Pseudomonas aeruginosa 287 P. aeruginosa infections are widely varied. The bacteria can colonize wounds and enter the blood stream, they can colonize the lungs, and they can also colonize the a scratched cornea. P. aeruginosa has a variety of virulence factors that contribute to its widely varied pathogenesis (Salyers and Whitt., 2002). Pseudomonas aeruginosa infection Most strains of P. aeruginosaare resistant to killing in serum alone, but the addition of polymorphonuclear leukocytes results in bacterial killing. Killing is most efficient in the presence of type-specific opsonizing antibodies, directed primarily at the antigenic determinants of LPS. This suggests that phagocytosis is an important defense and that opsonizing antibody is the principal functional antibody in protecting from P. aeruginosa infections. Once P. aeruginosa infection is established, other antibodies, such as antitoxin, may be important in controlling disease. Cell-mediated immunity does not seem to play a major role in resistance or defense against Pseudomonas infections (Textbook of Bacteriology). Pseudomonas aeruginosa is an opportunistic human pathogen. The burned mouse model is used to model pseudomonas infection in burn patients. For lung infections guinea pig and rat models are used. C. elegans is also a model used to study host-pathogen interactions (Salyers and Whitt., 2002). Pseudomonas aeruginosa is member of the Gamma Proteobacteria class of Bacteria. It is a Gram-negative, aerobic rod belonging to the bacterial family Pseudomonadaceae. Since the revisionist taxonomy based on conserved macromolecules (e.g. 16S ribosomal RNA) the family includes only members of the genus Pseudomonas which are cleaved into eight groups. Pseudomonas aeruginosa is the type species of its group. which contains 12 other members. Pseudomonas aeruginosa is an opportunistic pathogen, meaning that it exploits some break in the host defenses to initiate an infection. In fact, Pseudomonas aeruginosa is the epitome of an opportunistic pathogen of humans. The bacterium almost never infects uncompromised tissues, yet there is hardly any tissue that it cannot infect if the tissue defenses are compromised in some manner. It causes urinary tract infections, respiratory system infections, dermatitis, soft tissue infections, bacteremia, bone and joint infections, gastrointestinal infections and a variety of systemic infections, particularly in patients with severe burns and in cancer and AIDS patients who are immunosuppressed. Pseudomonas aeruginosa infection is a serious problem in patients hospitalized with cancer, cystic fibrosis, and burns. The case fatality rate in these patients is near 50 percent (Textbook of Bacteriology). 