWTLQNPYADSVRNKNISPSV RHESFKSAETTVVRHDNSTVKVTATITPVEGNDEGSGILTNGGNQSEYKATSEMFVGNVDPAKIPALGVY TQPGRTEGGSKLSDKLNFNGKAPSTILTLKFDKAVTDPIIDLSGVGGNARLSFTETVMENGKIVEKFDYA RGSYNSTFFDGITPGISLEKASSGVNLTVTANTVDVTDKNTFNESVVNPSDEDFVNGPDRTPDAVPAGTG SIRLKGTFTDASFKLYHQAVPSTAFSKEKYHTGDGYYNSIANVRPTVVKPDSINGLNKHASDVIDYKISD NNDISNDDLLRLSVRLQNPRGSVVVNYIDTEGNIIGTEYKDTTDAIPGTHYNTAESSGDLNSDATVERPS TITKDGKVYDLVAENITVPVGKVNSDGTLATNGSSFNYGTDAASAEVAEGTKSVIYVISIKQESKGNVHA RYVILGTETELASAKTVKSEAPIDEAYSDKAPATLEKDGKLYEFVHVRDNKGDAPADGKVTEQDQTITYE YVEVPKGRVVVDYVIEGTATKPKDTYVDTPTAYIRDKEGQAIPYNTAENDSEKPLLLDKDGIKYELVSIQ EGSAAEKGTLREGEQHVVYQYRKVVEVPSVKVGNVHARYVILGTETELASAKTVKSEAPIDEAYSDKAPA TLEKDGKLYEFVHVRDNKGDAPADGKVTEQDQTITYEYKLKKDDADAVGNVVINYVDETGNVIKKPILDT HESKVGTPYDTTDYKFAEIKFNGKIYKLVSAKTMGNEFGKVTEGTTEVTYVYRESVKSTLPKETGISIPS ESESPKFISTQTTENRPNKGVLTSSKNPTNKSVLPTTGEESNRILGVVGITLVATTATLAASSLKRRKN Protective antigen Immunization of mice with recombinant BPS protein by the subcutaneous route produced an efficient antigen-specific response, and immunized animals survived challenge with a lethal dose of a virulent strain [Ref1506:Erdogan et al., 2002]. Sip Streptococcus agalactiae A909 VO_0012402 3685788 76788047 SAK_0065 CP000114 YP_328758 CDD:212030 CDD:331378 205921 47330 48634 + group B streptococcal surface immunogenic protein 8.59 40547.64 434 Lysine Motif is a small domain involved in binding peptidoglycan; cd00118 >NC_007432.1:47330-48634 Streptococcus agalactiae A909, complete genome AATGAAAATGAATAAAAAGGTACTATTGACATCGACAATGGCAGCTTCGCTATTATCAGTCGCAAGTGTT CAAGCACAAGAAACAGATACGACGTGGACAGCACGTACTGTTTCAGAGGTAAAGGCTGATTTGGTAAAGC AAGACAATAAATCATCATATACTGTGAAATATGGTGATACACTAAGCGTTATTTCAGAAGCAATGTCAAT TGATATGAATGTCTTAGCAAAAATTAATAACATTGCAGATATCAATCTTATTTATCCTGAGACAACACTG ACAGTAACTTACGATCAGAAGAGTCATACTGCTACTTCAATGAAAATAGAAACACCAGCAACAAATGCTG CTGGTCAAACAACAGCTACTGTCGATTTGAAAACCAATCAAGTTTCTGTTGCAGACCAAAAAGTTTCTCT CAATACAATTTCGGAAGGTATGACACCAGAAGCAGCAACAACGATTGTTTCGCCAATGAAGACATATTCT TCTGCGCCAGCTTTGAAATCAAAAGAAGTATTAGCACAAGGGCAAGCTGTTAGTCAAGCAGCAGCTAATG AACAGGTATCACCAGCTCCTGTGAAGTCGATTACTTCAGAAGTTCCAGCAGCTAAAGAGGAAGTTAAACC AACTCAGACGTCAGTCAGTCAGTCAACAACAGTATCACCAGCTTCTGTTGCCGCTGAAACACCAGCTCCA GTAGCTAAAGTAGCACCGGTAAGAACTGTAGCAGCCCCTAGAGTGGCAAGTGTTAAAGTAGTCACTCCTA AAGTAGAAACTGGTGCATCACCAGAGCATGTATCAGCTCCAGCAGTTCCTGTGACTACGACTTCAACAGC TACAGACAGTAAGTTACAAGCGACTGAAGTTAAGAGCGTTCCGGTAGCACAAAAAGCTCCAACAGCAACA CCGGTAGCACAACCAGCTTCAACAACAAATGCAGTAGCTGCACATCCTGAAAATGCAAGGCTCCAACCTC ATGTTGCAGCTTATAAAGAAAAAGTAGCGTCAACTTATGGAGTTAATGAATTCAGTACATACCGTGCGGG AGATCCAGGTGATCATGGTAAAGGTTTAGCAGTTGACTTTATTGTAGGTAAAAACCAAGCACTTGGTAAT GAAGTTGCACAGTACTCTACACAAAATATGGCAGCAAATAACATTTCATATGTTATCTGGCAACAAAAGT TTTACTCAAATACAAATAGTATTTATGGACCTGCTAATACTTGGAATGCAATGCCAGATCGTGGTGGCGT TACTGCCAACCACTATGACCACGTTCACGTATCATTTAACAAATA >YP_328758.1 group B streptococcal surface immunogenic protein [Streptococcus agalactiae