Evaluation of the Trimeric Autotransporter Ata as a Vaccine Candidate against Acinetobacter baumannii Infections

被引:115
作者
Bentancor, Leticia V. [1 ]
Routray, Abhisek [1 ]
Bozkurt-Guzel, Cagla [1 ]
Camacho-Peiro, Ana [1 ]
Pier, Gerald B. [1 ]
Maira-Litran, Tomas [1 ]
机构
[1] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Dept Med,Med Sch, Boston, MA 02115 USA
关键词
ENVIRONMENTAL CONTAMINATION; PSEUDOMONAS-AERUGINOSA; ATTRIBUTABLE MORTALITY; PROTECTIVE IMMUNITY; RESISTANCE GENES; IN-VITRO; OUTBREAK; COLONIZATION; PNEUMONIA; VIRULENCE;
D O I
10.1128/IAI.06096-11
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Acinetobacter baumannii is a multidrug-resistant (MDR) nosocomial pathogen for which immunotherapeutic alternatives are needed. We previously identified a surface autotransporter of A. baumannii, Ata, that bound to various extracellular matrix/basal membrane proteins and was required for full virulence, biofilm formation, and the adhesion of A. baumannii to collagen type IV. We show here that Ata binding to collagen type IV was inhibited by antibodies to Ata. In addition, in the presence of complement and polymorphonuclear cells (PMNs), antibodies to Ata were highly opsonic against A. baumannii ATCC 17978 and showed low to moderate killing activity against four heterologous A. baumannii strains, whereas in the absence of PMNs, antibody to Ata efficiently promoted complement-dependent bactericidal killing of all of the tested A. baumannii isolates. Using a pneumonia model of infection in both immunocompetent and immunocompromised mice, we found that, compared to normal rabbit sera, antisera to Ata significantly reduced the levels of A. baumannii ATCC 17978 and two MDR strains in the lungs of infected mice. The ability of Ata to engender anti-adhesive, bactericidal, opsonophagocytic, and protective antibodies validates its potential use as an antigenic target against MDR A. baumannii infections.
引用
收藏
页码:3381 / 3388
页数:8
相关论文
共 41 条
[1]   Environmental contamination during a carbapenem-resistant Acinetobacter baumannii outbreak in an intensive care unit [J].
Aygün, G ;
Demirkiran, O ;
Utku, T ;
Mete, B ;
Ürkmez, S ;
Yilmaz, M ;
Yasar, H ;
Dikmen, Y ;
Öztürk, R .
JOURNAL OF HOSPITAL INFECTION, 2002, 52 (04) :259-262
[2]   Identification of Ata, a Multifunctional Trimeric Autotransporter of Acinetobacter baumannii [J].
Bentancor, Leticia V. ;
Camacho-Peiro, Ana ;
Bozkurt-Guzel, Cagla ;
Pier, Gerald B. ;
Maira-Litran, Tomas .
JOURNAL OF BACTERIOLOGY, 2012, 194 (15) :3950-3960
[3]   Poly-N-Acetyl-β-(1-6)-Glucosamine Is a Target for Protective Immunity against Acinetobacter baumannii Infections [J].
Bentancor, Leticia V. ;
O'Malley, Jennifer M. ;
Bozkurt-Guzel, Cagla ;
Pier, Gerald B. ;
Maira-Litran, Tomas .
INFECTION AND IMMUNITY, 2012, 80 (02) :651-656
[4]   Evaluation of Flagella and Flagellin of Pseudomonas aeruginosa as Vaccines [J].
Campodonico, Victoria L. ;
Llosa, Nicolas J. ;
Grout, Martha ;
Doering, Gerd ;
Maira-Litran, Tomas ;
Pier, Gerald B. .
INFECTION AND IMMUNITY, 2010, 78 (02) :746-755
[5]   Selection of colistin-resistant Acinetobacter baumannii isolates in postneurosurgical meningitis in an intensive care unit with high presence of heteroresistance to colistin [J].
Carlos Hernan, Rodriguez ;
Karina, Bombicino ;
Gabriela, Granados ;
Marcela, Nastro ;
Carlos, Vay ;
Angela, Famiglietti .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2009, 65 (02) :188-191
[6]   Survival of Acinetobacter baumannii on bed rails during an outbreak and during sporadic cases [J].
Catalano, M ;
Quelle, LS ;
Jeric, PE ;
Di Martino, A ;
Maimone, SM .
JOURNAL OF HOSPITAL INFECTION, 1999, 42 (01) :27-35
[7]   Mechanisms of resistance to ciprofloxacin, ampicillin/sulbactam and imipenem in Acinetobacter baumannii clinical isolates in Taiwan [J].
Chiu, Cheng-Hsun ;
Lee, Hao-Yuan ;
Tseng, Li-Yun ;
Chen, Chyi-Liang ;
Chia, Ju-Hsin ;
Sud, Lin-Hui ;
Liu, Shu-Ying .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2010, 35 (04) :382-386
[8]   The pgaABCD Locus of Acinetobacter baumannii Encodes the Production of Poly-β-1-6-N-Acetylglucosamine, Which Is Critical for Biofilm Formation [J].
Choi, Alexis H. K. ;
Slamti, Leyla ;
Avci, Fikri Y. ;
Pier, Gerald B. ;
Maira-Litran, Tomas .
JOURNAL OF BACTERIOLOGY, 2009, 191 (19) :5953-5963
[9]   Repurposing FDA-approved drugs to combat drug-resistant Acinetobacter baumannii [J].
Chopra, Sidharth ;
Torres-Ortiz, Maria ;
Hokama, Leslie ;
Madrid, Peter ;
Tanga, Mary ;
Mortelmans, Kristien ;
Kodukula, Krishna ;
Galande, Amit K. .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2010, 65 (12) :2598-2601
[10]   Multidrug-resistant Acinetobacter extremity infections in soldiers [J].
Davis, KA ;
Moran, KA ;
McAllister, CK ;
Gray, PJ .
EMERGING INFECTIOUS DISEASES, 2005, 11 (08) :1218-1224