With the emergence and prevalence of multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) clinical isolates, antibiotics are at a disadvantage in the battle against disease-causing microorganisms. Bacteriophages can kill the host efficiently and specifically and are expected to be bactericidal biologics and antibiotic substitutes. With comprehensive knowledge about phage and P. aeruginosa, Creative Biolabs offers support for the development of therapeutic phage against P. aeruginosa.
P. aeruginosa is an encapsulated facultative anaerobic gram-negative bacterium. It is an important soil bacterium with the ability to decompose polycyclic aromatic hydrocarbons, it is also frequently detected in water, animals, and humans. As an opportunistic pathogen, P. aeruginosa is one of the most common bacteria causing nosocomial infections and can cause severe and even fatal acute or chronic infections in individuals with compromised immune systems.
The indiscretion and overuse of antibiotics lead to the spread and accumulation of resistance among P. aeruginosa colonies. P. aeruginosa acquires resistance genes through horizontal gene transfer or self-mutation and achieves drug resistance through efflux pumps, up-regulation of β-lactamase or changes in porins. Carbapenem-resistant P. aeruginosa is one of the key pathogens in the priority pathogen list published by the World Health Organization, as well as a member of ESKAPE pathogens. Well-characterized laboratory strains commonly used in phage-related research are PAO1 and PA14, both of which have assembled publicly available ordered transposon mutation libraries.
Fig.1 Phage-infected Pseudomonas aeruginosa PAO1 strain. (Testa, 2019)
The virulence factors of P. aeruginosa are mainly derived from the biofilms it produces. A biofilm is a protective structure composed of multiple components that surround cells. Biofilm allows bacteria to grow and fight off the host's immune system. The most important components of P. aeruginosa biofilm are exopolysaccharides, including alginate, PSL and PEL, which are responsible for the surface attachment, formation, and stability of biofilms.
Fig.2 Important factors in biofilm production by P. aeruginosa. (Diggle, 2020)
Phages parasitizing P. aeruginosa include Epa4, Epa7, PASA16, vB_PaeM_CEB_DP1, etc. These phages that mainly belong to the Cauroviridae interact with host cells through different yet similar processes. Phages specifically recognize their hosts by lipopolysaccharide, O-specific antigens, or other protein components, and use depolymerases to lyse the bacterial cell wall and inject genetic material into the bacteria. During different stages of phage replication, the phage expresses different gene products to direct and take over the gene expression of bacterial hosts, which results in global changes in the host cell's mRNA and protein. After the new virion is assembled, the virulent phage lyses the bacteria from the inside and releases the progeny phage.
Fig.3 Temporal kinetic profile of phage PaP3 infection after Pseudomonas aeruginosa. (Zhao, 2016)
Although our understanding of the biology of phages and host bacteria is on the rise, the development of phage therapy still requires greater research and understanding, as well as a more comprehensive understanding of the mechanisms of host-phage interactions. With our strong technology platform and cutting-edge theoretical knowledge, professionals at Creative Biolabs provide you strong support in your research and development. Please do not hesitate to contact us for more information.
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