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 Pseudomonas aeruginosa infection human vaccine Generic Unknown VO_0000393 Inactivated or "killed" vaccine Licensed A generic representation of vaccines developed to prevent Pseudomonas aeruginosa infection in humans, most commonly utilizing inactivated (killed) whole-cell preparations to elicit protective immune responses. Mink Distemper-Enteritis Modified Live & Killed Virus Vaccine-Clostridium Botulinum Type C-Pseudomonas Aeruginosa Bacterin-Toxoid (USDA: 4949.20) Intervet Inc. VO_0001834 Live, attenuated vaccine; Inactivated or "killed" vaccine Licensed USA Mink Distemper-Enteritis Modified Live & Killed Virus Vaccine-Clostridium Botulinum Type C-Pseudomonas Aeruginosa Bacterin-Toxoid (USDA: 4949.31) United Vaccines, Inc. VO_0001835 Live, attenuated vaccine; Inactivated or "killed" vaccine Licensed USA Mink Enteritis Killed Virus Vaccine-Clostridium Botulinum Type C-Pseudomonas Aeruginosa Bacterin-Toxoid (USDA: 49A5.20) Intervet Inc. VO_0001839 Inactivated or "killed" vaccine Licensed USA Mink Enteritis Killed Virus Vaccine-Clostridium Botulinum Type C-Pseudomonas Aeruginosa Bacterin-Toxoid (USDA: 49A5.21) United Vaccines, Inc. VO_0001840 Inactivated or "killed" vaccine Licensed USA P. aeruginosa DNA Vaccine encoding OprF VO_0004189 DNA vaccine Research pVR1020 abdomen gene gun abdomen gene gun The pVR1020/oprF plasmid. DNA vaccine construction The 977-bp oprF gene was cloned from P. aeruginosa PAO1 genomic DNA into the eukaryotic expression plasmid pVR1020 (Price et al., 2001). Pathogen Free ICR At 14-day intervals, groups of 30 mice were inoculated a total of three times in the abdomen via biolistic particle injection (Helios Gene Gun kit; Bio-Rad, Richmond, Calif.) on days 0, 14, and 28 with 2 μg of either pVR1020 (control) or pVR1020/oprF, which was used to coat 1-μm-diameter gold beads (Price et al., 2001). A significant reduction in the presence of severe macroscopic lesions, as well as in the number of bacteria present in the lungs, was seen in immunized mice (Price et al., 2001). Two weeks after the final immunization, the mice were challenged with agar beads containing the P. aeruginosa FD immunotype 4 strain. The mice were first anesthetized with an intraperitoneal injection of sodium pentobarbital and then inoculated via a tracheal incision with 50 μl of an agar bead slurry encasing approximately 7 × 10^2 CFU of P. aeruginosa (Price et al., 2001). The immunoprotective potential of the pVR1020/oprF vaccine was tested in a mouse model of chronic pulmonary infection (Price et al., 2001). P. aeruginosa DNA vaccine pGACAG-OprF/OprI VO_0004570 DNA vaccine Research pGACAG [Ref2701:Saha et al., 2006] intramuscular electroporation intramuscular electroporation DNA vaccine construction DNA vaccine construction VO_0003057 Monovalent DNA vaccination targeting OprF/OprI could protect 80% of mice 4 days p.i. On the other hand, 70% of mice immunized with the control plasmid, PilA vaccine, or multivalent vaccine via GG were dead within 5 days p.i. (p < 0.01) (Saha et al., 2006). P. aeruginosa DNA vaccine pGACAG-OprF/OprI + pGACAG-PcrV + pGACAG-PilA VO_0004572 DNA vaccine Research pGACAG [Ref2701:Saha et al., 2006] intramuscular electroporation intramuscular electroporation