Phage and Acinetobacter baumannii

Acinetobacter baumannii is an opportunistic pathogen, the profile and importance of this pathogen have increased significantly with the increasing incidence and widespread of multidrug-resistant strains. With comprehensive knowledge about phage and Acinetobacter baumannii, Creative Biolabs offers support for the development of therapeutic phage against Acinetobacter baumannii.

Acinetobacter baumannii

Acinetobacter baumannii is an aerobic, non-motile, gram-negative bacillus. It colonizes the skin and causes infection in immunocompromised individuals. Acinetobacter baumannii specifically targets moist tissues, including the respiratory tract, pleural fluid, urinary tract, blood, wounds, nervous system, and eyes. An orange peel and sandpaper-like appearance occur in the initial stages of infection, eventually forming blood vesicles or ruptured hemorrhagic bullae with visible necrotic processes. After invading the human body, Acinetobacter baumannii causes serious nosocomial infections, including pneumonia, meningitis, endocarditis, bacteremia, and sepsis.

Drug Resistance of Acinetobacter baumannii

Acinetobacter baumannii precesses strong drug resistance. The World Health Organization released a list of antibiotic-resistant pathogens that pose a major threat to global public health, and the carbapenem-resistant Acinetobacter baumannii strain ranked first, demonstrating the urgent need for new antimicrobial drugs in the modern medical community. Commonly used Acinetobacter baumannii strains in research include ATCC 17978, ATCC 19606, ACICU (K2), LUH5549 (K32), NIPH146 (K37), and HER1401.

Fig.1 The growth of Acinetobacter baumannii. (Howard, 2012)

Toxicity and Anti-Immune Mechanisms

The virulence potential of Acinetobacter baumannii is manifested through several different pathways, of which the most widely studied is OmpA, a member of the outer membrane protein. OmpA is the most abundant surface protein on Acinetobacter baumannii and also involved in the formation of biofilm and complement resistance, which allows the pathogen to avoid attacking the host immune system and ensures the survival and growth of bacteria in the host. In addition, OmpA, upon binding to host epithelial cells, induces mitochondrial dysfunction and swelling, followed by the release of cytochrome C and the formation of apoptotic bodies.

Phage-Acinetobacter baumannii Interaction

Well-characterized Acinetobacter baumannii phages to date include vB_ApiM_fHyAci03, APK2, APK32, etc.

Fig.2 Annotated phage vB_AbaP_D2 genome map. (Yuan, 2021)

Acinetobacter baumannii produces structurally diverse capsular polysaccharides (CPS) to significantly enhance its survival characteristics, virulence, and drug resistance, but the diverse polysaccharide structure also makes it a prime candidate receptor for phages carrying polysaccharide-degrading enzymes. A specific recombinant depolymerase cleaves the CPS of the phage host by hydrolytic mechanism, rendering the bacterial cell incapable of resisting the ensuing infection process. Acinetobacter baumannii phages often use OpmA, OpmC, lipopolysaccharide, and other antigens to specifically recognize their hosts. Generally, the activity of peptidoglycan-degrading enzymes is restricted by the outer membrane of Gram-negative bacteria. The outer membrane acts as a permeability barrier to idle enzymes into peptidoglycan, so after phage entry into the bacterium and progressively taking over and shutting down host gene expression, some endolysins use a completely independent mechanism of enzymatic activity to lyse the bacterium and release progeny phages.

Fig.3 Plaques formed by different kinds of bacteriophages in Acinetobacter baumannii. (Popova, 2020)

The surge in the scale and level of antibiotic resistance in Acinetobacter baumannii has prompted people to further explore the possibility of phage therapy as an antagonist of bacterial infection. However, its efficacy and safety are inseparable from the reliable isolation, purification, and comprehensive analysis of phages characterization. To help address the threat from this pathogen, Creative Biolabs offers academic knowledge and strong support for the development of phage-based therapies against Acinetobacter baumannii. Please do not hesitate to contact us for more information.

References:

1. Howard, A.; et al. Acinetobacter baumannii: An emerging opportunistic pathogen. Virulence. 2012, 3(3): 243-250.
2. Yuan, Y.; et al. The endolysin of the Acinetobacter baumannii phage vB_AbaP_D2 shows broad antibacterial activity. Microbial Biotechnology. 2021, 14(2): 403-418.
3. Popova, A.V.; et al. Specific interaction of novel Friunavirus phages encoding tail spike depolymerases with corresponding Acinetobacter baumannii capsular types. Journal of Virology. 2020, 95: e1714-1720.