Virulence role of the outer membrane protein CarO in carbapenem-resistant <i>Acinetobacter baumannii</i>

Labrador-Herrera, Gema; Pérez-Pulido, Antonio J.; Álvarez‐Marín, Rocío; Casimiro-Soriguer, Carlos S.; Cebrero-Cangueiro, Tania; Morán-Barrio, Jorgelina; Pachón, Jerónimo; Viale, Alejandro M.; Pachón-Ibáñez, María Eugenia

doi:10.1080/21505594.2020.1855912

Cited by 20 publications

(15 citation statements)

References 45 publications

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“…CarO is a 29 kDa outer membrane transporter, loss of which has been associated with increased antibiotic resistance (Mussi, Limansky et al 2005, Uppalapati, Sett et al 2020). The role of CarO in phage sensitivity is not clear, but its truncation may lead to other cell wall defects that reduce sensitivity to this phage; truncations in CarO have been associated with reduced adherence and invasion in tissue culture and with reduced virulence in vivo (Labrador-Herrera, Perez-Pulido et al 2020). This finding illustrates that defects in the capsule locus are not the only means by which TP1 may gain phage insensitivity.…”

Section: Resultsmentioning

confidence: 99%

Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy

Liu

Hernandez-Morales²,

Clark

et al. 2021

Preprint

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In 2016, a 68-year-old patient with a disseminated multi-drug resistant Acinetobacter baumannii infection was treated using lytic bacteriophages in one of the first modern human clinical uses of phage therapy in the United States. Due to the emergency nature of the treatment there was little time to thoroughly characterize the phages used in this intervention or the pathogen itself. Here we report the genomes of the nine phages used for treatment and three strains of A. baumannii isolated prior to and during treatment. The eight phages used in the initial treatment were found to be a group of closely related T4-like myophages; the ninth phage, AbTP3Φ1, was found to be an unrelated Fri1-like podophage. Analysis of 19 A. baumannii isolates collected before and during phage treatment showed that resistance to the T4-like phages appeared as early as two days following the start of treatment. Three A. baumannii strains (TP1, TP2 and TP3) collected before and during treatment were sequenced to closure, and all contained a 3.9 Mb chromosome of sequence type 570 with a KL116 capsule locus and identical 8.7 kb plasmids. Phage-insensitive mutants of A. baumannii strain TP1 were generated in vitro and the majority of identified mutations were located in the bacterial capsule locus. The presence of the same mutation in both the in vitro mutants and in phage-insensitive isolates TP2 and TP3, which evolved in vivo during phage treatment, indicate that in vitro investigations can produce results that are relevant and predictive for the in vivo environment.

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Section: Resultsmentioning

confidence: 99%

Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy

Liu

Hernandez-Morales²,

Clark

et al. 2021

Preprint

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show abstract

“…The emergence of multidrug resistance (MDR) A. baumannii is recognized as a serious health concern in hospitals across the world (Savov et al 2019 ). CarO from A. baumannii is a membrane porin that uptake small molecules such as l -ornithine, Carbapenem, and other basic amino acids (Labrador-Herrera et al 2020 ; Tohidinia et al 2020 ). In a study, researchers were demonstrated outer membrane vesicles (OMVs) of A. baumannii had able to induce protective immunity against A. baumannii .…”

Section: Discussionmentioning

confidence: 99%

Design of a Multi-epitope Vaccine Against Acinetobacter baumannii Using Immunoinformatics Approach

Touhidinia

Sefid

Bidakhavidi

2021

Int J Pept Res Ther

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Acinetobacter baumannii is one of the most successful pathogens causing nosocomial infections and has significantly multidrug-resistant. So far, there are no certain treatments to protect against infection with A. baumannii , therefore an effective A. baumannii vaccine needed. The purpose of this study was to predict antigenic epitopes of CarO protein for designing the A. baumannii vaccine using immunoinformatics analysis. CarO protein is one of the most important factors in the resistance against the antibiotic Carbapenem . In this study, T and B-cell epitopes of CarO protein were predicted and screened based on the antigenicity, toxicity, allergenicity features. The epitopes were linked by suitable linkers. Four different adjuvants were attached to the vaccine constructs which among them, vaccine construct 3 was chosen to predict the secondary and the 3D structure of the vaccine. The refinement process was performed to improve the quality of the 3D model structure; the validation process is performed using the Ramachandran plot and ProSA z-score. The designed vaccine's binding affinity to six various HLA molecules and TLR 2 and TLR4 were evaluated by molecular docking. Finally, in silico gene cloning was performed in the pET28a (+) vector. The findings suggest that the vaccine may be a promising vaccine to prevent A. baumannii infection.

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“…CarO, or carbapenem susceptibility protein, was first identified in an A. baumannii strain, where the deletion of the gene encoding a 29 kDa protein conferred resistance to imipenem (Limansky et al, 2002). Several reports thereafter have indicated its role in carbapenem resistance as well as the uptake of amino acids such as ornithine and glycine (Mussi et al, 2007;Labrador-Herrera et al, 2020;Uppalapati et al, 2020). In addition to its possible role in carbapenem resistance, CarO also mediates adhesion and invasion into epithelial cell lines.…”

Section: Virulence and Pathogenesis Factorsmentioning

confidence: 99%

Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infection

Shadan¹,

Pathak

Ying

et al. 2023

Front. Cell. Infect. Microbiol.

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Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infectionAcinetobacter baumannii is a gram-negative multidrug-resistant nosocomial pathogen and a major cause of hospital acquired infetions. Carbapenem resistant A. baumannii has been categorised as a Priority1 critial pathogen by the World Health Organisation. A. baumannii is responsible for infections in hospital settings, clinical sectors, ventilator-associated pneumonia, and bloodstream infections with a mortality rates up to 35%. With the development of advanced genome sequencing, molecular mechanisms of manipulating bacterial genomes, and animal infection studies, it has become more convenient to identify the factors that play a major role in A. baumannii infection and its persistence. In the present review, we have explored the mechanism of infection, virulence factors, and various other factors associated with the pathogenesis of this organism. Additionally, the role of the innate and adaptive immune response, and the current progress in the development of innovative strategies to combat this multidrug-resistant pathogen is also discussed.

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Virulence role of the outer membrane protein CarO in carbapenem-resistant Acinetobacter baumannii

Cited by 20 publications

References 45 publications

Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy

Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy

Design of a Multi-epitope Vaccine Against Acinetobacter baumannii Using Immunoinformatics Approach

Deciphering the virulence factors, regulation, and immune response to Acinetobacter baumannii infection

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