DNA vaccine construction DNA vaccine construction DNA vaccine construction DNA vaccine construction VO_0003057 All mice vaccinated with multivalent DNA via imEPT survived for more than 10 days p.i. with PAK. On the other hand, 70% of mice immunized with the control plasmid, PilA vaccine, or multivalent vaccine via GG were dead within 5 days p.i. (p < 0.01) (Saha et al., 2006). P. aeruginosa DNA vaccine pGACAG-PcrV VO_0004571 DNA vaccine Research pGACAG [Ref2701:Saha et al., 2006] intramuscular electroporation intramuscular electroporation DNA vaccine construction VO_0003057 Monovalent DNA vaccination targeting PcrV could protect 80% of mice 4 days p.i. On the other hand, 70% of mice immunized with the control plasmid, PilA vaccine, or multivalent vaccine via GG were dead within 5 days p.i. (p < 0.01) (Saha et al., 2006). P. aeruginosa OprI Protein Vaccine VO_0004190 Subunit vaccine Research Intraperitoneal injection (i.p.) 100 μl of 1.5% Al(OH)3 (Finke et al., 1990). Intraperitoneal injection (i.p.) Recombinant OprI protein Recombinant protein preparation BALB/c Female BALB/c mice, 12 to 16 weeks old, received 100 μl (27 ,ug) of OprI suspended in 100 μl of 1.5% Al(OH)3 intraperitoneally on days 0, 14, 35, and 63. Controls received Al(OH)3 only (Finke et al., 1990). Recombinant OprI protein was used to immunize mice, and was found to be protective against a challenge with a four- to fivefold 50% lethal dose of P. aeruginosa (Finke et al., 1990). mice were challenged intraperitoneally 10 days after the last immunization with 200 μl of a P. aeruginosa serogroup 6 suspension. Mice vaccinated with recombinant OprI received 6 x 10^6 to 1 x 10^8 living organisms each. (Finke et al., 1990). P. aeruginosa PcrV Protein Vaccine VO_0004191 Subunit vaccine Research Intramuscular injection (i.m.) 0.1 ml of incomplete Freund's adjuvant (Holder et al., 2001). Intramuscular injection (i.m.) PcrV Recombinant protein preparation PcrV was produced as a lipopolysaccharide-free histidine-tagged infusion protein in pET16b and was purified by nickel chromatography (Holder et al., 2001). CF-1 On day 0, groups of 10 female CF-1 mice weighing 22 to 25 g were immunized intramuscularly in the hind leg (10 μg of immunogen in 0.1 ml of incomplete Freund's adjuvant), followed by a booster dose (10 μg in saline) without adjuvant on day 14 (Holder et al., 2001). Burned Pseudomonas aeruginosa-infected mice immunized against PcrV, a type III virulence system translocating protein, showed significantly enhanced survival compared to controls (Holder et al., 2001). Using the burned mouse model, mice were challenged by one of three strains of P. aeruginosa (Holder et al., 2001). SL3261-P. aeruginosa serogroup O11 O antigen VO_0004674 Recombinant vector vaccine Research Intramuscular injection (i.m.) Attenuated Salmonella enterica serovar Typhimurium SL3261 expressing P. aeruginosa serogroup O11 O antigen (DiGiandomenico et al., 2004). Intramuscular injection (i.m.) For oral vaccination, mice were