A909] MKMNKKVLLTSTMAASLLSVASVQAQETDTTWTARTVSEVKADLVKQDNKSSYTVKYGDTLSVISEAMSI DMNVLAKINNIADINLIYPETTLTVTYDQKSHTATSMKIETPATNAAGQTTATVDLKTNQVSVADQKVSL NTISEGMTPEAATTIVSPMKTYSSAPALKSKEVLAQGQAVSQAAANEQVSPAPVKSITSEVPAAKEEVKP TQTSVSQSTTVSPASVAAETPAPVAKVAPVRTVAAPRVASVKVVTPKVETGASPEHVSAPAVPVTTTSTA TDSKLQATEVKSVPVAQKAPTATPVAQPASTTNAVAAHPENARLQPHVAAYKEKVASTYGVNEFSTYRAG DPGDHGKGLAVDFIVGKNQALGNEVAQYSTQNMAANNISYVIWQQKFYSNTNSIYGPANTWNAMPDRGGV TANHYDHVHVSFNK Protective antigen Immunization with the recombinant Sip protein efficiently protected CD-1 mice against deadly challenges with six GBS strains of serotypes Ia/c, Ib, II/R, III, V, and VI [Ref1517:Brodeur et al., 2000]. Brodeur et al., 2000 journal Brodeur BR, Boyer M, Charlebois I, Hamel J, Couture F, Rioux CR, Martin D 2000 68 10 5610-5618 Infection and immunity Brzychczy-Wloch et al., 2013 journal Brzychczy-Wloch M, Gorska S, Brzozowska E, Gamian A, Heczko PB, Bulanda M 2013 349 1 61-70 FEMS microbiology letters Erdogan et al., 2002 journal Erdogan S, Fagan PK, Talay SR, Rohde M, Ferrieri P, Flores AE, Guzmán CA, Walker MJ, Chhatwal GS 2002 70 2 803-811 Infection and immunity Grenningloh et al., 2008 journal Grenningloh R, Darj A, Bauer H, zur Lage S, Chakraborty T, Jacobs T, Weiss S 2008 67 6 594-602 Scandinavian journal of immunology Kvam et al., 2011 journal Kvam AI, Mavenyengwa RT, Radtke A, Maeland JA 2011 18 8 1365-1370 Clinical and vaccine immunology : CVI Larsson et al., 1996 journal Larsson C, Stålhammar-Carlemalm M, Lindahl G 1996 64 9 3518-3523 Infection and immunity Li et al., 2016 journal Li W, Wang HQ, He RZ, Li YW, Su YL, Li AX 2016 55 737-746 Fish & shellfish immunology Liu et al., 2013 journal Liu G, Zhang W, Lu C 2013 69 3 223-231 Pathogens and disease MicrobeWiki: S. agalactiae website http://microbewiki.kenyon.edu/index.php/Streptococcus_agalactiae Pannaraj et al., 2008 journal Pannaraj PS, Kelly JK, Rench MA, Madoff LC, Edwards MS, Baker CJ 2008 26 4 502-508 Vaccine Santi et al., 2007 journal Santi I, Scarselli M, Mariani M, Pezzicoli A, Masignani V, Taddei A, Grandi G, Telford JL, Soriani M 2007 63 3 754-767 Molecular microbiology Santi et al., 2009 journal Santi I, Maione D, Galeotti CL, Grandi G, Telford JL, Soriani M 2009 200 4 564-570 The Journal of infectious diseases Santillan et al., 2011 journal Santillan DA, Rai KK, Santillan MK, Krishnamachari Y, Salem AK, Hunter SK 2011 205 3 249.e1-8 American journal of obstetrics and gynecology Suvorov et al., 2010 journal Suvorov AN, Grabovskaia KB, Leont'eva GF, Meringova LF, Koroleva IN, Duplik NV, Totolian AA 2010 2 44-50 Zhurnal mikrobiologii, epidemiologii, i immunobiologii Wiki: S. agalactiae website http://en.wikipedia.org/wiki/Streptococcus_agalactiae Xue et al., 2010 journal Xue G, Yu L, Li S, Shen X 2010 58 2 202-210 FEMS immunology and medical microbiology Yang et al., 2007 journal Yang HH, Madoff LC, Guttormsen HK, Liu YD, Paoletti LC 2007 75 7 3455-3461 Infection and immunity