Disease relevance of aroA

• Protective immunity evoked by oral administration of attenuated aroA Salmonella typhimurium expressing cloned streptococcal M protein [1].
• A Salmonella typhimurium aroA mutant has been used as a live carrier to immunize mice against tetanus [2].
• Oral immunization of mice with attenuated Salmonella typhimurium aroA expressing a recombinant Mycoplasma hyopneumoniae antigen (NrdF) [3].
• Mice immunized intravenously 10 days earlier (but not those immunized 2 months earlier) with an attenuated Salmonella typhimurium SL3261 aroA live vaccine and tested for delayed-type hypersensitivity by injection of crude Salmonella extracts in the footpad can die within 24 to 48 h of an unexplained allergic reaction [4].
• We constructed an oral live vaccine based on the attenuated aroA mutant Salmonella enterica serovar Typhimurium strain SL3261 expressing outer membrane proteins F and I (OprF-OprI) from Pseudomonas aeruginosa and investigated it in a mouse model [5].

High impact information on aroA

• The aroA strain of S. typhimurium SL3261 was transformed with a low-copy plasmid vector pMK207, which contains the cloned gene spm5 encoding streptococcal M protein, the major virulence factor of these organisms [1].
• Mice were immunized orally with S. typhimurium aroA mutants either that expressed the lpf operon (phase-on variant) or in which the entire lpf operon had been removed by deletion [6].
• Oral infection of germ-free mice with Salmonella typhimurium aroA- caused a twofold to threefold increase in M cell numbers, crypt depth, and enterocyte migration rate after 7 days [7].
• Complete nucleotide sequence of the aroA gene from Salmonella typhi encoding 5-enolpyruvylshikimate 3-phosphate synthase [8].
• Typhimurium or aroA, invH and ssaV mutant derivatives were associated with late endosome markers [9].

Chemical compound and disease context of aroA

• Igh-6(-/-) mice immunized with a live, attenuated aroA Salmonella enterica serovar Typhimurium vaccine strain showed impaired long-term acquired resistance against the virulent serovar Typhimurium strain C5 [10].
• Toxicity of lipopolysaccharide and of soluble extracts of Salmonella typhimurium in mice immunized with a live attenuated aroA salmonella vaccine [4].
• The major soluble cuticular glycoprotein of lymphatic filariae, gp29, has been expressed in the Salmonella typhimurium aroA aroD live vaccine strain BRD509 [11].
• Cellular and humoral immune responses to parenteral vaccination with an aromatic-defined (aroA) Salmonella typhimurium and to oral challenge with the S. typhimurium parent strain were examined in pigs [12].
• Lambs sucking non-immunised ewes or ewes immunised 4-5 weeks before lambing with live attenuated, aromatic-dependent (aroA) Salmonella typhimurium (strain CS 332) were challenged orally at either 2, 4 or 7 days of age with virulent S. typhimurium (strain CS 94) at doses ranging from 10(9) to 10(13) colony forming units [13].

Biological context of aroA

• Antibody response and protection against challenge in mice vaccinated intraperitoneally with a live aroA O4-O9 hybrid Salmonella dublin strain [14].
• Three groups of six calves each, 5 to 7 weeks old, were orally vaccinated with the live aromatic-dependent delta aroA Salmonella dublin (O9,12) hybrid strain SL7103 with the O4,12-specifying rfb gene cluster from Salmonella typhimurium [15].
• In this study, we constructed strain KR21 (chi 4550 delta cya delta crp delta asd/pYA292asd(+)-toxC+) and compared it with BRD847 (aroA aroD/pnirB-toxC) for the ability to induce humoral and cellular immunity after a single oral or intravenous immunization in 3- to 4-week-old BALB/c mice [16].
• Transductants of the Aro- SerC- phenotype were treated with transducing phage grown on an S. typhimurium strain with an extensive deletion at aroA; selection for SerC+ yielded transductants, some of which were delta aroA [17].
• A S. dublin aroA vaccine conferred similar protection against wild-type S. dublin (approximately 300 x LD50) [18].

Anatomical context of aroA

• Delivery of the immunosuppressive antigen Salp15 to antigen-presenting cells by Salmonella enterica serovar Typhimurium aroA mutants [19].
• Animals immunized 2 to 3 months earlier with the S. typhimurium SL3261 aroA live vaccine were used as donors of serum, spleen cells, and mesenteric lymph node cells for naive recipients which were challenged orally with the virulent C5 strain [20].
• Strains harboring both aroA and purA mutations together were ineffective vaccines when administered orally or intravenously even though they persisted in the livers and spleens of the mice for long periods after intravenous infection [21].
• Natural killer cells mediate protection induced by a Salmonella aroA mutant [22].
• Here, we demonstrate that costimulation via the surface molecule CD28, but not antibody production by B cells, is required for clearance of attenuated aroA Salmonella enterica serovar typhimurium [23].

Associations of aroA with chemical compounds

• We found that whereas male (CBA/N x BALB/c)F1 mice (immunodefective) were more susceptible to wild-type S. typhimurium C5 than female littermates (immunocompetent), there was no difference in the response to the S. typhimurium aroA vaccine strain [24].
• SL3261 containing cloned aroA+ genes did not require exogenous phenylalanine, tryptophan, tryosine, p-aminobenzoic acid, or dihydroxybenzoic acid for growth in defined media [25].
• Tetracycline-sensitive mutants of the delta aroA his delta purHD derivative of strains Ty2 and CDC 10-80 may also be appropriate as live vaccines but have not been tested as such [17].
• Tetracycline-sensitive mutants of each of the three delta aroA his delta pur strains were isolated by selection for resistance to fusaric acid [17].
• Aromatic (aroA), galactose epimerase (galE), and diaminopimelic acid (dap) mutants of strain 3860C all resulted in much less fluid response, mucosal invasion, and mucosal damage compared with those by the parent organism [26].

Regulatory relationships of aroA

• In BALB/c mice, the rpoS aroA strain induced a systemic anti-LPS humoral response similar to that induced by the rpoS and aroA strains [27].
• Immunogenicity of a Salmonella typhimurium aroA aroD vaccine expressing a nontoxic domain of Clostridium difficile toxin A [28].

Other interactions of aroA

• IS200-VI is jointly transduced with aspC but not with aroA [29].
• Salmonella typhimurium aroA, htrA, and aroD htrA mutants cause progressive infections in athymic (nu/nu) BALB/c mice [30].
• In contrast, three different S. typhimurium aroA strains and an invA mutant of SL1344 did not induce significant fluid accumulation in the rabbit ileal loops [31].
• Expression of the TETC-14CDTA fusion protein was driven from the anaerobically inducible nirB promoter within attenuated Salmonella typhimurium BRD509 (aroA aroD) [28].
• Strains harboring any of these mutations were attenuated when tested in BALB/c mice. purE strains were less attenuated than aroA or purA strains [21].

Analytical, diagnostic and therapeutic context of aroA

• Vaccination of normal and TNFalphap55R knockout animals with S. typhimurium HWSH aroA showed that TNFalphap55R-/- mice, unlike TNFalphap55R+/+ mice, were not protected against a virulent S. typhimurium HWSH challenge [32].
• The results indicate that moderate immunosuppression does not markedly enhance susceptibility to S. typhimurium aroA live vaccines [24].
• The systemic humoral response induced by S. typhimurium rpoS, aroA and rpoS aroA vaccine candidates against S. typhimurium LPS was studied by ELISA [27].

References