fed 100 μl of either PBS or the Salmonella vector and vaccine strains (1 × 10^9 to 5 × 10^9 CFU) by intragastric gavage. Oral inoculation was repeated once per week for a total of 4 weeks. For i.p. vaccination, mice were inoculated with a single dose of either PBS or each Salmonella strain (10^6 CFU) (DiGiandomenico et al., 2004). VO_0003057 Orally vaccinated mice with an O11 strain (9882-80) at 6 and 12 times the 50% lethal dose showed increased survival in mice that received the vaccine compared to phosphate-buffered saline (PBS)- and vector-treated controls; no difference in survival was seen with a heterologous strain, 6294 (serogroup O6). In addition, significant protection against 9882-80 was not observed in i.p. vaccinated animals (DiGiandomenico et al., 2004). Mice were challenged with P. aeruginosa strains 9882-80 (serogroup O11) and 6294 (serogroup O6) (DiGiandomenico et al., 2004). OprF Pseudomonas aeruginosa PAO1 VO_0012360 878442 15596974 PA1777 AE004091 NP_250468 208964 1921173 1922225 + outer membrane porin F 4.75 34266.56 350 >NC_002516.2:1921173-1922225 Pseudomonas aeruginosa PAO1 chromosome, complete genome GATGAAACTGAAGAACACCTTAGGCGTTGTCATCGGCTCGCTGGTTGCCGCTTCGGCAATGAACGCCTTT GCCCAGGGCCAGAACTCGGTAGAGATCGAAGCCTTCGGCAAGCGCTACTTCACCGACAGCGTTCGCAACA TGAAGAACGCGGACCTGTACGGCGGCTCGATCGGTTACTTCCTGACCGACGACGTCGAGCTGGCGCTGTC CTACGGTGAGTACCATGACGTTCGTGGCACCTACGAAACCGGCAACAAGAAGGTCCACGGCAACCTGACC TCCCTGGACGCCATCTACCACTTCGGTACCCCGGGCGTAGGTCTGCGTCCGTACGTGTCGGCTGGTCTGG CTCACCAGAACATCACCAACATCAACAGCGACAGCCAAGGCCGTCAGCAGATGACCATGGCCAACATCGG CGCTGGTCTGAAGTACTACTTCACCGAGAACTTCTTCGCCAAGGCCAGCCTCGACGGCCAGTACGGTCTG GAGAAGCGTGACAACGGTCACCAGGGCGAGTGGATGGCTGGCCTGGGCGTCGGCTTCAACTTCGGTGGTT CGAAAGCCGCTCCGGCTCCGGAACCGGTTGCCGACGTTTGCTCCGACTCCGACAACGACGGCGTTTGCGA CAACGTCGACAAGTGCCCGGATACCCCGGCCAACGTCACCGTTGACGCCAACGGCTGCCCGGCTGTCGCC GAAGTCGTACGCGTACAGCTGGACGTGAAGTTCGACTTCGACAAGTCCAAGGTCAAAGAGAACAGCTACG CTGACATCAAGAACCTGGCTGACTTCATGAAGCAGTACCCGTCCACTTCCACCACCGTTGAAGGTCACAC CGACTCCGTCGGCACCGACGCTTACAACCAGAAGCTGTCCGAGCGTCGTGCCAACGCCGTTCGTGACGTA CTGGTCAACGAGTACGGTGTAGAAGGTGGTCGCGTGAACGCTGTTGGTTACGGCGAGTCCCGCCCGGTTG CCGACAACGCCACCGCTGAAGGCCGCGCTATCAACCGTCGCGTTGAAGCCGAAGTAGAAGCTGAAGCCAA GTA >NP_250468.1 outer membrane porin F [Pseudomonas aeruginosa PAO1] MKLKNTLGVVIGSLVAASAMNAFAQGQNSVEIEAFGKRYFTDSVRNMKNADLYGGSIGYFLTDDVELALS YGEYHDVRGTYETGNKKVHGNLTSLDAIYHFGTPGVGLRPYVSAGLAHQNITNINSDSQGRQQMTMANIG AGLKYYFTENFFAKASLDGQYGLEKRDNGHQGEWMAGLGVGFNFGGSKAAPAPEPVADVCSDSDNDGVCD NVDKCPDTPANVTVDANGCPAVAEVVRVQLDVKFDFDKSKVKENSYADIKNLADFMKQYPSTSTTVEGHT DSVGTDAYNQKLSERRANAVRDVLVNEYGVEGGRVNAVGYGESRPVADNATAEGRAINRRVEAEVEAEAK Protective antigen The oprF gene was cloned into plasmid vector pVR1020, and the plasmid vaccines were delivered to mice by biolistic (gene gun) intradermal inoculation. Following the initial immunization and two consecutive boosts, each at 2-week intervals, protection was demonstrated in a mouse model of chronic pulmonary infection by P. aeruginosa. Eight days postchallenge, both lungs were removed and examined. A significant reduction in the presence of severe macroscopic lesions, as well as in the number of bacteria present in the lungs, was seen [Ref1498:Price et al., 2001]. Our data showed that mice immunized with OprF/OprI or OprF/OprI and flagellin B are significantly protected from infection caused by mucoid and nonmucoid strains of P. aeruginosa.[Ref4793:Hassan et al., 2018]. OprI Pseudomonas aeruginosa PAO1 VO_0012362 879851 15598049 PA2853 AE004091 NP_251543 208964 3206914 3207165 + outer membrane lipoprotein OprI 8.51 8635.98 83 >NC_002516.2:3206914-3207165 Pseudomonas aeruginosa PAO1 chromosome, complete genome GATGAACAACGTTCTGAAATTCTCTGCTCTGGCTCTGGCTGCTGTTCTGGCCACCGGTTGCAGCAGCCAC TCCAAAGAAACCGAAGCTCGTCTGACCGCTACCGAAGACGCAGCTGCTCGTGCTCAGGCTCGCGCTGACG AAGCCTATCGCAAGGCTGACGAAGCTCTGGGCGCTGCTCAGAAAGCTCAGCAGACTGCTGACGAGGCTAA CGAGCGTGCCCTGCGCATGCTGGAAAAAGCCAGCCGCAAGTA >NP_251543.1 outer membrane lipoprotein OprI [Pseudomonas aeruginosa PAO1] MNNVLKFSALALAAVLATGCSSHSKETEARLTATEDAAARAQARADEAYRKADEALGAAQKAQQTADEAN ERALRMLEKASRK Protective antigen Recombinant OprI protein was used to immunize mice, and was found to be protective against a challenge with a four- to fivefold 50% lethal dose of P. aeruginosa [Ref1501:Finke et al., 1990]. Our data showed that mice immunized with OprF/OprI are significantly protected from infection caused by mucoid and nonmucoid strains of P. aeruginosa.[Ref4793:Hassan et al., 2018] PcrV Pseudomonas aeruginosa PAO1 VO_0012361 882997 15596903 PA1706 AE004091 NP_250397 208964 1852287 1853171 + type III secretion protein PcrV 4.77 30496.99 294 >NC_002516.2:1852287-1853171 Pseudomonas aeruginosa PAO1 chromosome, complete genome GATGGAAGTCAGAAACCTTAATGCCGCTCGCGAGCTGTTCCTGGACGAGCTCCTGGCCGCGTCGGCGGCG CCTGCCAGTGCCGAGCAGGAGGAACTGCTGGCCCTGTTGCGCAGCGAGCGGATCGTGCTGGCCCACGCCG GCCAGCCGCTGAGCGAGGCGCAAGTGCTCAAGGCGCTCGCCTGGTTGCTCGCGGCCAATCCGTCCGCGCC TCCGGGGCAGGGCCTCGAGGTACTCCGCGAAGTCCTGCAGGCACGTCGGCAGCCCGGTGCGCAGTGGGAT CTGCGCGAGTTCCTGGTGTCGGCCTATTTCAGCCTGCACGGGCGTCTCGACGAGGATGTCATCGGTGTCT ACAAGGATGTCCTGCAGACCCAGGACGGCAAGCGCAAGGCGCTGCTCGACGAGCTCAAGGCGCTGACCGC GGAGTTGAAGGTCTACAGCGTGATCCAGTCGCAGATCAACGCCGCGCTGTCGGCCAAGCAGGGCATCAGG ATCGACGCTGGCGGTATCGATCTGGTCGACCCCACGCTATATGGCTATGCCGTCGGCGATCCCAGGTGGA AGGACAGCCCCGAGTATGCGCTGCTGAGCAATCTGGATACCTTCAGCGGCAAGCTGTCGATCAAGGATTT TCTCAGCGGCTCGCCGAAGCAGAGCGGGGAACTCAAGGGCCTCAGCGATGAGTACCCCTTCGAGAAGGAC AACAACCCGGTCGGCAATTTCGCCACCACGGTGAGCGACCGCTCGCGTCCGCTGAACGACAAGGTCAACG AGAAGACCACCCTGCTCAACGACACCAGCTCCCGCTACAACTCGGCGGTCGAGGCGCTCAACCGCTTCAT CCAGAAATACGACAGCGTCCTGCGCGACATTCTCAGCGCGATCTA >NP_250397.1 type III secretion protein PcrV [Pseudomonas aeruginosa PAO1] MEVRNLNAARELFLDELLAASAAPASAEQEELLALLRSERIVLAHAGQPLSEAQVLKALAWLLAANPSAP PGQGLEVLREVLQARRQPGAQWDLREFLVSAYFSLHGRLDEDVIGVYKDVLQTQDGKRKALLDELKALTA ELKVYSVIQSQINAALSAKQGIRIDAGGIDLVDPTLYGYAVGDPRWKDSPEYALLSNLDTFSGKLSIKDF LSGSPKQSGELKGLSDEYPFEKDNNPVGNFATTVSDRSRPLNDKVNEKTTLLNDTSSRYNSAVEALNRFI QKYDSVLRDILSAI Protective antigen Burned Pseudomonas aeruginosa-infected mice immunized against PcrV, a type III virulence system translocating protein, showed significantly enhanced survival compared to controls [Ref1499:Holder et al., 2001]. The results clearly show that, with PcrV as the vaccine antigen, all three adjuvants tested, FA, alum and CpG ODN, were effective in inducing protective immunity against infection with P. aeruginosa. [Ref4686:Hamaoka et al., 2017] pilA Pseudomonas aeruginosa PAO1 15599721 CDD:227304 208964 ? type 4 fimbrial protein PilA 6.59 15164.05 225 Tfp pilus assembly protein, major pilin PilA [Cell motility, Extracellular structures]; COG4969 >NP_253215.1 type 4 fimbrial protein PilA [Pseudomonas aeruginosa PAO1] MKAQKGFTLIELMIVVAIIGILAAIAIPQYQNYVARSEGASALATINPLKTTVEESLSRGIAGSKIKIGT TASTATETYVGVEPDANKLGVIAVAIEDSGAGDITFTFQTGTSSPKNATKVITLNRTADGVWACKSTQDP MFTPKGCDN Protective antigen Ahmadi et al., 2012 journal Ahmadi H, Tabaraie B, Maleknia S, Pormirzagholi F, Nejati M, Hedayati MH 2012 6 10 721-726 Journal of infection in developing countries Banadkoki et al., 2016 journal Banadkoki AZ, Keshavarzmehr M, Afshar Z, Aleyasin N, Fatemi MJ, Behrouz B, Hashemi FB 2016 44 5 367-373 Biologicals : journal of the International Association of Biological Standardization Behrouz et al., 2016 journal Behrouz B, Mahdavi M, Amirmozafari N, Fatemi MJ, Irajian G, Bahroudi M, Hashemi FB 2016 Burns : journal of the International Society for Burn Injuries Campodónico et al., 2010 journal Campodónico VL, Llosa NJ, Grout M, Döring G, Maira-Litrán T, Pier GB 2010 78 2 746-755 Infection and immunity Finke et al., 1990 journal Finke M, Duchêne M, Eckhardt A, Domdey H, von Specht BU 1990 58 7 2241-2244 Infection and immunity Hamaoka et al., 2017 journal Hamaoka S, Naito Y, Katoh H, Shimizu M, Kinoshita M, Akiyama K, Kainuma A, Moriyama K, Ishii KJ, Sawa T 2017 61 2 64-74 Microbiology and immunology Hassan et al., 2018 journal Hassan R, El-Naggar W, Abd El-Aziz AM, Shaaban M, Kenawy HI, Ali YM 2018 51 3 312-320 Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi Holder et al., 2001 journal Holder IA, Neely AN, Frank DW 2001 69 9 5908-5910 Infection and immunity Korpi et al., 2015 journal Korpi F, Irajian G, Mahadavi M, Motamedifar M, Mousavi M, Laghaei P, Raei N, Behrouz B 2015 Journal of microbiology and biotechnology Laghaei et al., 2016 journal Laghaei P, Hashemi FB, Irajian G, Korpi F, Amirmozafari N, Behrouz B 2016 74 71-81 Molecular immunology Price et al., 2001 journal Price BM, Galloway DR, Baker NR, Gilleland LB, Staczek J, Gilleland HE Jr 2001 69 5 3510-3515 Infection and immunity Rehm et al., 1994 journal Rehm BH, Grabert E, Hein J, Winkler UK 1994 16 1 43-51 Microbial pathogenesis Saha et al., 2006 journal Saha S, Takeshita F, Sasaki S, Matsuda T, Tanaka T, Tozuka M, Takase K, Matsumoto T, Okuda K, Ishii N, Yamaguchi K, Klinman DM, Xin KQ, Okuda K 2006 24 37-39 6240-6249 Vaccine Salyers and Whitt., 2002 book Abigail A. 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